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