miRNA profiling in serum and tissue samples to assess noninvasive biomarkers for NSCLC clinical outcome

Abstract

In NSCLC, the altered expression of some miRNAs in primary tumor tissues has been correlated with diagnosis and prognosis, while the role of circulating miRNAs as cancer biomarkers is currently emerging. MiRNA expression profile through miRNA Affymetrix array was evaluated on a training set formed by the tumor component (n = 30 NSCLC serum, n = 11/30 tumor tissues) and the control component (n = 10 healthy serum and n = 11/30 noncancerous counterparts). Statistical analyses highlighted the following: a = 55 miRNAs deregulated in tumor serum, b = 27 miRNAs deregulated in tumor tissues, and c = 2 miRNAs deregulated both in tumor serum and in tumor tissues. MiRwalk tool and enrichment pathway analyses selected some miRNAs whose target genes are correlated with the main pathways involved in NSCLC tumorigenesis. The altered expression of the selected miR-486-5p (a), miR-29c* (b), and miR-133a (c) was confirmed in the validation set (n = 40). MiR-486-5p had a higher expression in tumor serum than in tumor tissues (P = 0.004), and miR-29c* showed a lower expression in tumor tissues than in tumor serum (P < 0.001). MiR-133a had a not different expression in both tumor serum and tumor tissues (P = 0.07). The low level of miR-486-5p expression in the serum of affected patients was associated with a worse time to progression of disease (P = 0.010), and serum level of miR-486-5p was a significant prognostic indicator of NSCLC (adjusted hazard ratio = 0.179, P = 0.019). These data suggest the possibility to monitor affected patients through serum and/or tissue samples, analyzing the altered expression of specific miRNAs, in order to detect prognostic biomarkers in the NSCLC.

Prognostic Value of microRNA-133a Expression and Its Clinicopathologic Significance in Non-Small Cell Lung Cancer: A Comprehensive Study Based on Meta-Analysis and the TCGA Database

“…All datasets with references and reasons for excluding publications are summarized in Supplemental Table 1 (www.karger.com/?DOI=492343). Among the 5 included studies [22,23,24,25,26], 4 reported the OS [22,23,24,25] and 2 involved clinicopathologic parameters [23,26]. The characteristics and quality scores of the included studies are summarized in Supplemental Tables 2 and 3 (www.karger.com/?DOI=492343).…”

“…As shown in Supplemental Table 2 (www.karger.com/?DOI=492343) , 4 studies provided sufficient OS data for this meta-analysis and 2 studies achieved statistical significance correlating high expression of miR-133a with better survival outcome in NSCLC patients [22,23]; the remaining 2 studies reported no statistical significance in relation to miR-133a expression and survival time [24,25]. The combined HR based on the included studies was 0.561 (95% CI 0.396-0.794, p = 0.001, I 2 = 0%) (fig.…”

“…In the previous meta-analysis [31], no statistical significance was detected for the prognostic value of miR-133a expression in NSCLC, likely due to the limited scale with only 169 patients involved in the 2 included studies [22,25]. Our main aim in the current meta-analysis including 5 original studies with 364 patients [22,23,24,25,26]was to investigate the correlation between miR-133a expression and survival time in NSCLC. We found that miR-133a might serve as a prognostic biomarker, and high expression of miR-133a was also correlated with a better OS outcome for NSCLC patients.…”

“…However, this provides merely a few tumor cells of poor quality. Considering tumor heterogeneity and genetic alterations during the processes of invasion, progression, metastasis, or chemotherapy treatment, the problem of deficient tumor samples might also exist in molecular analysis [24]. Therefore, a noninvasive, cheap, and easy approach to acquiring samples which could give reliable information on the growth and biology of NSCLC is urgently needed.…”

“…However, other studies reported that lower expression of miR-133a correlates with favorable outcome for cancer patients [17,21]. Likewise, the function of miR-133a in NSCLC is also inconsistent, with increased expression of miR-133a having been linked to favorable survival outcome and prognosis in some studies [22,23] but not others [24,25]. Meanwhile, the correlation of miR-133a with clinicopathologic parameters such as distant metastasis, lymph node metastasis, T stage, and clinical stage is also controversial in NSCLC [23,26].…”