Cancer Biomarkers

Functional polymorphisms in matrix metalloproteinases can increase or decrease the risk of cancer. This study focused on ovarian cancer and investigated how polymorphisms in the coding region of MMP-14 and the promoter region of MMP-2 are related to clinical characteristics including survival.

In 144 patients with ovarian tumours from a Caucasian population, polymorphisms of MMP-14 ( + 7096 and + 6767) and MMP-2 ( - 735 and - 1306) were analysed. These results were then correlated to the immunohistochemical expression of MMP-14 and MMP-2 and clinical characteristics.

In these patients, the MMP-14 + 7096 polymorphism showed only TT genotype, in sharp contrast to the described MAF (minimal allele frequency) C of 27%. The MMP-14 + 6767 G > A polymorphism was found to have a hazard ratio of 2.09 (CI 1.00–4.35, p 0.046) for recurrence-free survival in advanced-stage patients. However, this significance disappeared after Bonferroni correction for multiple testing. No other correlations between MMP-14 and MMP-2 polymorphisms, immunohistochemistry and clinical characteristics were found, except between the MMP-2 - 1306 polymorphism and differentiation grade, with a Spearman correlation coefficient of - 0.19, p 0.064.

In ovarian cancer, the MMP-14 + 6767 G > A polymorphism in the coding region seems to improve recurrence-free survival with a hazard ratio of 2.09 (CI 1.00–4.35, p 0.046). However, as this significance disappeared after correction for multiple testing, there is a need for further research on the functional effect of this change in the MMP-14 gene with larger patient sample sizes.

: The aim of this study was to evaluate the prognostic value of a novel tumor marker index (TMI) based on preoperative serum levels of squamous cell carcinoma antigen (SCC) and cytokeratin 19 fragment (CYFRA 21-1) for patients with resectable esophageal squamous cell carcinoma (ESCC).

A total of 315 ESCC patients who had underwent curative surgery between 2008 and 2012 were retrospectively included in this study. The TMI was defined as the geometric mean of normalized SCC and CYFRA21-1 levels. Univariate and multivariate survival analyses were performed to confirm the clinical and prognostic significance of preoperative SCC and CYFRA 21-1 levels and TMI.

Elevated preoperative SCC was associated with histological grade, pT status, lymph node status and TNM stage. Elevated preoperative CYFRA 21-1 was correlated with tumor size, lymph node status and TNM stage. The overall survival of patients with elevated SCC and CYFRA 21-1 levels was significantly poorer than that of patients with normal levels. Multivariate survival analysis identified that preoperative SCC ( P = 0.353) and CYFRA 21-1 ( P = 0.139) were not independent prognostic factors. The cut-off value of TMI based on SCC and CYFRA 21-1 was 0.531, and the patients were subdivided into high and low TMI groups. The 5-year survival rate of patients with high TMI was 30.9%, which was significantly lower than that of patients with low TMI (50.4%, P < 0.05). Multivariate analysis identified the TMI (HR 1.371; 95% CI 1.024-1.836; P = 0.034) as an independent prognostic factor.

Elevated preoperative SCC and CYFRA 21-1 levels were associated with aggressive cancer behavior in ESCC. The TMI based on preoperative SCC and CYFRA 21-1 might serve as a novel marker that can be used to predict the prognosis of ESCC patients.

There were no specific indicators for the early detection of pancreatic cancer.

To analyze the diagnostic and prognostic value of CA19-9 plus B7-H4 detection in preoperative serum or surgical tissues of patients with pancreatic cancer.

One hundred and eighty-eight patients with pancreatic cancer and 25 controls were recruited. Their preoperative serum CA19-9 level was detected chemiluminescently, and B7-H4 expression in pancreatic cancer tissues was assessed immunohistochemically. The diagnostic and prognostic utility of detecting CA19-9, B7-H4 and their combination was evaluated.

CA19-9 and B7-H4 levels were significantly upregulated in patients with pancreatic cancer compared with those in controls. The diagnostic value of combined CA19-9 plus B7-H4 detection was markedly better than that achieved from their separate detection analyzed with receiver operating characteristic curve. Sensitivity and specificity of the combined detection in the pancreatic cancer group was significantly increased compared with single detection. B7-H4 detection showed better prognostic value than detection of CA19-9. However, CA19-9 had high sensitivity and low specificity, while B7-H4 showed the opposite. The sensitivity of the combined prognosis was not significantly different to B7-H4 alone.

The combined detection of CA19-9 and B7-H4 could become a new method for the clinical diagnosis and prognosis of pancreatic cancer.

The expression of neuropilin-1 (NRP-1) in Epstein-Barr virus (EBV)-associated lymphomas and its relationships with clinicopathological parameters was investigated.

The researchers compared 111 cases of patients with lymphoma to 20 cases of reactive lymphoid hyperplasia. In situ hybridization was applied to observe the expression of EBV-encoded RNA (EBER) in lymphomas, and immunohistochemistry was used to detect the NRP-1 expression in lymphoma tissues and lymph node tissues with reactive hyperplasia.

In these 111 cases, the EBER of 62 cases (55.9%) appeared positive. NRP-1 was relatively highly expressed in lymphomas ( P = 0.019). Further, NRP-1 showed higher expression in lymphomas with positive EBER than in negative ones. A comprehensive analysis revealed that NRP-1 was differently expressed in NK/T-cell lymphoma, Hodgkin’s lymphoma, diffuse large B-cell lymphoma, and anaplastic large cell lymphoma ( P = 0.027). Moreover, highly expressed NRP-1 was found to be a useful independent prognostic factor in assessing overall survival and progression-free survival rates in cases of non-Hodgkin’s lymphoma (NHL).

NRP-1 exhibited higher expression in lymphomas, and it was positively expressed in EBV-positive lymphomas. Moreover, highly expressed NRP-1 can be used as an undesirable independent prognostic factor in NHL.

Guanylate binding protein-1 (GBP1) is highly associated with cell proliferation, and can modulate growth and invasiveness of gliomas. The relationship between GBP1 expression and the prognosis of glioma patients is further evaluated for the purpose of investigating whether GBP1 can serve as an predictor for evaluating prognosis of glioma patients.

GBP1 expression in 528 glioblastoma multiforme (GBM) patients of The Cancer Genome Atlas (TCGA) database were investigated, then 103 surgical specimens from glioma patients in our center were further evaluated. The effect of GBP1 on proliferation, invasion and migration of glioma cells in vitro was analyzed, and the effects of GBP1 on sensitivity of radiotherapy and chemotherapy on glioma cells in vitro were also analyzed. GBP1 associated signaling pathways were identified with Gene Set Enrichment Analysis (GSEA). Besides, the effect of GBP1 expression on proliferation of glioma cells in vivo was analyzed.

In both TCGA database and our clinical data, GBM tissues exhibited increased mRNA expression of GBP1 gene, its expression level was co-related to PETN deletion and EGFR amplification, and was associated with prognosis of GBM patients. GBP1 overexpression can enhance migration and invasion ability of tumor cells in vitro, and in vivo studies showed that GBP1 can promote tumor proliferation, decrease survival in tumor-bearing mice. GSEA analysis predicted that GBP1 may play its biological roles via toll-like receptor pathway.

This study provides new insights and evidences that high level expression of GBP1 is significantly correlated with progression and prognosis in GBMs. Furthermore, transfection of GBP1 revealed its regulation on migration and invasiveness of glioma cells, decreasing sensitivity of chemotherapeutic agent, shortening survival of tumor-bearing animals. These data demonstrate that GBP1 may serve as a novel prognostic biomarker and a potential therapeutic target for gliomas.