Cancer Biomarkers - Volume 19, issue 2

Authors: Petrovic, Nina | Davidovic, Radoslav | Bajic, Vladan | Obradovic, Milan | Isenovic, R. Esma

Article Type: Other

Abstract: Breast cancer (BC) is a heterogeneous disease in an urgent need for developing novel research, classification, and therapy approaches. Breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) proteins are well described tumor suppressors with great potential to be the subjects of different therapies. MicroRNAs (miRNAs) are genetic elements that might be used to solve the complex BC puzzle. BRCA1 was described to be the target of up to 100 miRNAs. BRCA1 may directly repress miR-155 activity. In addition, miR-15/107/182-mediated downregulation of BRCA1 interrupt DNA repair and may change the course of BC therapy. miR-146a and miR-146-5p silencing BRCA1 …may trigger formation of triple-negative and basal-like sporadic BC cases. miR-182 might effect the therapy outcome. miR-21 targeted therapy might be useful for the treatment of BRCA2 mutation carriers. miR-342 overexpression and the absence of functional BRCA1 gene might cause synthetic lethality, which might be used as a base for future therapies. The present review discusses the latest data from studies that focus on the complex network of miRNAs and BRCA1/2 related BCs, which might be important for improving the therapy within the patients with triple-negative BC (TNBC) and basal-like BC, and for understanding the formation of TNBC. Show more

Keywords: Breast cancer, miRNA, BRCA1, BRCA2, TNBC

DOI: 10.3233/CBM-160319

Citation: Cancer Biomarkers, vol. 19, no. 2, pp. 119-128, 2017

Authors: Hanna, Glenn J. | Sridharan, Vishwajith | Margalit, Danielle N. | La Follette, Stephanie K. | Chau, Nicole G. | Rabinowits, Guilherme | Lorch, Jochen H. | Haddad, Robert I. | Tishler, Roy B. | Anderson, Karen S. | Schoenfeld, Jonathan D.

Article Type: Research Article

Abstract: BACKGROUND: HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) is increasing in incidence. Laboratory assays that identify virally-mediated disease and predict HPV clearance in OPSCC may have important prognostic implications. OBJECTIVE: Here we investigated serum, salivary HPV16 early (E) antibodies before and after definitive chemoradiotherapy (CRT) in patients with locoregionally advanced OPSCC. METHODS: We prospectively measured salivary, serum samples at the beginning of and 6-7 weeks following the completion of CRT in 44 patients. IgG antibodies targeting N- and C-terminal fragments of E2 (NE2, CE2), E6 and E7 were measured by programmable enzyme-linked immunosorbent assay. …RESULTS: We observed serum antibodies directed against HPV-associated E proteins in patients with HPV-associated OPSCC. E7 directed antibodies were detected in saliva in the majority of patients, and were associated with HPV status (p= 0.03). When analyzed longitudinally, median salivary E7 antibody levels decreased significantly post-treatment (p= 0.007). CONCLUSIONS: Our results demonstrate the feasibility of measuring HPV16 E antibodies in saliva and serum. E7 antibodies, in particular, are more detectable in saliva as compared with other E protein antibodies. Measuring E7 salivary antibody levels at various time points may have utility in understanding HPV clearance and should be explored for their ability to predict the risk of recurrence. Show more

Keywords: HPV, saliva, antibodies, oropharyngeal cancer

DOI: 10.3233/CBM-160071

Citation: Cancer Biomarkers, vol. 19, no. 2, pp. 129-136, 2017

Authors: Huang, Qing | Wang, Changjiang | Hou, Ziming | Wang, Gang | Lv, Jianghua | Wang, Hao | Yang, Jun | Zhang, Zhe | Zhang, Hongbing

Article Type: Research Article

Abstract: BACKGROUND: MicroRNA (miR)-376 family play crucial roles in cancer formation and progression. OBJECTIVE: To investigate expression patterns of circulating miR-376 members in glioma patients, and to explore their diagnostic and prognostic values. METHODS: Expression of miR-376 members in serum samples from 100 glioma patients and 50 healthy controls were detected by quantitative real-time PCR. RESULTS: Serum miR-376a, miR-376b and miR-376c in glioma patients were significantly lower than those in healthy controls (all P< 0.05). Their expression could efficiently distinguish the glioma patients from healthy controls according to the receiver operating …characteristic (ROC) analysis [for miR-376a, the area under ROC curve (AUC) = 0.872, the optimal cut-off value = 1.95, the sensitivity = 81.0% and the specificity = 82.0%; for miR-376b, AUC = 0.890, the optimal cut-off value = 2.07, the sensitivity = 82.0% and the specificity = 78.0%; for miR-376c, AUC = 0.837, the optimal cut-off value = 2.12, the sensitivity = 90.0% and the specificity = 70.0%; all P<0. 001]. Decreased expression of miR-376a, miR-376b and miR-376c in patients' sera were significantly associated with advanced WHO grade (all P< 0.01) and low KPS (all P< 0.05). Kaplan-Meier and Cox regression analyses showed that low miR-376a, miR-376b and miR-376c expression, and high grade were all independent factors predicting poor outcome of glioma patients. Notably, subgroup analyses showed that serum miR-376a, miR-376b and miR-376c levels had more significant prognostic values in patients with high grade gliomas than those with low grade gliomas. CONCLUSIONS: Aberrant expression of the miR-376 family may be involved into tumorigenesis and tumor progression of human gliomas. Circulating miR-376a, miR-376b and miR-376c may be promising non-invasive biomarkers for diagnosis and prognosis in glioma patients. Show more

Keywords: Glioma, microRNA-376 family, diagnosis, prognosis, biomarker

DOI: 10.3233/CBM-160146

Citation: Cancer Biomarkers, vol. 19, no. 2, pp. 137-144, 2017

Authors: Zhang, Yingyi | Kong, Zhe | Zhang, Yalong | Huang, Wenhua | Wu, Hai | Wan, Xuechao | Li, Yao

Article Type: Research Article

Abstract: Prostate cancer (PCa) was one of the most common cancers in males in China. Long non-coding RNAs (lncRNA), a class of non-coding RNAs with more than 200 nucleotides, played key roles in the progression of prostate cancer. GLIDR, a novel long intergenic ncRNA, was found to be upregulated in tumors compared to normal tissues by using publically databases. In the clinical validation cohort, our results showed GLIDR was significantly up-regulated in prostate cancer samples and cell lines. To explore the potential functions of the GLIDR, we constructed gene co-expression networks and applied GO analysis. Our analysis revealed that GLIDR was …involved in the regulation of translational elongation, transcription, rRNA processing, RNA splicing, signal transduction, and cell adhesion. Furthermore, a GLIDR-mediated ceRNA network in prostate cancer was also identified. We believed that this study still provided some clues in exploring new therapeutic and prognostic targets for prostate cancer. Show more

Keywords: Prostate cancer, GLIDR, prognosis, ceRNA

DOI: 10.3233/CBM-160166

Citation: Cancer Biomarkers, vol. 19, no. 2, pp. 145-150, 2017

Authors: Rismani, Elham | Fazeli, Mohammad Sadegh | Mahmoodzadeh, Habibollah | Movassagh, Aghdas | Azami, Sina | Karimipoor, Morteza | Teimoori-Toolabi, Ladan

Article Type: Research Article

Abstract: BACKGROUND: Colorectal cancer (CRC) is known as one of the most leading causes of death from cancer in the world. Wnt signaling pathway is the most important signaling pathway activated in this type of cancer. The low-density lipoprotein (LDL) receptor-related protein-6 (LRP6) functions as a co-receptor in order to trigger this signaling pathway. OBJECTIVE: The expression of LRP6 was studied in cell lines, tumoral and normal adjacent tissues from patients affected with colorectal cancer. MATERIALS AND METHODS: The expression of LRP6 was assayed by quantitative Real time PCR. RESULTS: LRP6 …is overexpressed at the transcript and protein level in HCT116 and SW480 in comparison to HUVEC as the non-cancerous cell. Furthermore, LRP6 was significantly up-regulated in 61% of human malignant tissues (p-value = 0.0008). In inherited type of disease, this upregulation was lower than other types of colorectal cancer, while in rectal cancer the overexpression was significantly higher (p-value = 0.039). Gene expression was not correlated with the age, gender and the stage of disease. CONCLUSION: Due to the profound overexpression of LRP6 in sporadic and rectal types of cancer compared to normal colonic ones, antagonist related approaches can be promising for targeted therapies of cancer. Show more

Keywords: Colorectal neoplasm, gene expression, Wnt signaling pathway, LRP6 protein, human

DOI: 10.3233/CBM-160175

Citation: Cancer Biomarkers, vol. 19, no. 2, pp. 151-159, 2017

Authors: Cai, Zerong | Xiao, Jian | He, Xiaosheng | Ke, Jia | Zou, Yifeng | Chen, Yufeng | Wu, Xianrui | Li, Xiaoling | Wang, Lei | Wang, Jianping | Lan, Ping | Wu, Xiaojian

Article Type: Research Article

Abstract: OBJECTIVE: Evaluating the prognostic significance of carcinoembryonic antigen (CEA) for colorectal cancer (CRC) patients in new cutoffs. PATIENTS: Three hundred and seventy cases and 1164 cases of CRC patients receiving tumor resection from hospitals of Sun Yat-sen University were retrospectively investigated as training cohort and validation cohort respectively. CEA was categorized into quintiles for Kaplan-Meier analysis and Cox proportional hazards regression analysis. RESULTS: CEA was categorized into quintiles with the cutoff points of (0-1.5) ng/ml, (1.5-2.3) ng/ml, (2.3-3.98) ng/ml, (3.98-8.02) ng/ml, (8.02-Maximum) ng/ml. In CRC patients from training cohort, progressively worse outcomes were …observed in each increasing quintile of CEA in term of overall survival (Log-rank Test: P< 0.0001, Log-rank Test for Trend: P< 0.0001) and progression free survival (Log-rank Test: P= 0.0002, Log-rank Test for Trend: P< 0.0001). CEA quintile was associated with overall survival (HR: 1.209, 95%CI: 1.033-1.416, P= 0.018) and progression free survival (HR: 1.195, 95%CI: 1.024-1.394, P= 0.024). Validation analysis also showed that patients with increasing CEA quintile suffered unfavorable overall survival (Log-rank Test: P= 0.0001, Log-rank Test for Trend: P= 0.0001) and progression free survival (Log-rank Test: P= 0.0001, Log-rank Test for Trend: P= 0.0001). CEA quintile was associated with overall survival (HR: 1.330, 95%CI: 1.123-1.576, P< 0.001) and progression free survival (HR: 1.218, 95%CI: 1.089-1.362, P= 0.001). CONCLUSIONS: Preoperative CEA quintile was an independent predictor of unfavorable prognosis in CRC patients. Even within normal range, CEA quintile might still impact prognosis outcomes of CRC. Show more

Keywords: Colorectal cancer, carcinoembryonic antigen, prognosis

DOI: 10.3233/CBM-160287

Citation: Cancer Biomarkers, vol. 19, no. 2, pp. 161-168, 2017

Authors: Zhang, Zijian | Cao, Yanwei | Zhao, Weiming | Guo, Lei | Liu, Wanpeng

Article Type: Research Article

Abstract: BACKGROUND: Histone deacetylase 6 (HDAC6) is correlated with poor/better survival from cancers. This study was designed to investigate the correlation between HDAC6 expression and renal cell carcinoma (RCC) patients. METHODS: A total of 45 fresh RCC samples and 132 paraffin embedded tissues as well as their corresponding adjacent non-tumor tissues were collected by surgical excision. The qRT-PCR, western blotting analysis and immunohistochemically analysis were performed to detect the expression of HDAC6. Kaplan-Meier curves analysis and Cox proportional hazards model were used to analysis patients survivals as well as to adjust stratification factors. RESULTS: …The experimental results demonstrated that HDAC6 mRNA expression level was significantly upregulated in RCC tissues compared with adjacent non-tumor tissues, and its expression was correlated with histologic grade and poor overall survival of RCC patients. RCC patients with higher HDAC6 expression showed relative poor survival. Moreover, both HDAC6 expression and histologic grade were correlated with RCC prognosis, and high HDAC6 expression was an independent, poor prognostic factor in patient with RCC. CONCLUSION: These analyses showed that high HDAC6 expression was an independent, poor prognostic factor in patients with RCC, and HDAC6 could serve as a biomarker of RCCs prognostic and an indicator for RCC progression. Show more

Keywords: Histone deacetylase 6, renal cell carcinoma, overall survival, prognosis

DOI: 10.3233/CBM-160298

Citation: Cancer Biomarkers, vol. 19, no. 2, pp. 169-175, 2017

Authors: Wang, Dong | Li, Han-Zhong | Ji, Zhi-Gang

Article Type: Research Article

Abstract: OBJECTIVE: This study aims to investigate the clinical value of laparoscopic enucleation combined with selective arterial embolization for the treatment of renal angiomyolipoma. METHODS: Data of patients who underwent laparoscopic nephron-sparing surgery for renal angiomyolipoma between July 2013 and November 2014 in our center were analyzed. RESULTS: Before surgery, 19 patients underwent selective arterial embolization, while 24 patients did not receive this treatment. Intraoperative blood loss was 46.4 ± 20.6 ml in the embolization group and 89.5 ± 30.4 ml in the non-embolization group (P= 0.000). Operation time was 90.3 ± …21.1 minutes in the embolization group and 131.7 ± 18.6 minutes in the non-embolization group (P= 0.000). Warm ischemia time was 9.5 ± 5.7 minutes in the embolization group and 24.2 ± 4.8 minutes in the non-embolization group (P= 0.001). Hospitalization time was 7.7 ± 1.1 days in the embolization group and 6.3 ± 1.3 days in the non-embolization group (P= 0.000). No serious complications occurred in patients in the embolization group, while one patient developed urinary leakage and another patient had angiomyolipoma in the operation area in the non-embolization group. Three months after the operation, serum creatinine level was 70.1 ± 13.7 μ mol/L in the embolization group and 84.2 ± 9.1 μ mol/L in the non-embolization group (P= 0.000). No tumor recurrence occurred in patients in both groups. CONCLUSION: Compared with laparoscopic partial nephrectomy alone, tumor enucleation combined with selective arterial embolization can reduce blood loss and shorten warm ischemia time. Show more

Keywords: Renal angiomyolipomas, laparascopy, enucleation, arterial embolization

DOI: 10.3233/CBM-160501

Citation: Cancer Biomarkers, vol. 19, no. 2, pp. 177-183, 2017

Authors: Yan, Hongjiang | Li, Baosheng | Fan, Tingyong | Jiang, Shumei | Wang, Renben | Sun, Mingping

Article Type: Research Article

Abstract: PURPOSE: We evaluate whether the change of heat shock protein 90a (HSP90a) level before and after definitive chemoradiotherapy (CRT) in esophageal squamous cell carcinoma (ESCC) affects tumor response and overall survival (OS). This study aimed to investigate the role of HSP90a reduction ratio after CRT. METHODS: Correlations between pre-CRT HSP90a levels and the tumor response to CRT were analysed. Patients were divided into three groups (Group 1: Serum HSP90a levels pretreatment CRT less than 124 ng/mL; Group 2: pre-CRT HSP90a of 124 ng/mL or more with HSP90a reduction ratio of 65% or more; Group 3: pre-CRT …HSP90a of 124 ng/mL or more with HSP90a reduction ratio less than 65%), and their oncologic outcomes were compared. RESULTS: The rates of good response in HSP90a low (pre-CRT HSP90a ≤ 124 ng/mL) and high groups (pre-CRT HSP90a ≤ 124 ng/mL) were 67.3% (68/101) and 37.78% (20/79), respectively (P= 0.004). The rates of good response were significantly higher in Group 1 than in Groups 2 and 3 (58.5% vs. 46.0% and 27.8%, respectively; P= 0.013). The results from statistical analysis indicated that the tumor response was significantly associated with the serum levels of pre-CRT HSP90a and HSP90a Group (P< 0.05). The OS rate was not different between Groups 1 and 2 but was significantly lower in Group 3. HSP90a Group were independent prognostic factors for OS. CONCLUSIONS: HSP90a levels could be of clinical value as a predictor of response to CRT HSP90a reduction ratio might be an independent prognostic factor for in ESCC patients treated with definitive CRT. Show more

Keywords: Esophageal squamous cell carcinoma, chemoradiotherapy, heat shock protein 90, reduction ratio

DOI: 10.3233/CBM-160502

Citation: Cancer Biomarkers, vol. 19, no. 2, pp. 185-192, 2017

Authors: Xue, Liying | Nan, Jinglong | Dong, Li | Zhang, Cuiying | Li, Hui | Na, Rentuya | He, Huijie | Wang, Yadi

Article Type: Research Article

Abstract: BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common cause of cancer-associated mortality. Uncovering novel molecular biomarkers that can predict ESCC development will improve personalized therapy. OBJECTIVE: The goal of the current study was to investigate the expression pattern of miR-483-5p and determine its prognostic value in ESCC. METHODS: We first analyzed miRNA-seq data obtained from the Cancer Genome Atlas (TCGA) cohort to evaluate the prognostic value of miR-483-5p in ESCC. Then quantitative real-time RT-PCR (qRT-PCR) was carried out to compare the miR-483-5p levels in 80 pairs of ESCC tissues …and adjacent non-cancerous tissues. The correlation between miR-483-5p levels and clinical features were determined. RESULTS: For the TCGA cohort, ESCC patients with higher miR-483-5p had significantly shorter overall survival time. The examined ESCC cancer tissues exhibited a remarkable increment in miR-483-5p expression compared with the adjacent normal tissues. miR-483-5p was positively correlated with TNM stage, lymph nodes metastasis and T stage. In addition, upregulate miR-483-5p expression was also found to be significantly associated with poor survival of ESCC patients. Furthermore, miR-483-5p expression was an independent prognostic factor for overall survival and disease free survival in ESCC patients. CONCLUSIONS: Our study demonstrates that miR-483-5p might be a tumor promoter of ESCC, which provide a promising prognostic biomarker and therapeutic target. Show more

Keywords: Biomarker, esophageal squamous cell carcinoma, miR-483-5p, prognosis

DOI: 10.3233/CBM-160506

Citation: Cancer Biomarkers, vol. 19, no. 2, pp. 193-197, 2017

Authors: Wang, Shan | Xu, Jiankai | Meng, Yan | Qiang, Dongxia | Sun, Changsheng | Shi, Lei | Zhao, Eryang

Article Type: Research Article

Abstract: PURPOSE: The objective of this study was to explore the prognostic value of in situ memory T cells and patterns of invasion (POI) in early stage oral squamous cell carcinoma (OSCC). METHODS: One hundred fifty-seven patients with early stage (cT1T2N0) OSCC were identified from a pre-existing database of patients with oral cancer and were classified by POI according to hematoxylin-eosin staining. We examined the impact of the immunohistochemical expression of CD45RO in OSCC. Overall survival (OS) curves were calculated using the Kaplan-Meier method. RESULTS: Margin status was significantly associated with local recurrence in …early stage OSCC (p= 0.000), and depth of invasion was also associated with regional recurrence (2 mm: p= 0.034; 4 mm: p= 0.015). The expression of CD45RO (p= 0.021) and POI (p= 0.027) individually was associated with OS, and patients in the group with combination score tended to have worse OS (p= 0.012). CONCLUSION: Combined evaluation of POI and CD45RO might prove to be a useful indicator for high-risk patients with occult metastases from early stage OSCC. Show more

Keywords: CD45RO, patterns of invasion, oral squmaous cell cacinoma, early stage

DOI: 10.3233/CBM-160512

Citation: Cancer Biomarkers, vol. 19, no. 2, pp. 199-205, 2017

Authors: Chen, Enjing | Zheng, Fufu | Yuan, Xiaoxu | Ye, Yunlin | Li, Xiaofei | Dai, Yuping | Chen, Lingwu

Article Type: Research Article

Abstract: AIM : This study aimed to investigate the methylation status of EGF-like and two follistatin-like domains 2 (TMEFF2 ) promoter and its correlation with tumor stage and survival outcome in renal cell carcinoma (RCC). MATERIALS AND METHODS: Paraffin-embedded specimens from 42 RCC patients were analyzed for TMEFF2 methylation by methylation-specific polymerase chain reaction. The distribution of TNM/AJCC stages and survival time were compared among patients with unmethylated and methylated TMEFF2 . RESULTS: There were 25 (59.5%) and 17 (40.5%) cases with methylated (M group) and unmethylated (M group) TMEFF2 , respectively. There were …more early-stage cancer patients in U group than in M group. Kaplan-Meier survival analysis showed that U group had a better but not significant survival outcome than M group (P = 0.123). CONCLUSION: These findings showed that TMEFF2 methylation is not rare in RCC, and methylation may play an important role in the tumorigenesis of ccRCC. Show more

Keywords: Renal cell carcinoma, promoter methylation, TMEFF2

DOI: 10.3233/CBM-161656

Citation: Cancer Biomarkers, vol. 19, no. 2, pp. 207-212, 2017

Authors: Zhong, Jia-Teng | Wang, Hai-Jun | Yu, Jian | Zhang, Jing-Hang | Wang, Shi-Feng | Yang, Xue | Su, Wei

Article Type: Research Article

Abstract: This study intended to explore the correlation of the expressions of c-Jun and Egr-1 proteins with clinicopathological features and prognosis of patients with nasopharyngeal carcinoma (NPC). From January 2008 to January 2011, 123 NPC patients and 59 patients with chronic rhinitis were enrolled in this study. Fresh NPC and normal nasopharynx tissue specimens were obtained during surgery. Immunohistochemistry (IHC) was adopted to determine the positive expressions of the c-Jun and Egr-1 proteins. A 5-year clinical follow-up was conducted on all NPC patients. The Kaplan-Meier survival curve and Cox regression model were used for survival analysis. Compared with normal nasopharynx tissues, …c-Jun expression was up-regulated but Egr-1 expression was down-regulated in NPC tissues. NPC patients with stage T3-T4 or stage III-IV had higher positive rates of c-Jun expression than those with stage T1-T2 or stage I-II. However, the positive rates of Egr-1 expression was higher in patients with stage T1-T2 or stage III-IV than those with stage T3-T4 or stage I-II. The survival rate of NPC patients with high c-Jun expression was lower than those with low/negative c-Jun expression, while the survival rate of NPC patients with high Egr-1 expression was higher than those with low/negative Egr-1 expression. The Cox regression analysis revealed that stage T3-T4, high c-Jun expression, and low Egr-1 expression were risk factors for poor prognosis of NPC patients. In conclusion, our study suggests that the c-Jun and Egr-1 proteins can serve as novel potential biomarkers for the early diagnosis and prognosis prediction of NPC. Show more

Keywords: C-Jun, Egr-1, nasopharyngeal carcinoma, clinicopathological features, prognosis

DOI: 10.3233/CBM-161710

Citation: Cancer Biomarkers, vol. 19, no. 2, pp. 213-220, 2017

Authors: Du, Zhonghai | Niu, Shuxian | Xu, Xiaoyu | Xu, Qinghui

Article Type: Research Article

Abstract: BACKGROUNDS: Hepatocellular carcinoma (HCC) is an epithelial cancer that originates from hepatocytes and it is the most common primary malignant tumor of the liver. Till now the prognosis of HCC patients is generally poor. The molecular mechanism giving rise to HCC development and recurrence is still largely unknown. MicroRNA-31 (miR-31) is among the most commonly altered microRNAs in human cancers, and alternations of miR-31 expression were reported to play pivotal roles in tumorigenesis and tumor progression. METHODS : In this work, the primary biological function of miR-31 in HCC tumorigenesis was investigated. RESULTS : …Our data showed that overexpression of miR-31 induced markedly inhibition of HCC cell proliferation, migration in vitro and inhibited xenograft tumor growth in vivo . One target gene of miR-31, NDRG3, was also demonstrated indispensable for HCC cell survival. Furthermore, miR-31 and NDRG3 were both essential for HCC cell drug resistance in adriamycin. CONCLUSIONS : We conclude that miR-31 is a crucial regulator in hepatocellular carcinoma, miR-31 and its target gene NDRG3 may be potential therapeutic targets for HCC treatment in the future. Show more

Keywords: Hepatocellular carcinoma, miR-31, NDRG3, tumorigenesis, adriamycin

DOI: 10.3233/CBM-170568

Citation: Cancer Biomarkers, vol. 19, no. 2, pp. 221-230, 2017