microRNA and inflammatory gene expression as prognostic marker for overall survival in esophageal squamous cell carcinoma

Abstract

MicroRNAs (miRNAs) and inflammatory genes have a role in the initiation and development of esophageal squamous cell carcinoma (ESCC). In our study, we examined the potential of using miRNA and inflammatory gene expression patterns as prognostic classifiers for ESCC. Five miRNAs and 25 inflammatory-related genes were measured by quantitative reverse transcriptase PCR in tumor tissues and adjacent noncancerous tissues from 178 Chinese patients with ESCC. The expression levels of miR-21 (p = 0.027), miR-181b (p = 0.002) and miR-146b (p = 0.021) in tumor tissue and miR-21 (p = 0.003) in noncancerous tissue were associated with overall survival of patients. These data were combined to generate a miRNA risk score that was significantly associated with worse prognosis (p = 0.0001), suggesting that these miRNAs may be useful prognostic classifiers for ESCC. To construct an inflammatory gene prognostic classifier, we divided the population into training (n = 124) and test cohorts (n = 54). The expression levels of CRY61, CTGF and IL-18 in tumor tissue and VEGF in adjacent noncancerous tissue were modestly associated with prognosis in the training cohort |Z-score| > 1.5 and were subsequently used to construct a Cox regression-based inflammatory risk score (IRS). IRS was significantly associated with survival in both the training cohort (p = 0.002) and the test cohort (p = 0.005). Furthermore, Cox regression models combining both miRNA risk score and IRS performed significantly better than models with either alone (p < 0.001 likelihood ratio test). Therefore, miRNA and inflammatory gene expression patterns, alone or in combination, have potential as prognostic classifiers for ESCC and may help to guide therapeutic decisions.

CDX2 is involved in microRNA‑associated inflammatory carcinogenesis in gastric cancer

“…The miR-181 family exhibits cancer-specific expression patterns, and miR-181b is upregulated in various malignant neoplasms, including breast, pancreas, prostate, esophagus and gastric cancer (15,(26)(27)(28)(29). In gastric cancer cell lines, miR-181b significantly increased cell proliferation, migration and invasion (30).…”

Association of miR-21 with esophageal cancer prognosis: a meta-analysis

“…miR-21 is an oncogenic miRNA that has been shown to be produced at increased levels in EC, and overexpression of miR-21 plays important roles in increasing cell proliferation, migration, invasion, and survival (Li et al, 2013;Wang et al, 2013). Previous studies (Mathé et al 2009;Komatsu et al, 2013;Wang et al, 2013;Zhao et al, 2013) have suggested that miR-21 downregulation inhibits cell growth and invasion and induces cells to apoptose through targeting of the FASL, TIMP3, and RECK genes. A study by Hamano et al (2011) also indicated that miR-21 regulates stem cell function, which is involved in the resistance to chemotherapy in EC.…”

MicroRNA expression in esophageal squamous cell carcinoma: Novel diagnostic and prognostic biomarkers

“…Altered gene expression, which is the result of gene mutation or dramatic changes in gene regulation, is associated with a variety of diseases. MicroRNAs (miRNAs) act as oncogenes or tumor suppressors, mediating multiple gene expression in human cancers (10,11). Previous studies demonstrated that in ESCC, tumor-suppressive miRNAs of miR-145, miR-133a, miR-133b (12) and miR-143 (13) inhibited tumor cell proliferation and invasion.…”