Dataset Information

A Prognostic Role for Circulating microRNAs Involved in Macrophage Polarization in Advanced Non-Small Cell Lung Cancer.

ABSTRACT: Circulating microRNAs (miRNAs) are key regulators of the crosstalk between tumor cells and immune response. In the present study, miRNAs (let-7c, miR-26a, miR-30d, miR-98, miR-195, miR-202) reported to be involved in the polarization of macrophages were examined for associations with the outcomes of non-small cell lung cancer (NSCLC) patients (N = 125) treated with first-line platinum-based chemotherapy. RT-qPCR was used to analyze miRNA expression levels in the plasma of patients prior to treatment. In our results, disease progression was correlated with high miR-202 expression (HR: 2.335; p = 0.040). Additionally, high miR-202 expression was characterized as an independent prognostic factor for shorter progression-free survival (PFS, HR: 1.564; p = 0.021) and overall survival (OS, HR: 1.558; p = 0.024). Moreover, high miR-202 independently predicted shorter OS (HR: 1.989; p = 0.008) in the non-squamous (non-SqCC) subgroup, and high miR-26a was correlated with shorter OS in the squamous (SqCC) subgroup (10.07 vs. 13.53 months, p = 0.033). The results of the present study propose that the expression levels of circulating miRNAs involved in macrophage polarization are correlated with survival measures in NSCLC patients, and their role as potential biomarkers merits further investigation.

SUBMITTER: Monastirioti A

PROVIDER: S-EPMC8391493 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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A Prognostic Role for Circulating microRNAs Involved in Macrophage Polarization in Advanced Non-Small Cell Lung Cancer.

Monastirioti Alexia A Papadaki Chara C Rounis Konstantinos K Kalapanida Despoina D Mavroudis Dimitrios D Agelaki Sofia S

Cells 20210805 8

Circulating microRNAs (miRNAs) are key regulators of the crosstalk between tumor cells and immune response. In the present study, miRNAs (let-7c, miR-26a, miR-30d, miR-98, miR-195, miR-202) reported to be involved in the polarization of macrophages were examined for associations with the outcomes of non-small cell lung cancer (NSCLC) patients (N = 125) treated with first-line platinum-based chemotherapy. RT-qPCR was used to analyze miRNA expression levels in the plasma of patients prior to treat ...[more]

PMID: 34440757

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Project description:BackgroundThe homeobox A9 gene encodes a transcription factor, and aberrantly methylated homeobox A9 in the circulation has been suggested as a prognostic marker in early stage non-small cell lung cancer (NSCLC). The aim of the present study was to investigate the prognostic impact of methylated homeobox A9 in plasma from patients with advanced NSCLC.MethodsBlood samples were prospectively collected from patients with NSCLC stage III and IV receiving standard first line chemotherapy. Sampling took place before treatment initiation and subsequently before each treatment cycle. Plasma was stored at -80 °C until analysis. DNA was extracted, and following bisulfite conversion methylated homeobox A9 was analyzed by methylation specific droplet digital polymerase chain reaction. Detection of methylated homeobox A9 was assessed as a binary variable. The primary endpoint was overall survival (OS).ResultsA total of 231 patients were included. At baseline methylated homeobox A9 was detected in 78.5% of the patients with a clear correlation to survival. The median OS for patients with and without detectable methylated homeobox A9 was 7.4 and 11.1 months, respectively [hazard ratio (HR) 1.79, 95% confidence interval (CI): 1.35-2.38, P<0.001]. The difference increased after the first cycle of treatment. At this time point the median OS was 6.2 and 15.6 months for patients with and without detectable methylated homeobox A9, respectively (HR 2.07, 95% CI: 1.58-2.73, P<0.001). The independent prognostic impact of detectable methylated homeobox A9 after one treatment cycle assessed by multiple Cox regression including known prognostic factors resulted in a HR of 3.79 (2.19-6.54, P<0.001) compared to undetectable methylated homeobox A9.ConclusionsMeasurable methylated homeobox A9 after the first treatment cycle may serve as a valuable prognostic marker in patients with advanced NSCLC. Routine clinical application with treatment reconsideration calls for further studies, preferably in prospective clinical trials.

Project description:BackgroundMicroRNAs (miRNAs) have been found to play an important role in the development and outcomes for multiple human cancers. Their role as a prognostic biomarker in non-small-cell lung cancer (NSCLC) remains unclear. This meta-analysis aims to clarify the role of various miRNAs in the survival of NSCLC patients.Materials and methodsAll studies were identified through medical database search engines. A meta-analysis was conducted to assess the correlation between miRNAs expressions and overall survival among those NSCLC studies. Relevant data were extracted from each eligible study regarding baseline characteristics and key statistics such as hazard ratio (HR), 95% confidence interval (CI), and P value, which were utilized to calculate a pooled effect size.ResultThirty-two studies were included in the meta-analysis. Using a random effect model, the combined HR and 95% CI for overall survival (OS) was calculated as 1.59 (1.39-1.82), predicting a poor overall survival. Five miRNAs (miR-21, miR-155, miR-let-7, miR-148a, and miR-148b) were found to be of significance for predicting OS in at least two studies, hence, selected for subgroup analysis. Subgroup analysis disclosed that elevated levels of miR-21 and miR-155 in both cancer tissue and blood samples were associated with worse OS. Compared to American studies (I-squared: <0.001% and P value: 0.94), Asian and European studies exhibited greater heterogeneity in miRNA expression and relationship to OS (I-squared, P values were approximately 78.85%, <0.001 and 61.28%, 0.006, respectively). These subgroup analyses also highlighted that elevated expression of miR-21 and miR-155 and low levels of expression of miR-148a, miR-148b, and miR-let-7 were associated with poor prognosis in NSCLC.ConclusionmiR-21, miR-155, miR-148a, miR-148b, and miR-let-7 are consistently up- or downregulated in NSCLC and are associated with poor OS. These miRNAs show potential as useful prognostic biomarkers in the diagnosis, treatment, and follow-up of NSCLC.

Dataset Information

A Prognostic Role for Circulating microRNAs Involved in Macrophage Polarization in Advanced Non-Small Cell Lung Cancer.

Publications

A Prognostic Role for Circulating microRNAs Involved in Macrophage Polarization in Advanced Non-Small Cell Lung Cancer.

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