Cancer Biomarkers - Volume 20, issue 4

Authors: Zhao, Chengfei | Gao, Feng | Weng, Shaohuang | Liu, Qicai

Article Type: Research Article

Abstract: Pancreatic cancers with poor prognosis are highly malignant, readily metastatic and of immune tolerance, mainly due to delayed detection. The metastatic progression and immune tolerance of pancreatic cancer is greatly attributed to the intercellular communication. However, exosomes are deemed to be the most important tool of intercellular communicators. Thus, we present a review of pancreatic cancer and exosomes in this article. We intensively summarize the progress of early pancreatic cancer and the relationship of the proliferation, progression and metastasis of pancreatic cancer and pancreatic cancer-derived exosomes, and propose new ideas of the study of pancreatic cancer.

Keywords: Pancreatic cancer, pancreatic intraepithelial neoplasia, early detection, exosomes, immune tolerance

DOI: 10.3233/CBM-170258

Citation: Cancer Biomarkers, vol. 20, no. 4, pp. 357-367, 2017

Authors: Chatterjee, Madhumita | Hurley, Laura C. | Levin, Nancy K. | Stack, Matthew | Tainsky, Michael A.

Article Type: Research Article

Abstract: BACKGROUND: Ovarian cancer is frequently diagnosed at an advanced stage and 70% of patients experience recurrence months to years from initial diagnosis. The expression of paraneoplastic antigens can result in the occurrence of onconeural autoantibodies in ovarian cancer that may be associated with neurological disorders that are clinically manifested in patients before diagnosis of ovarian cancer. These paraneoplastic antigens can serve as excellent biomarkers not only for early detection but also for monitoring ovarian cancer recurrence. OBJECTIVE: To assess the immunoreactivity of our previous 3 biomarkers along with 3 paraneoplastic antigens, HARS, Ro52 and CDR2 for …the evaluation of their sensitivity in predicting recurrence before the clinical relapse of the ovarian cancer. METHODS: Western blot immunoassays were performed to assess the immunoreactivity of 6 antigens with 21 recurrent ovarian cancer patients. RESULTS: The results indicated that antibodies to HARS, Ro52, CDR2 and 5H6 antigens predicted ovarian cancer recurrence 5.03 months before the clinical or symptomatic relapse in 21 ovarian cancer patients with a sensitivity of 90.5% when CA125 levels were below the standard cutoff (35 U/ml). CONCLUSION: Our study suggests that appearance of onconeural antibodies prior to the rise in CA125 during post treatment surveillance can be a useful diagnostic to predict ovarian cancer recurrence. Show more

Keywords: Paraneoplastic syndromes, paraneoplastic antigens, humoral immune response, onconeural autoantibodies, serological screening, immunoreactivity

DOI: 10.3233/CBM-170652

Citation: Cancer Biomarkers, vol. 20, no. 4, pp. 369-387, 2017

Authors: Celik, Zeliha Esin | Kaynar, Mehmet | Karabagli, Pinar | Gergerlioglu, Nursadan | Goktas, Serdar

Article Type: Research Article

Abstract: BACKGROUND: Ring Box Protein-1 (RBX-1), a component of SCF E3 ubiquitin ligases, has a crucial role in bladder urothelial cell carcinoma (UCC) carcinogenesis and progression. OBJECTIVES: In the present study, it is aimed to determine the expression of RBX-1 protein in bladder UCC and the association between tumor grade, stage and RBX-1 expression. METHODS: Ninety UCC samples and 20 samples containing foci of normal bladder urothelium were recruited and analyzed immunohistochemically in terms of RBX-1 expression. Immuno-reactivity scoring system (IRS) was used to determine RBX-1 expression levels. RESULTS: RBX-1 overexpression …was associated with high tumor grade (p = 0.001) and advanced stage (p = 0.001). pT1 tumors showed higher RBX-1 expression than pTa tumors. pT2 tumors showed not only higher expression than pTa tumors but also higher expression than the total of pTa and pT1 groups combined. There was no statistically significant relation between RBX-1 expression and patient gender (p = 0.116) or age (p = 0.191). CONCLUSIONS: In bladder UCC, RBX-1 overexpression is associated with high tumor grade and advanced stage and represents biological potential of invasiveness and aggressive disease. Results of the present study have to be supported with further studies to reveal clinical and therapeutic implications of RBX-1 overexpression in bladder UCC. Show more

Keywords: Urothelial cell carcinoma, prognosis, invasiveness, Ring Box-1, immunohistochemistry

DOI: 10.3233/CBM-170002

Citation: Cancer Biomarkers, vol. 20, no. 4, pp. 389-394, 2017

Authors: Allaoui, Roni | Hagerling, Catharina | Desmond, Eva | Warfvinge, Carl-Fredrik | Jirström, Karin | Leandersson, Karin

Article Type: Research Article

Abstract: BACKGROUND: Tumor-infiltrating lymphocytes (TILs) have a strong prognostic value in various forms of cancers. These data often refer to use of the pan-T cell marker CD3, or the cytotoxic T lymphocyte marker CD8α . However, T cells are a heterogeneous group of cells with a wide array of effector mechanisms ranging from immunosuppression to cytotoxicity. OBJECTIVE: In this study we have investigated the prognostic effects of some unconventional T cell subtypes in breast cancer; γ ⁢ δ T cells, IL-17 + T cells and FoxP3 + …T cells (T regs ) in relation to the conventional CD3 and CD8α T cell markers. METHODS: This was done using immunohistochemistry on a human breast cancer tissue microarray consisting of 498 consecutive cases of primary breast cancer. RESULTS: Infiltration of γ ⁢ δ T cells and T cell infiltration in general (CD3), correlated with a good prognosis, while T reg infiltration with a worse. Infiltration of γ ⁢ δ T cells was associated with a significantly improved clinical outcome in all breast cancer subtypes except triple negative tumors. Only infiltration of either CD3 + or CD8α + cells was independently associated with better prognosis for all breast cancer patients. CONCLUSIONS: This study sheds further light on the prognostic impact of various T cell subtypes in breast cancer. Show more

Keywords: Breast cancer, T lymphocytes, TILs, prognosis, unconventional T cells

DOI: 10.3233/CBM-170026

Citation: Cancer Biomarkers, vol. 20, no. 4, pp. 395-409, 2017

Authors: Deng, Wen | Meng, Zimin | Sun, Aitao | Yang, Zhihong

Article Type: Research Article

Abstract: BACKGROUND: The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing worldwide. Pioglitazone is a pharmacologic agonist of peroxisome proliferators-activated receptor-γ (PPAR-γ ) that was reported to ameliorate hepatic steatosis and inflammatory changes. OBJECTIVE: We aimed to evaluate the effects of pioglitazone in NAFLD and investigate the underlying mechanism by testing platelet derived growth factor (PDGF) and tissue inhibitory of metalloproteinase-2 (TIMP-2). METHODS: A total of C57BL/6 wild-type mice were randomized to three groups, control group (NC, n = 60), high-fat control …group (HF, n = 60), and pioglitazone treatment group (L , n = 60). Mice were administrated with high-fat diet to construct NAFLD model. Enzyme-linked immunosorbent assay (ELISA) was used to measure protein expression of PDGF and TIMP-2. Liver histology samples were stained with hematoxylin and eosin (H&E). RESULTS: Upon pioglitazone treatment, the PDGF and TIMP-2 expression levels were decreased compared with high-fat diet-fed mice devoid of drug stimulation. Analysis of liver histology showed pioglitazone treatment could reduce steatosis and inflammatory changes, which was helpful to inhibit hepatic fibrosis in NAFLD mice. CONCLUSIONS: The study showed pioglitazone might exert an inhibitory effect on hepatic inflammation and fibrosis in NAFLD. Moreover, this study provided novel evidence for the promising clinical application of pioglitazone in intervening NAFLD. Show more

Keywords: NAFLD, pioglitazone, hepatic fibrosis, PDGF, TIMP-2

DOI: 10.3233/CBM-170157

Citation: Cancer Biomarkers, vol. 20, no. 4, pp. 411-415, 2017

Authors: Gong, Wanjun | Tian, Ming | Qiu, Honggen | Yang, Zhenhua

Article Type: Research Article

Abstract: To evaluate the diagnostic efficacy and prognostic value of serum long non-coding RNA (lncRNA) HIF 1alpha-antisense RNA 1 (HIF1A-AS1) in patients with colorectal carcinoma (CRC). We obtained serum samples from 151 CRC patients and 160 health controls. Serum level of HIF1A-AS1 was detected via real-time PCR (RT-PCR). Receiver operating characteristics (ROC) curve analysis was conducted to determine the diagnostic value of HIF1A-AS1. Then HIF1A-AS1 in CRC was divided into high- and low-expression groups, and the associations of the HIF1A-AS1 serum level with clinicopathological features and prognosis were analyzed. Serum level of HIF1A-AS1 was significantly increased from CRC patients as compared …to those of health controls (P < 0.05). ROC curve analysis revealed a relative high diagnostic performance of HIF1A-AS1 to distinguish CRC from health controls, with the area under the curves (AUC) of 0.960 (95% CI: 0.940 ∼ 0.980; P < 0.001). Kaplan-Meier analysis showed that differentiation degree, tumor size, TNM stage, T stage, N stage, M stage and serum level of HIF1A-AS1 were all linked to CRC prognosis (All P < 0.05). Compared to CRC patients with low HIF1A-AS1 expression, high expression of patients were associated with a shorter 5-year-survival rate (P < 0.001). Multivariate Cox regression analysis revealed that lower differentiation degree, tumor > 5 cm and higher expression of HIF1A-AS1 were independent risk factors affecting the survival rate of patients with CRC (P < 0.05). Our results illustrated that elevated serum HIF1AAS1 could be clinically functioned as a potential biomarker for CRC diagnoses and prognosis. Show more

Keywords: Long chain noncoding RNA, HIF1A-AS, colorectal carcinoma, diagnosis, prognosis, clinicopathological features

DOI: 10.3233/CBM-170179

Citation: Cancer Biomarkers, vol. 20, no. 4, pp. 417-424, 2017

Authors: Wang, Jintao | Ma, Weimin | Liu, Yidong

Article Type: Research Article

Abstract: This article has been retracted, and the online PDF has been watermarked ``RETRACTION''. The retraction notice is available at http://doi.org/10.3233/CBM229006.

Keywords: Bladder cancer, lncRNA HULC, cell proliferation, cell apoptosis, ZIC2, PI3K/AKT

DOI: 10.3233/CBM-170188

Citation: Cancer Biomarkers, vol. 20, no. 4, pp. 425-434, 2017

Authors: Quillien, Véronique | Lavenu, Audrey | Ducray, François | Meyronet, David | Chinot, Olivier | Fina, Frédéric | Sanson, Marc | Carpentier, Catherine | Karayan-Tapon, Lucie | Rivet, Pierre | Entz-Werle, Natacha | Legrain, Michèle | Zalcman, Emmanuèle Lechapt | Levallet, Guenaelle | Escande, Fabienne | Ramirez, Carole | Chiforeanu, Dan | Vauleon, Elodie | Figarella-Branger, Dominique

Article Type: Research Article

Abstract: BACKGROUND: Pyrosequencing is recognized as a strong technique to analyze the MGMT status of glioblastoma patients. The most commonly used assay, quantifies the methylation levels of CpGs 74 to 78. A more recent CE-marked In Vitro Diagnostic Medical Device (CE-IVD) assay, Therascreen, analyzes CpGs 76–79. METHODS: We performed a comparison of these two assays to evaluate the potential impact of this shift in analyzed CpGs. Therascreen analysis was centrally performed for 102 glioblastoma patients, who were part of a prospective multicenter trial. RESULTS: A strong correlation was observed for the mean values of …the 4 or 5 analyzed CpGs, with lower values recorded using the Therascreen assay, especially for values greater than 20%. When considering a classification in 3 categories (> 12%: methylated; ⩽ 8%: unmethylated; 9–12%: grey zone), 93% of patients were identically classified between the two assays. Using a binary classification, 95% and 97% of patients were identically classified with cut-offs of 8% and 12%, respectively. A strong prognostic significance was observed for both assays: median overall survival were 15.9 months and 34.9 months for respectively unmethylated and methylated patients with either test. CONCLUSION: The results demonstrate that these assays may be used interchangeably. Show more

Keywords: Glioblastoma, MGMT methylation, pyrosequencing, CE-IVD kit

DOI: 10.3233/CBM-170191

Citation: Cancer Biomarkers, vol. 20, no. 4, pp. 435-441, 2017

Authors: Yuan, G.Q. | Wei, N.L. | Mu, L.Y. | Wang, X.Q. | Zhang, Y.N. | Zhou, W.N. | Pan, Y.W.

Article Type: Research Article

Abstract: BACKGROUND: Although O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation status is an important marker for glioblastoma multiforme (GBM), there is considerable variability in the clinical outcome of patients with similar methylation profles. OBJECTIVE: We examined whether a MicroRNA (miRNA) signature can be identified for predicting clinical outcomes and helping in treatment decisions. METHODS: The differentially expressed miRNAs were evaluated in 6 pairs of short- (⩽ 450 days) and long-term survivors (>  450 days) by using microarray. Real time quantitative PCR (qRT-PCR) was applied to further verify screened miRNAs with …a greater number of samples (n = 48). Meanwhile, functional interpretation of miRNA profile was carried out based on miRNA-target databases. In addition, MGMT promoter methylation status was tested by means of pyrosequencing (PSQ) testing. RESULTS: Six miRNAs were upregulated in the long-term survival group (fold change ⩾ 2.0, P < 0.05). The further verification by qRT-PCR indicated that the increase in let-7g-5p, miR-139-5p, miR-17-5p and miR-9-3p level in long-term survivors was statistically significant. Kaplan-Meier survival analysis showed that high expression of a prognostic 4-miRNA signature was significantly associated with good patient survival (p = 0.0012). The signature regulated signaling pathways including Calcium, MAPK, ErbB, mTOR and cell cycle involved in carcinogenesis from glial progenitor cell to primary GBM. CONCLUSIONS: The 4-miRNA signature was identified as an independent prognostic biomarker that identified patients who have a favorable outcome. Show more

Keywords: Glioblastoma, promoter methylation, MicroRNAs (miRNAs), O-6-methylguanine-DNA methyltransferase (MGMT), epigenetic silencing

DOI: 10.3233/CBM-170205

Citation: Cancer Biomarkers, vol. 20, no. 4, pp. 443-452, 2017

Authors: Lai, Xianliang | Deng, Zhifeng | Guo, Hua | Zhu, Xingen | Tu, Wei

Article Type: Research Article

Abstract: This article has been retracted, and the online PDF replaced with this retraction notice.

DOI: 10.3233/CBM-170249

Citation: Cancer Biomarkers, vol. 20, no. 4, pp. 453-, 2017