Affiliation:
1. Student Research Committee, Department of Medical Genetics Shahid Beheshti University of Medical Sciences Tehran Iran
2. Department of Cell and Molecular Biology and Microbiology, Faculty of Science and Technology University of Isfahan Isfahan Iran
3. Department of Medical Genetics Shahid Beheshti University of Medical Sciences Tehran Iran
4. Department of Biotechnology and Plant Breeding Islamic Azad University Science and Research Branch Tehran Iran
5. Bayesian Imaging and Spatial Statistics Group, Institute of Statistics Ludwig‐Maximilian‐Universität München Munich Germany
6. Department of Statistics Lorestan University Khorramabad Iran
7. Urogenital Stem Cell Research Center Shahid Beheshti University of Medical Sciences Tehran Iran
Abstract
AbstractBackgroundLung cancer is a major cause of cancer‐related mortality worldwide, with a 5‐year survival rate of approximately 22%. Cisplatin is one of the standard first‐line chemotherapeutic agents for non‐small cell lung cancer (NSCLC), but its efficacy is often limited by the development of resistance. Despite extensive research on the molecular mechanisms of chemoresistance, the underlying causes remain elusive and complex.AimsWe analyzed three microarray datasets to find the gene signature and key pathways related to cisplatin resistance in NSCLC.Methods and ResultsWe compared the gene expression of sensitive and resistant NSCLC cell lines treated with cisplatin. We found 274 DEGs, including 111 upregulated and 163 downregulated genes, in the resistant group. Gene set enrichment analysis showed the potential roles of several DEGs, such as TUBB2B, MAPK7, TUBAL3, MAP2K5, SMUG1, NTHL1, PARP3, NTRK1, G6PD, PDK1, HEY1, YTHDF2, CD274, and MAGEA1, in cisplatin resistance. Functional analysis revealed the involvement of pathways, such as gap junction, base excision repair, central carbon metabolism, and Notch signaling in the resistant cell lines.ConclusionWe identified several molecular factors that contribute to cisplatin resistance in NSCLC cell lines, involving genes and pathways that regulate gap junction communication, DNA damage repair, ROS balance, EMT induction, and stemness maintenance. These genes and pathways could be targets for future studies to overcome cisplatin resistance in NSCLC.
Funder
Student Research Committee, Tabriz University of Medical Sciences