Identification of two novel biomarkers of rectal carcinoma progression and prognosis via co-expression network analysis.

mRNA expression profiles provide important insights on a diversity of biological processes involved in rectal carcinoma (RC). Our aim was to comprehensively map complex interactions between the mRNA expression patterns and the clinical traits of RC. We employed the integrated analysis of five microarray datasets and The Cancer Genome Atlas rectal adenocarcinoma database to identify 2118 consensual differentially expressed genes (DEGs) in RC and adjacent normal tissue samples, and then applied weighted gene co-expression network analysis to parse DEGs and eight clinical traits in 66 eligible RC samples. A total of 16 co-expressed gene modules were identified. The green-yellow and salmon modules were most appropriate to the pathological stage (R = 0.36) and the overall survival (HR =13.534, P = 0.014), respectively. A diagnostic model of the five pathological stage hub genes (SCG3, SYP, CDK5R2, AP3B2, and RUNDC3A) provided a powerful classification accuracy between localized RC and non-localized RC. We also found increased Secretogranin III (SCG3) expression with higher pathological stage and poorer prognosis in the test and validation set. The increased Homer scaffolding protein 2 (HOMER2) expression with the favorable survival prediction efficiency significantly correlated with the markedly reduced overall survival of RC patients and the higher pathological stage during the test and validation set. Our findings indicate that the SCG3 and HOMER2 mRNA levels should be further evaluated as predictors of pathological stage and survival in patients with RC.

Clinicopathological and prognostic significance of circulating tumor cells in patients with head and neck cancer: a meta-analysis.

BACKGROUND: Many studies have assessed the clinical use of circulating tumor cells (CTCs) in head and neck cancer, but the clinicopathological and prognostic significance of CTCs is still unclear. MATERIALS AND METHODS: Two authors systematically searched the studies independently with keywords in PubMed, MEDLINE, EMBASE, Science Citation Index Expanded and Cochrane Library (from inception to February 2017). The estimated hazard ratio (HR), risk ratio (RR) and their 95% confidence intervals (95% CIs) were set as effect measures. All analyses were performed by STATA 12.0. RESULTS: A total of 17 studies were included in this meta-analysis. Positive CTCs were significantly associated with poor overall survival (HR =2.80, 95% CI: 1.34-5.86), disease-free survival (HR =3.86, 95% CI: 2.03-7.36) and progression-free survival (HR =3.31, 95% CI: 1.71-6.42). CTC-positive patients tend to have higher recurrence (RR =2.13, 95% CI: 1.26-3.59) and regional lymph node metastasis (RR =1.18, 95% CI: 1.02-1.36) rate and a more advanced tumor stage (RR =1.16, 95% CI: 1.03-1.32). CONCLUSION: Our meta-analysis has confirmed the significant prognostic value of CTCs in head and neck cancer patients. The presence of CTCs could be used as a monitoring tool for tumor status of head and neck cancer, especially for the early detection of the tumor recurrence and progression, advanced disease and the node metastasis.

Expression of cyclooxygenase-2 in colorectal cancer and its clinical significance.

AIM: To clarify the clinicopathologic significance of COX-2 expression in human colorectal cancer. METHODS: A total of 128 surgically resected colorectal cancer specimens were immunohistochemically analyzed with the use of anti-COX-2, anti-VEGF and anti-MMP-2 antibodies. The relationship between the cyclooxygenase-2 expression in primary lesions of colorectal cancer and clinicopathologic parameters was evaluated by chi-square test. RESULTS: Among 128 cases of colorectal cancer, 87 (67.9%) were positive for cyclooxygenase-2. The expression of cyclooxygenase-2 was significantly correlated with the depth of invasion, stage of disease, and metastasis (lymph node and liver). Patients in T3-T4, stages III-IV and with metastasis had much higher expression of cyclooxygenase-2 than ones in T1-T2, stages I-II and without metastasis (P<0.05). Among 45 cases of colorectal cancer with lymph node metastasis, the COX-2- positive rate was 86.7% (39/45) for primary lesions and diffuse cytoplasmic staining for COX-2 protein was detected in cancer cells in 100% of metastatic lesions of the lymph nodes. VEGF expression was detected in 49 tumors (38.3%), and VEGF expression was closely correlated with COX-2 expression. The positive expression rate of VEGF (81.6%) in the cyclooxygenase-2-positive group was higher than that in the cyclooxygenase-2- negative group (18.4%, P<0.05). MMP-2 expression was detected in 88 tumors (68.8%), and MMP-2 expression was closely correlated with COX-2 expression. The positive expression rate of MMP-2 (79.6%) in the positive COX-2 group was higher than that in the negative COX-2 group (20.4%, P<0.05). CONCLUSION: Cyclooxygenase-2 may be associated with tumor progression by modulating the angiogenesis and cancer cell motility and invasive potential in colorectal cancer and it can be used as a possible biomarker.

Cyclooxygenase-2 expression and angiogenesis in colorectal cancer.

AIM: Cyclooxygenase-2 is involved in a variety of important cellular functions, including cell growth and differentiation, cancer cell motility and invasion, angiogenesis and immune function. However, the role of cyclooxygenase-2 as an angiogenic factor in colorectal cancer tissue is still unclear. We investigated the relationship between cyclooxygenase-2 and angiogenesis by analyzing the expression of cyclooxygenase-2 in colorectal cancer tissue, as well as its association with vascular endothelial growth factor (VEGF) and microvascular density (MVD). METHODS: The expression of cyclooxygenase-2, VEGF, as well as MVD was detected in 128 cases of colorectal cancer by immunohistochemical staining. The relationship between the cyclooxygenase-2 and VEGF expression and MVD was evaluated. Our objective was to determine the effect of cyclooxygenase-2 on the angiogenesis of colorectal cancer tissue. RESULTS: Among 128 cases of colorectal cancer, 87 were positive for cyclooxygenase-2 (67.9 %), and 49 for VEGF (38.3 %), respectively. The microvessel counts ranged from 23 to 142, with a mean of 51.7 (standard deviation, 19.8). The expression of cyclooxygenase-2 was correlated significantly with the depth of invasion, stage of disease, metastasis (lymph node and liver), VEGF expression and MVD. Patients in T3-T4, stage III-IV and with metastasis had much higher expression of cyclooxygenase-2 than patients in T1-T2, stage I-II and without metastasis (P<0.05). The positive expression rate of VEGF (81.6 %) in the cyclooxygenase-2 positive group was higher than that in the cyclooxygenase-2 negative group (18.4 %, P<0.05). Also, the microvessel count (56+/-16) in cyclooxygenase-2 positive group was significantly higher than that in cyclooxygenase-2 negative group (43+/-12, P<0.05). The microvessel count in tumors with positive cyclooxygenase-2 and VEGF was the highest (60+/-18, 41-142, P<0.05), whereas that in tumors with negative cyclooxygenase-2 and VEGF was the lowest (39+/-16, 23-68, P<0.05). CONCLUSION: Cyclooxygenase-2 may be associated with tumor progression by madulating the angiogenesis in colorectal cancer tissue and used as a possible biomarker.