Association of MiR-126 with Soluble Mesothelin-Related Peptides, a Marker for Malignant Mesothelioma

Abstract

BackgroundImproved detection methods for diagnosis of malignant pleural mesothelioma (MPM) are essential for early and reliable detection as well as treatment. Since recent data point to abnormal levels of microRNAs (miRNAs) in tumors, we hypothesized that a profile of deregulated miRNAs may be a marker of MPM and that the levels of specific miRNAs may be used for monitoring its progress.Methods and ResultsmiRNAs isolated from fresh-frozen biopsies of MPM patients were tested for the expression of 88 types of miRNA involved in cancerogenesis. Most of the tested miRNAs were downregulated in the malignant tissues compared with the normal tissues. Of eight significantly downregulated, three miRNAs were assayed in cancerous tissue and adjacent non-cancerous tissue sample pairs collected from 27 formalin-fixed, paraffin-embedded MPM tissues by quantitative RT-PCR. Among the miRNAs tested, only miR-126 significantly remained downregulated in the malignant tissues. Furthermore, the performance of the selected miR-126 as biomarker was evaluated in serum samples of asbestos-exposed subjects and MPM patients and compared with controls. MiR-126 was not affected by asbestos exposure, whereas it was found strongly associated with VEGF serum levels. Levels of miR-126 in serum, and its levels in patients' serum in association with a specific marker of MPM, SMRPs, correlate with subjects at high risk to develop MPM.Conclusions and SignificanceWe propose miR-126, in association with SMRPs, as a marker for early detection of MPM. The identification of tumor biomarkers used alone or, in particular, in combination could greatly facilitate the surveillance procedure for cohorts of subjects exposed to asbestos.

Dysregulation of miRNAs and their potential as biomarkers for the diagnosis of gastric cancer

“…The expression level of miR-126 in the patient serum was found to be associated with soluble mesothelin-related peptides, which are a specific marker of malignant pleural mesothelioma (MPM). miR-126 expression was correlated with a high risk of developing MPM and may be used as a marker for the early detection of MPM (36). This study identified miR-143 and -195 as potentially useful biomarkers in human gastric cancer, due to their similar performance in the clinicopathological factor analysis.…”

Serum mesothelin and other biomarkers: what have we learned in the last decade?

“…Preliminary analysis evidence miRNAs as possible markers for diagnosis and prognosis of MPM, and hypothesize new mechanisms for the therapy of this malignancy (35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48).…”

“…Santarelli et al proposed miR-126 as useful marker because significantly remained down-regulated in the malignant tissues compared with the normal tissues (38) and in serum (41) while Kirschner et al confirmed the potential of miR-29c and miR-92a as candidate tumor markers and revealed that miR-625-3p was a promising novel diagnostic marker for MPM (39).…”

“…Several panels of biomarkers have been suggested as tools for screening and early diagnosis, clinical monitoring, prognosis and screening of MPM (60)(61)(62)(63)(64)(65)(66)(67)(68). The combinations studied are multiple: 80HdG, VEGFbeta and SMRPs (60), miR-126, in association with SMRPs (61), serum concentrations of SMRP, CA125, and CYFRA21-1 (62), combination of serum SMRP and pOPN (27), combination of SMRP and miR-103a-3p (63,64), SMRPs, miR-126 and methylated thrombomodulin promoter, Met-TM (65), fibulin-3 and SMRP (66), combination of miR-132-3 and miR-126 (48), combination of six biomarkers (SMRP-pOPN-IL6-vimentin-desmin-HGF) (56).…”

MiRNAs-based Gene Therapy on the Horizon: Novel and Effective Therapeutic Advancement

“…Although, gene expression profiling has reached a plateau in this regard, recent miRNA studies illustrate great promise whereas aberrant miRNA profiling and or abnormal miRNA levels in tissues or in plasma can perform as a robust predictor of overall survival and disease outcome in various disorders. Because numerous miRNAs are expressed in a tissue-specific manner and their levels in different organs vary in association with disease states, these small molecules represent an attractive new class of highly specific biomarkers [153][154][155][156][157]. Some reports have previously illustrated the potential of these small RNA molecules as biomarkers in cancerous patients [158].…”