Cancer Biomarkers - Volume 15, issue 4

Authors: Bansal, Navneeta | Gupta, Ashish | Sankhwar, Satya Narain

Article Type: Research Article

Abstract: Urinary bladder cancer (BC) is fifth most common cancer worldwide; the diagnostic methods are mostly instrumental approaches including cystoscopy and cytology. Since BC recurrence rate is high, consequently requires long-term follow-up. The molecular assays that can precisely identify BC at an early stage are obligatory. Although several noninvasive urine and blood samples based biomarkers have been proposed in the last decade but only few have been approved by Food and drug administration (FDA) for clinical purpose. Hence the search for more suitable biomarker is still on. In this review, we summarize the urine and blood based metabolic and protein tests …not only for determination but also BC patient surveillance. Show more

Keywords: Bladder cancer, metabolomics, proteomics, FDA

DOI: 10.3233/CBM-150479

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 339-348, 2015

Authors: Sankhwar, Monica | Sankhwar, Satya Narayan | Abhishek, Amar | Rajender, Singh

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the correlation of Vascular Endothelial Growth Factor (VEGF) and micro-vessel density (MVD) with urinary bladder tumor and its stage. MATERIAL AND METHODS: The study was conducted between January 2010 and December 2012. The study included screening of 122 patients at elevated risk for bladder cancer, of which 35 patients were finally enrolled in the study. Diagnosis was made on the basis of urine cytology, radiological investigation (ultrasound KUB, and CT-scan) and histopathology. Thirty-five normal cancer-free individuals were enrolled as controls. Human VEGF levels were measured using an enzyme linked immunoassay and protein content …(pg/mg protein) by Lowry method. SPSS for Windows version 10.0.7 (SPSS, Chicago, IL, USA) was used for statistical analysis of the data. RESULTS: Mean urine VEGF level in the cases was significantly higher in comparison to the control group. There was a direct correlation between VEGF level and tumor stage. Mean urine VEGF values were minimum in the control group (22.75 ± 15.41 pg/mg creatinine) and maximum in stage IV patients (180.15 ± 75.93 pg/mg creatinine). Tissue VEGF levels also showed a similar trend of increase with increase in stage. Urine VEGF level also showed a correlation with tissue VEGF level. Similarly, MVD showed a significant increase with increase in tumor stage. DISCUSSION: A correlation between bladder cancer and MVD and VEGF suggest that the latter can serve as markers for therapeutic guidance. This is the first study from India on clinical and pathological correlation among urine VEGF, tumor tissue VEGF levels, and Micro Vessel Density (MVD) in urinary bladder cancer patients. Show more

Keywords: Angiogenesis, MVD, urinary bladder cancer, urothelial carcinoma, VEGF

DOI: 10.3233/CBM-150478

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 349-355, 2015

Authors: Nakashima, Masakazu | Matsui, Yoshiyuki | Kobayashi, Takashi | Saito, Ryoichi | Hatahira, Satoko | Kawakami, Kazumi | Nakamura, Eijiro | Nishiyama, Hiroyuki | Ogawa, Osamu

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: To clarify the clinical usefulness and diagnostic accuracy of urine chemokine (C-X-C motif) ligand 1 (CXCL1) as a biomarker for tumor detection and outcome prediction in patients with bladder cancer (BCa). METHODS: We …measured urine CXCL1 levels in 175 patients with BCa and 30 healthy controls. The value of urine CXCL1 concentration normalized by urine creatinine (CXCL1/Cre) was analyzed in terms of detecting bladder tumors and predicting intravesical recurrence after transurethral resection (TUR). RESULTS: CXCL1/Cre was significantly higher (3-fold) in BCa patients than in healthy participants and the difference from control samples was greater in patients with advanced BCa. Although the urine cytology test generally lost diagnostic power in patients with low-grade superficial tumors, the sensitivity of CXCL1/Cre was not compromised in this patient population. Patients with higher CXCL1/Cre were significantly more likely to develop intravesical recurrence after TUR and multivariate analysis identified CXCL1/Cre as an independent predictor of post-TUR intravesical recurrence. Importantly, CXCL1/Cre could successfully classify the probabilities of post-TUR recurrence among patients with intermediate-risk according to EORTC risk criteria into two groups equivalent to its high- and low-risk groups. CONCLUSIONS: Urine CXCL1 is a promising, non-invasive molecular marker for tumor detection and outcome prediction in patients with BCa. Show more

Keywords: Bladder cancer, urine biomarker, sensitivity and specificity, detection, prognostic factor

DOI: 10.3233/CBM-150472

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 357-364, 2015

Authors: Yanagisawa, Nobuyuki | Satoh, Takefumi | Hana, Kiyomi | Ichinoe, Masaaki | Nakada, Norihiro | Endou, Hitoshi | Okayasu, Isao | Murakumo, Yoshiki

Article Type: Research Article

Abstract: BACKGROUND: Oncocytic L-amino acid transporter (LAT) 1 could be a target of new molecular therapy against malignancies. OBJECTIVE: To assess the correlation between overexpression of LAT1 and local progression (LP) in prostatic carcinoma (PC) patients under expectant management (EM). METHODS: This retrospective study analyzed 109 patients with PC who received EM from 1991 to 2006. The expression of LAT1, LAT2, and CD98, as well as Ki-67 labeling indices (LI), was analyzed immunohistochemically in first biopsy or TUR samples diagnosed as adenocarcinomas. RESULTS: Of the 109 patients, 44 (40%) showed LP on clinical …examinations, whereas 65 showed stable disease (SD). LAT1 score and intensity were significantly higher in the LP than in the SD group, as well as among Gleason score (GS)-low (GS < 7) patients who were associated with low-risk. When the LP group was subdivided by D'Amico risk category (low-, intermediate- and high-risk groups), each showed higher LAT1 expression than the SD group. LAT1 expression did not correlate with GS or Ki-67 LI. CONCLUSIONS: Independently of GS, aberrant overexpression of LAT1 in prostatic adenocarcinoma could predict LP under EM. Although prostate biopsy samples are small, LAT1 may be a novel prognostic biomarker of LP. Show more

Keywords: Prostatic carcinoma, L-type amino acid transporter 1, immunohistochemistry, expectant management, prognosis

DOI: 10.3233/CBM-150486

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 365-374, 2015

Authors: Li, Yan-Sen | Chen, Yue-Zhi | Guo, Xiao-Bo | Liu, Xin | Li, Le-Ping

Article Type: Research Article

Abstract: BACKGROUND: Vezatin is an transmembrane protein associated with cell-cell adhesion junctions. In our previous studies, we found that the tumor suppressor function of VEZT was related to methylation of CpG island and were down-regulated in tumor tissue and cells compared to normal controls. However, the role of VEZT gene as a novel putative tumor suppressor in biological characteristics and the relationship with clinicopathological factors and prognosis of gastric cancer was not yet clear. Therefore, we sought to explore these questions and prepare for further research in this study. METHODS: We examined the vezatin expression levels in …119 gastric cancer tissues and adjacent normal tissues by immunohistochemistry. Furthermore, we evaluated the expression of VEZT and its relationship with clinicopathological factors, lymphatic metastasis and prognostic value for gastric cancer. RESULTS: The expression of VEZT was significantly down-regulated in gastric cancer tissues and cell lines and its expression levels was related to differentiation, TNM staging and lymphatic metastasis. Furthermore, analysis of 5-year survival of 119 gastric cancer patients showed that those with strong vezatin expression had significantly longer overall survival time than those with negative vezatin expression. CONCLUSIONS: These data provided an innovative insight that up-regulation of vezatin can be taken as a meaningful way for treating human gastric and other types of cancers. And VEZT expression levels can be considered as a biomarker for gastric cancer progression, lymphatic metastasis and as a novel independent prognostic factor. Show more

Keywords: VEZT, gastric cancer, clinicopathological, lymphatic metastasis, prognosis

DOI: 10.3233/CBM-150476

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 375-380, 2015

Authors: Jiang, Zhaojing | Song, Qiancheng | Yang, Suoping | Zeng, Rong | Li, Xufeng | Jiang, Chunyu | Ding, Weimin | Zhang, Jiren | Zheng, Yanfang

Article Type: Research Article

Abstract: BACKGROUND: Several studies demonstrated that microRNAs are stably detectable in plasma/serum and are potential biomarkers for some diseases. The expression of microRNA-218 (miR-218) is downregulated in esophageal cancer as reported in previous research. OBJECTIVE: The purpose of this study is to investigate whether miR-218 can be served as a serum biomarker for esophageal cancer. METHODS: We tested the expression level of miR-218 in serum of 106 patients with esophageal cancer and 60 healthy volunteers by RT-PCR and analyzed the relationship between serum miR-218 expression and the clinical characteristics. RESULTS: The serum expression …of miR-218 was significantly lower in patients with esophageal cancer than that in healthy individuals. The value of the area under the receiver-operating characteristic (ROC) curve (AUC) was 0.833. Furthermore, the ROC curves to detect early esophageal cancer with Tis-T1 or Stage 0-I showed AUCs of 0.825 and 0.829, respectively. In the esophageal cancer group, the serum expression of miR-218 was found to be lower in esophageal cancer patients with poorer differentiation, later stage, and lymph node metastasis, highlighting that low serum expression of miR-218 may be related to tumor development and progression in esophageal cancer. CONCLUSIONS: The serum expression of miR-218 is downregulated in esophageal cancer patients and is correlated with tumor differentiation, stage, and lymph node metastasis. Serum miR-218 may be a potential biomarker for early detection and clinical evaluation in patient with esophageal cancer. Show more

Keywords: Esophageal cancer, microRNA, microRNA-218, serum biomarker, cancer detection

DOI: 10.3233/CBM-150480

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 381-389, 2015

Authors: Sun, Pengda | Sun, Dong | Wang, Xudong | Liu, Tianzhou | Ma, Zhiming | Duan, Liwei

Article Type: Research Article

Abstract: This article has been retracted, and the online PDF has been watermarked “RETRACTION”. A retraction notice is available at doi: 10.3233/CBM239005.

Keywords: miR-206, colorectal cancer, prognosis, cell growth and invasion

DOI: 10.3233/CBM-150489

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 391-396, 2015

Authors: Parsafar, Soha | Hematti, Simin | Ghorbani, Fateme | Safari, Forousan | Tavassoli, Manoochehr

Article Type: Research Article

Abstract: BACKGROUND: Activated PI3K generate PIP3 to trigger different signaling pathways which regulate a number of cellular functions including cell survival, apoptosis, proliferation and motility. Mutations in many cancers were discovered in the gene encoding the PI3K catalytic subunit, PIK3CA . OBJECTIVE: To date, there has been no report on the association between polymorphism of PIK3CA gene microsatellites and risk of colorectal cancer. In this study, we investigate the relation between the GT dinucleotide repeat in intron 1 of the PIK3CA gene and colorectal cancer risk. METHODS: A case-control study of 103 colorectal …cancer patients and 150 controls was conducted in Iranian people. RESULTS: The results of our study demonstrate that PIK3CA gene allele distribution in Iranian population varies between 13 and 20 repeats. Here we demonstrate that individuals who carry alleles shorter than 17 GT repeat are at higher risk of developing colorectal cancer (OR = 4.0, p= 0), by contrast, those individuals with two alleles longer than 16 GT repeats are at a significantly lower risk of developing colorectal cancer (OR = 0.12, p= 0). CONCLUSION: This result suggests polymorphic GT repeat of PIK3CA gene may be a potential predictive marker of colorectal cancer risk in Iranian population. Show more

Keywords: Colorectal cancer, PIK3CA, GT repeat, polymorphism

DOI: 10.3233/CBM-150487

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 397-403, 2015

Authors: Kilic, Leyla | Yildiz, Ibrahim | Sen, Fatma Karagoz | Erdem, Mustafa Genco | Serilmez, Murat | Keskin, Serkan | Ciftci, Rumeysa | Karabulut, Senem | Ordu, Cetin | Duranyildiz, Derya | Tas, Faruk

Article Type: Research Article

Abstract: BACKGROUND: The aim of this study is to evaluate the correlation of coagulation tests with various clinicopathological variables and tumor markers among colorectal cancer (CRC) patients. MATERIALS AND METHODS: Ninety-four CRC patients were included for evaluation of clinicopathological factors, coagulation assays and tumor marker levels. RESULTS: Metastatic disease was related with elevated INR (p= 0.03). Stage III patients had higher D-dimer values compared with stage II patients (p= 0.03). Correlation of tumor markers indicated a tendency towards elevated D-dimer levels for CEA values higher than median (p= 0.01). High CA 19-9 levels were also …associated with higher INR (p= 0.007). Elderly age, distant metastasis, high CEA, CA-19-9 and LDH levels were associated with poorer overall-survival. CEA level was the only independent prognostic factor in multivariate analysis. CONCLUSIONS: Coagulation assays can be utilized as predictors of disease extent in CRC. Elevated D-dimer and INR values may indicate higher disease stage. Correlation of D-dimer levels with CEA supports their value for assessing tumor burden. Show more

Keywords: Tumor marker, coagulation, colon cancer, D-dimer, CEA, CA 19-9

DOI: 10.3233/CBM-150477

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 405-411, 2015

Authors: Kabzinski, Jacek | Przybylowska, Karolina | Dziki, Lukasz | Dziki, Adam | Majsterek, Ireneusz

Article Type: Research Article

Abstract: Aim of this study was to analyze the correlation between polymorphisms of ERCC2 and ERCC5 genes and efficiency of repair of oxidative DNA damage with the risk of colorectal cancer (CRC). Experimental material was peripheral blood and tumor slices from CRC collected from 235 patients, 240 people without any cancer were control group. Distribution of polymorphisms of ERCC2 and ERCC5 genes in patients with CRC and healthy subjects, as well as level of oxidative DNA damage in patients and in healthy controls was performed. It has been found that the genotype 751Gln/Gln and allele Gln of ERCC2 gene and allele …Asp of 312Asn/Asp polymorphism of ERCC2 gene may be associated with an increased risk of colorectal cancer. Reduced DNA repair efficiency was also demonstrated, which can confirm the important role of oxidative damage and polymorphisms of ERCC2 and ERCC5 genes in the pathogenesis of CRC. In summary, it is critical to establish a link between gene polymorphisms in repair of oxidative DNA damage with the risk of cancer. This in future will allow for diagnostic tests which will let to identify persons with high risk of developing cancer and thus effectively implement prophylactic treatment. Show more

Keywords: Colorectal cancer, polymorphisms, ERCC2, ERCC5, NER, oxidative DNA damage

DOI: 10.3233/CBM-150488

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 413-423, 2015

Authors: Tian, Tian | Gu, Xiaobin | Zhang, Bo | Liu, Yang | Yuan, Chao | Shao, Lijuan | Guo, Yajun | Fan, Kexing

Article Type: Research Article

Abstract: BACKGROUND: High expression of CD14(+)HLA-DR-/low myeloid-derived suppressor cells (MDSCs) is correlated with immunosuppressive activity in various cancers, however, no studies have shown a correlation of these immunosuppressive cells with clinical outcomes in small-cell lung cancer (SCLC) patients. OBJECTIVE: The purpose of the study was to investigate the number, frequency and clinical significance of CD14(+)HLA-DR-/low MDSCs in SCLC patients. METHODS: The peripheral blood of 42 patients with SCLC and 37 healthy controls was analyzed by using flow cytometry. The relationships between the number and frequency of MDSCs, clinicopathological features and overall survival(OS) were analyzed. …The prognostic value of MDSCs was tested by using univariate and multivariate analysis. RESULTS: Our results demonstrated that number and frequency of peripheral CD14(+)HLA-DR-/low MDSCs were significantly increased in SCLC patients than in controls (p< 0.0001 and p< 0.0001, respectively). The frequency of MDSCs correlated with tumor stage (p= 0.02), serum LDH levels (p= 0.001) and with the poorer OS (log-rank test, p= 0.017). Univariate and multivariate analyses suggested that frequency of CD14(+)HLA-DR-/low MDSCs as an independent biomarker for poor prognosis in SCLC patients during follow-up. Our study provides the first evidence that the frequency of CD14(+)HLA-DR-/low MDSCs negatively correlates with clinical outcomes in SCLC patients. CONCLUSIONS: The frequency of CD14(+)HLA-DR-/low MDSCs could be considered as a poor prognostic predictor in SCLC and the elimination of MDSCs during medical interventions may improve the prognosis of SCLC patients. Show more

Keywords: Small-cell lung cancer, myeloid-derived suppressor cells, prognosis, biomarker

DOI: 10.3233/CBM-150473

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 425-432, 2015

Authors: Hiura, Kazuya | Shiraishi, Akiko | Suzuki, Chinami | Takamura, Kei | Yamamoto, Makoto | Komori, Hitoshi | Watanabe, Yasuhiro | Iwaki-Egawa, Sachiko

Article Type: Research Article

Abstract: BACKGROUND: Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), which is a key regulator of tumor angiogenesis. OBJECTIVE: To evaluate biomarkers to predict the benefit of paclitaxel and carboplatin plus bevacizumab (PCB) therapy in patients with advanced or recurrent non-squamous non-small cell lung cancer. METHODS: Among 21 patients treated with PCB, 10 were included in the good responder group and 11 in the non-responder group. Serum VEGF, MMP-2 and MMP-9 were measured using ELISA. RESULTS: There were no significant differences in these markers levels between groups. However, …the good responder group showed a significantly higher pre-treatment MMP-9/ absolute neutrophil count (ANC) score than the non-responder group before the treatment (p= 0.014), and there was a positive correlation between the score and the tumor reduction rate (r= 0.57, p= 0.016). Furthermore, by dividing patients into a high scoring group (MMP-9/ANC ≥ median, n= 11) and a low scoring group (MMP-9/ANC < median, n= 10), former group showed a significant improvement in the median progression-free survival compared with latter group (636 vs. 196 days, p = 0.032). CONCLUSIONS: MMP-9/ANC score before PCB treatment may be a suitable biomarker to assess the anti-tumor effects of PCB therapy. Show more

Keywords: Absolute neutrophil count, matrix metalloproteinase-9, progression-free survival, tumor reduction rate, VEGF

DOI: 10.3233/CBM-150483

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 433-440, 2015

Authors: Abdel Salam, R. | El-Badry, N. | Rizk, A. | El-Sedfy, A. | Kamel, N. | El-Abd, E.

Article Type: Research Article

Abstract: BACKGROUND: Thyroid nodules require pre-surgical cytological assessment for possible risk of malignancy. Many techniques were introduced to enhance differential diagnosis and to avoid unnecessary diagnostic surgery. OBJECTIVE: The study aims to investigate the potential use of ECM1 gene and MMP-2 protein as preoperative tumor markers in suspicious follicular thyroid lesions. METHODS: The study included 40 Egyptian cases with solitary thyroid nodules. They underwent preoperative FNAB followed by thyroidectomy. MMP-2 protein and ECM1 gene were detected using immunostaining and conventional semi-quantitative RT-PCR techniques; respectively. The diagnostic accuracy of FNAB, gene and protein expression level cutoffs …was calculated by using ROC. RESULTS: Both MMP-2 protein and ECM1 gene expressions were significantly higher in malignant than benign group (P < 0.001). Both were significantly higher in higher tumor stages (PMMP-2 = 0.002; PECM1 = 0.032) but only ECM1 significantly differed with tumor size (P < 0.006). The diagnostic performances of ECM1 expression scores was significantly better than that of FNAB (P = 0.049). A significant direct correlation was detected between ECM1 gene and MMP-2 protein expressions in cases of FVPC and of FC (P = 0.014). CONCLUSIONS: MMP-2 protein and ECM1 gene are useful preoperative markers for defining malignancy in suspicious thyroid nodules. Show more

Keywords: ECM1 (Extracellular matrix protein 1), FNAB (fine needle aspiration biopsy), immunostaining, MMP-2 (Matrix metalloproteinase-2), RT-PCR (reverse transcriptase-polymerase chain reaction), thyroid nodules

DOI: 10.3233/CBM-150481

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 441-458, 2015

Authors: Khan, Mosin S. | Pandith, Arshad A. | Masoodi, Shariq R. | Khan, Shoukat H. | Rather, Tanveer A. | Andrabi, Khursid I. | Mudassar, Syed

Article Type: Research Article

Abstract: BACKGROUND: Among various polymorphic variants of TP53 gene, codon 72 polymorphism (Arg72Pro) has been found to be associated with cancer susceptibility, but only few studies have investigated their effect on thyroid cancer risk. OBJECTIVE: A case control study was conducted to elucidate the possible role of this SNP as risk factor in thyroid cancer development and to examine its correlation with various clinicopathological variables. METHODS: In this study, we tested the genotype distribution by PCR-RFLP in 140 thyroid cancer patients and 200 cancer-free controls from Kashmir Valley. RESULTS: Genotype frequencies of …Arg/Arg (GG), Arg/Pro (GC), and Pro/Pro (CC) genotypes among cases were 0.286, 0.343 and 0.371 while in controls 0.45, 0.37 and 0.18 respectively. Proline allele frequency was significantly higher than arginine frequency in patient group (OR = 2.06, 95% C.I = 1.5-2.8). Significant association was found between variant genotype of codon 72 of TP53 gene and young age group, female gender, urban dwellers, non-smokers and patients with elevated TSH levels (P < 0.05). CONCLUSION: It is evident from our study that Arg72Pro SNP of TP53 gene is connected with higher susceptibility to thyroid cancer especially in young age group, female gender, non-smokers and patients with elevated TSH levels, hence, implicated in thyroid carcinogenesis. Show more

Keywords: Papillary thyroid cancer, thyroid stimulating hormone, benign thyroid disease, differentiated thyroid cancer, polymerase chain reaction, restriction digestion

DOI: 10.3233/CBM-150485

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 459-465, 2015

Authors: Chen, Zhanwei | Wu, Haiwei | Huang, Shengyun | Li, Wengang | Zhang, Shizhou | Zheng, Peihui | Zhou, Xiaoqing | Liu, Wenlei | Zhang, Dongsheng

Article Type: Research Article

Abstract: BACKGROUND: The expression of Bcl-2/adenovirus E1B 19 kDa-interacting protein3 (BNIP3) has been explored in many human malignancies, but not in adenoid cystic carcinoma (ACC). OBJECTIVE: This study investigated the clinical significance of expression of BNIP3 in ACC tissues and cells and elucidated its correlations to hypoxia-induced autophagy. METHODS: Immunohistochemical and immunofluorescence staining were used to explore BNIP3, HIF-1α and LC3 expression. RESULTS: BNIP3 was positively expressed in 41 cases (63.1%), and was significantly correlated with histological grade (P= 0.001). HIF-1α was positively expressed in 52 cases (80.0%) and was significantly …correlated with TNM stage (P= 0.023) and histological grade (P= 0.024). LC3 was positively expressed in 37 cases (56.9%) and was significantly correlated with TNM stage (P= 0.019). The expression of BNIP3 was correlated with HIF-1α expression (P= 0.011). The overall survival in the negative BNIP3 expression group tended to be better than in the positive BNIP3 expression (P= 0.011). In vitro experiment, BNIP3 immunofluorescence staining was detected in cells treated with CoCl2 (for hypoxic condition). CONCLUSIONS: The data indicated that BNIP3 plays a vital role in the tumorigenesis of adenoid cystic carcinoma and could be a new target for gene therapy of adenoid cystic carcinoma. Show more

Keywords: Adenoid cystic carcinoma, hypoxia, BNIP3, HIF-1α, autophagy

DOI: 10.3233/CBM-150474

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 467-475, 2015

Authors: Ouyang, Huoniu | Guo, Zhilin | Cheng, Zhihua | Guo, Yu

Article Type: Research Article

Abstract: BACKGROUND: Glioma is one of the most common primary malignant brain tumors. However, the potential molecular mechanism of glioma tumorigenesis is limited. In this study, we aimed to investigate the functional relationship between glioma and a potential tumor related gene JUB . METHODS: Lentivirus-based RNA interference was carried out to knock down JUB expression in human glioma cells U251. The effects of JUB on cell proliferation and cell cycle were detected by MTT, colony formation and flow cytometry assays. RESULTS: Lentivirus-mediated shRNA could effectively suppress JUB expression in …U251 cells, resulting in significant decreases in cell proliferation and colony formation. Flow cytometry analysis showed that JUB silencing blocked cell cycle at S and G2/M phases, and induced apoptosis, which could contribute to cell growth suppression. Furthermore, knockdown of JUB caused downregulation of CDK6 and activations of Caspase 3 and PARP. CONCLUSIONS: The results in this study uncovered that JUB was a regulator involved in proliferation of glioma cells, and it could be used as a potential therapeutic target for glioma. Show more

Keywords: Glioblastomas, JUB, proliferation, RNA interference, ajuba LIM protein

DOI: 10.3233/CBM-150491

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 477-484, 2015

Authors: Nuerrula, Yiliyaer | Rexiati, Mulati | Liu, Qiang | Wang, Yu-Jie

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: Looking for tumor markers by using protein chip technology is one of the hot topics, but many studies are still limited on short term detection of differential expressed proteins before and after surgery among patients with RCC. This study analyzed differential expressed serum protein and its clinical significance with clear-cell renal cell carcinoma to further measurement of the rule of variable expressing. METHODS: Eighty-nine patients with clear-cell renal cell carcinoma who underwent surgery from November 2013 to 2014 and postoperatively confirmed by pathology were entered in RCC group, 100 healthy volunteers and patients …without RCC who underwent medical examination in the same period were entered in control group. The serum protein were analyzed in both group before surgery and every regular follow-up period in 1 year after surgery with RCC group. The surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS) and weak cation exchange protein chip (CM10) technology systems were used for identifying differential expressed serum protein in RCC group and controls. The linear support vector machine (SVM) was applied to establish the diagnostic model of protein fingerprints and the leave-one-out cross validation was used for determining model discriminating effect. The differential expressed proteins were analyzed by ZUCI-PDAS protein spectral data analysis system. RESULTS: Five kinds of proteins were identified as potential biomarker, ultimately. The M/Z of these proteins was 15953, 7987, 9304, 8948, 5911, respectively. There were significant difference on expression level of these proteins with two groups preoperatively (P< 0.05). Comparison of all postoperative expression levels to preoperative one and each differential level mutually between a year in postoperative period also revealed statistical significance (P< 0.05). With taking identified proteins as biomarker, the sensitivity and specificity in predicting clear-cell renal cell carcinoma was 88.8% (79/89) and 91.0% (91/100), respectively. CONCLUSION: The corresponding specific protein was Bcl-2 family apoptosis regulatory proteins, WAP four-disulfide core protein, Krueppel-like factor 8, monocyte chemotactic protein-1, serum amyloid β -protein-4, respectively, and will may serve as tumor markers of kidney cancer. These proteins manifests high predictive value for clear-cell renal cell carcinoma, and may contribute to therapeutic evaluation, prognosis and targeted therapy for clear-cell renal cell carcinoma. Show more

Keywords: Clear cell renal cell carcinoma, proteomics, tumor marker, expression

DOI: 10.3233/CBM-150490

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 485-491, 2015

Authors: Yoshimoto, Chiharu | Iwabuchi, Takuya | Shigetomi, Hiroshi | Kobayashi, Hiroshi

Article Type: Research Article

Abstract: OBJECTIVE: The purpose of this study was to investigate cyst fluid levels of total iron, heme iron and free iron in benign endometriotic cysts and endometriosis-associated ovarian cancer (EAOC) and to demonstrate the significance of these biomarkers in differential diagnosis between EAOC and endometriotic cysts. METHODS: Cyst fluid samples were obtained from eleven patients with EAOC and thirty-six women with benign endometriotic cysts at the time of surgery. RESULTS: The median (± SD) total iron levels for endometriotic cysts and EAOC cysts were 244.4 ± 204.9 mg/L and 14.2 ± 36.6 …mg/L, respectively. EAOC patients had much lower levels of iron-related compounds compared with endometriotic cyst samples (p< 0.001). When the total iron results were analyzed using the receiver operating characteristics (ROC) curve method, the optimum diagnostic cut-off point was 64.8 mg/L, sensitivity was 90.9%, specificity was 100%, positive predictive value (PPV) was 100%, and negative predictive value (NPV) was 97.3%. Patient demographic characteristics such as tumor size, age at operation, parity and menopause were not correlated with cyst fluid iron levels. CONCLUSIONS: We conclude for the first time that iron-related compounds are important biomarkers that can predict malignant transformation with high sensitivity and specificity for women with endometriosis. Show more

Keywords: Endometriosis, malignant transformation, iron, cyst fluid

DOI: 10.3233/CBM-150484

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 493-499, 2015

Authors: Sarma, Anupam | Hazarika, Munlima | Das, Debabrata | Kumar Rai, Avdhesh | Sharma, Jagannath Dev | Bhuyan, Chidananda | Kataki, Amal Chandra

Article Type: Research Article

Abstract: BACKGROUND: Acute leukemia is a heterogenous disease having diverse phenotypes. Immunophenotyping by flowcytometry is essential for diagnosis of myeloid and lymphoid subtypes. Aberrant phenotype incidence is controversial and dissimilar results have been reported by different groups. OBJECTIVES: Purpose of the study was to determine the incidence of aberrant phenotypes in North East Indian patients with acute leukemia. METHODS: We analysed a total of 100 cases (AML = 36, ALL = 61, MPAL = 3) by multiparametric flow cytometry using an acute panel of monoclonal antibodies (MoAbs). The MoAbs were selected to identify differentiation-associated antigens …of both myeloid and lymphoid lineages. RESULTS: Aberrant phenotypes were found in 21 (58.3%) cases of AML, 36 (59.2%) cases of B-ALL and 6 (66.7%) cases of T-ALL. CD7 was the most frequent lymphoid associated antigen found in 33% of AML cases while CD117 was the myeloid antigen most frequently detected in ALL (54%) cases. Aberrant expression of CD 117 is highly significant by Fischer's exact test (P< 0.0001). CONCLUSION: We conclude that aberrant phenotypes are present in a great majority of acute leukemia patients of North East India. Future studies will be directed to correlate of these markers with prognosis and therapeutic response. Show more

Keywords: Acute leukemia, flow cytometry, aberrant phenotype, CD marker

DOI: 10.3233/CBM-150482

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 501-505, 2015

Authors: Dai, Shu-Long | Zhou, Jin | Pan, Chao | Huang, Guan | Shi, Zuo-Liang | Yang, Shi-Yong | Yang, Kun-Xing

Article Type: Research Article

Abstract: BACKGROUND: MicroRNA-145 (miR-145) plays a crucial role in cancer prognosis. OBJECTIVE: This study aimed to investigate the prognostic value of miR-145 in patients with various cancers. METHODS: We pooled published literature from PubMed, EMBASE, Web of Science and Cochrane Database of Systematic Reviews and calculated the hazard ratios (HRs) with 95% confidence intervals (CIs) to estimate the correlation between miR-145 expression levels and survival of patients with general cancers. RESULTS: A total of 615 cases from 8 studies of multiple cancers were examined in this meta-analysis. The HR for overall survival (OS) …of low miR-145 expression in multiple cancers was 1.80 (95% CI = 1.19-2.70). Furthermore, after excluding 1 study for its potential heterogeneity, the results suggested an increasing prognostic value of low miR-145 expression (HR = 2.20, 95% CI = 1.63-1.97). In addition, there was no significant difference between miR-145 expression levels and recurrence-free survival (RFS). CONCLUSION: In conclusion, our findings suggest that miR-145 expression is associated with OS in cancer patients and can serve as a promising biomarker for monitoring prognosis. Show more

Keywords: microRNA-145, cancer, prognosis, meta-analysis

DOI: 10.3233/CBM-150475

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 507-513, 2015

Authors: Mazurek, Agnieszka | Pierzyna, Magdalena | Giglok, Monika | Dworzecka, Urszula | Suwiński, Rafaƚ | Maƚusecka, Ewa

Article Type: Research Article

Abstract: BACKGROUND: Analysis of circulating cell-free DNA in blood is considered as a liquid biopsy, which enables non-invasive and repetitive investigation of the tumor DNA. The potential clinical usefulness of circulating DNA is frequently examined in lung cancer. Thus, our aim was assessment if chemotherapy influences the circulating DNA concentration. PATIENTS AND METHODS: Fifty-seven lung cancer patients in advanced stages of the disease were examined. Quantification of circulating DNA was determined by TERT amplification. RESULTS: Distant metastases and chemotherapy were significantly connected with circulating DNA level. Patients treated with conventional chemotherapy had statistically lower circulating …DNA levels when compared to patients not treated with chemotherapy. Histological types of tumor and smoking status were not associated with circulating DNA concentration. In this study, we have also genotyped the EGFR mutations in exon 19 of circulating DNA using the TaqMan PCR assays. One patient carried a deletion (2235-49del in EGFR), which has been confirmed by sequencing. CONCLUSIONS: Circulating DNA is easy to obtain, convenient biological material, although quantitative analysis cannot be used as diagnostic tool, but it can be applied to determination of EGFR mutations, basis of the tyrosine kinase inhibitors application. Show more

Keywords: Circulating DNA, cell-free DNA, lung cancer, liquid biopsy, chemotherapy

DOI: 10.3233/CBM-150471

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 515-524, 2015