title: 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.
authors.affiliation: Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Schetter
authors.forename: Geoffrey B
authors.initials: GB
authors.lastname: Yang
authors.forename: Giang
authors.initials: G
authors.lastname: Nguyen
authors.forename: Ewy A
authors.initials: EA
authors.lastname: Mathé
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Cai
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.forename: Fangfang
authors.initials: F
authors.lastname: Liu
authors.forename: Dong
authors.initials: D
authors.lastname: Hang
authors.forename: Haijun
authors.initials: H
authors.lastname: Yang
authors.forename: Xin Wei
authors.initials: XW
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Ke
authors.forename: Curtis C
authors.initials: CC
authors.lastname: Harris
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis
chemical_list: D035683:MicroRNAs