MicroRNA Expression and Clinical Outcomes in Patients Treated with Adjuvant Chemotherapy after Complete Resection of Non–Small Cell Lung Carcinoma

Abstract

This study determined whether expression levels of a panel of biologically relevant microRNAs can be used as prognostic or predictive biomarkers in patients who participated in the International Adjuvant Lung Cancer Trial (IALT), the largest randomized study conducted to date of adjuvant chemotherapy in patients with radically resected non-small cell lung carcinoma (NSCLC). Expression of miR-21, miR-29b, miR-34a/b/c, miR-155, and let-7a was determined by quantitative real-time PCR in formalin-fixed paraffin-embedded tumor specimens from 639 IALT patients. The prognostic and predictive values of microRNA expression for survival were studied using a Cox model, which included every factor used in the stratified randomization, clinicopathologic prognostic factors, and other factors statistically related to microRNA expression. Investigation of the expression pattern of microRNAs in situ was performed. We also analyzed the association of TP53 mutation status and miR-34a/b/c expression, epidermal growth factor receptor and KRAS mutation status, and miR-21 and Let-7a expression. Finally, the association of p16 and miR-29b expression was assessed. Overall, no significant association was found between any of the tested microRNAs and survival, with the exception of miR-21 for which a deleterious prognostic effect of lowered expression was suggested. Otherwise, no single or combinatorial microRNA expression profile predicted response to adjuvant cisplatin-based chemotherapy. Together, our results indicate that the microRNA expression patterns examined were neither predictive nor prognostic in a large patient cohort with radically resected NSCLC, randomized to receive adjuvant cisplatin-based chemotherapy versus follow-up only. Cancer Res; 70(21); 8288-98. ©2010 AACR.

Prognostic Role of microRNA-155 in Various Carcinomas: Results from a Meta-Analysis

“…Patients were of a variety of carcinomas, including breast cancer, pancreatic ductal adenocarcinomas, esophageal cancer, hepatocellular carcinoma, leukemia, colorectal cancer, lung cancer and lymphoma. Of all the 28 studies, 16 studies (n = 2536) with HR data could be included for metaanalysis [7,[13][14][15][16][17][18][33][34][35][36][37][38][39][40][41]. Among them, seven studies (n = 1678) recruited lung cancer patients.…”

“…For example, Heegaard et al reported miR-155 could only insignificantly predict outcome with HR more than 1 but P values more than 0.05 [17]. Moreover, a study recruiting 637 lung cancer patients even suggested higher miR-155 expression may indicate better survival but the trend did not reach significance (P = 0.39) [18]. Therefore, it is necessary to conduct a systematic review and meta-analysis to summarize the findings globally and address the inconsistencies of literature.…”

MicroRNA-155 Expression has Prognostic Value in Patients with Non-small Cell Lung Cancer and Digestive System Carcinomas

“…Several studies have corroborated this finding in lung cancer and other malignant diseases including colorectal cancer, breast cancer, hepatocelluar carcinomas, pancreatic ductal adenocarcinomas and adult T-cell leukemia (Raponi et al, 2009;Greither et al, 2010;Shibuya et al, 2010;Chen et al, 2012;Han et al, 2012;Huang et al, 2012;Ishihara et al, 2012;Papaconstantinou et al, 2012); however, other reports provided insignificant or opposite evidences (Jung et al, 2009;Voortman et al, 2010;Donnem et al, 2011;Saito et al, 2011;Monsálvez et al, 2012;Shinmei et al, 2012). In order to investigate the precise association between miR-155 expression and the prognosis of patients, we combined the HRs extracted from the eligible data, and found that patients with high miR-155 expression were likely to have an unfavorable outcome.…”

MicroRNA-29b is involved in the Src-ID1 signaling pathway and is dysregulated in human lung adenocarcinoma

“…Although the sample number in our study was rather small, low miR-29b tumor levels significantly correlated with poor event-free and overall survival, whereas high miR-29b tumor levels were associated with favorable outcome. A recent study found no prognostic role for miR-29b in patients treated with adjuvant chemotherapy after complete resection of lung cancer (Voortman et al, 2010). However, patients had different histological subtypes, and the study used a different control gene for standardization and a different cut-off value.…”