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A bioinformatics-based study on the Cisplatin-resistant lung cancer cells; what are the orchestrators of this phenom?
Amirreza Khalaji1, Sara Haddad2, Yalda Yazdani3
1Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Abstract:
Lung cancer represents a significant global health issue and is among the central causes of mortality and morbidity around the world. Unfortunately, the majority of lung cancer patients acquire drug resistant to chemotherapy either intrinsically or acquired after Cisplatin treatment. It is indicated that increasing or decreasing the expression of particular genes can affect chemotherapeutic sensitivity or resistance. As a result, gaining a deeper knowledge of the changed expression of genes implicated in lung cancer drug resistance, as well as developing novel therapeutic techniques, are critical targets for continued advancement in lung cancer treatment. In the present study, we aimed to find key regulatory genes in the progression of Cisplatin resistance in A-549 lung cancer cells. In this regard, microarray dataset of Cisplatin-resistant and Cisplatin-sensitive was retrieved from the Gene Expression Omnibus (GEO) with accession number of GSE108214. Then, differentially expressed genes (DEGs) between sensitive and resistant lung cancer cells were obtained by using R software v4.0.2 and related packages. We recognized CEACAM1, DGKA, ARHGEF4, and THSD4 are involved in the drug resistance. Experimentally, Cisplatin-resistant A-549 cells were developed and analyzed by MTT assay. Besides, the expression of candidate genes were analyzed in these cells compared to Cisplatin-sensitive A-549 cells by qRT-PCR. The findings presented that the expression of CEACAM1, DGKA, ARHGEF4, and THSD4 was altered following the induction of Cisplatin resistance in A549 cells.
Insights
This study identified key genes, CEACAM1, DGKA, ARHGEF4, and THSD4, involved in lung cancer
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Lung cancer is a leading cause of mortality globally.
- Chemotherapy resistance, particularly to Cisplatin, is a major challenge in lung cancer treatment.
- Understanding gene expression changes is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To identify key regulatory genes associated with Cisplatin resistance in A-549 lung cancer cells.
- To investigate the differential gene expression profiles between Cisplatin-sensitive and resistant lung cancer cells.
Main Methods:
- Utilized a microarray dataset (GEO accession: GSE108214) for differential gene expression analysis.
- Employed R software (v4.0.2) and relevant packages to identify differentially expressed genes (DEGs).
- Developed Cisplatin-resistant A-549 cells and validated gene expression using MTT assay and qRT-PCR.
Main Results:
- Identified CEACAM1, DGKA, ARHGEF4, and THSD4 as genes implicated in Cisplatin resistance.
- Observed altered expression of these candidate genes in Cisplatin-resistant A-549 cells compared to sensitive cells.
Conclusions:
- CEACAM1, DGKA, ARHGEF4, and THSD4 are potential key regulators in the development of Cisplatin resistance in lung cancer.
- These findings contribute to a deeper understanding of lung cancer drug resistance mechanisms.

