The Role of MiR-544a in the Wnt/β-Catenin Pathway and its Association with Platinum-Based Chemotherapy Resistance in Advanced Non-Small Cell Lung Cancer

Abstract

Introduction

MicroRNAs (miR)-544a has been identified as a potential regulator in the Wnt/β-Catenin pathway, but its specific role in non-small cell lung cancer (NSCLC) and its relationship with platinum-based chemotherapy resistance, remains unclear. Thus, we aim to determine the relationship between the expression of miR-544a and GSK-3β, β-catenin, and CD44 with platinum-based chemotherapy resistance in advanced stage NSCLC patients.

Methods

The research is designed as a case control study in which individuals diagnosed with advanced stage (III-IV) NSCLC from January 2018 and July 2023 from 6 different hospitals in Indonesia.

The analysis of miR-544a levels was done using the real-time QuantiTect SYBR Green PCR Master Kit. The expression of GSK-3β, β-catenin, and CD44 expression using immunohistochemistry (IHC) staining was performed from the formalin-fixed paraffin embedded (FFPE). The evaluation of IHC intensity was divided into four expression categories: negative or unstained, weakly positive, moderately positive, and strongly positive. From 500 cells, we used the semi-quantitative H-score formula.

Results

This study of 62 advance NSCLC patients undergoing platinum-based chemotherapy and found miR-544a were higher in poor responders, with a significant p-value of 0.009. The predictive model for MiR-544a demonstrated a AUC value of 0.6957. A miR-544a cutoff value of 2.08 yielded sensitivity of 64% and specificity of 67.57%. MiR-544a levels above 2.08 were significantly associated with poorer treatment response (OR 2.159, 95% CI 1.132 - 4.117, p = 0.016).

Conclusions

The study demonstrates that miR-544a levels are a significant biomarker for predicting chemotherapy response in patients with advance NSCLC.