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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Potential Molecular Markers for Cholecystic Inflammation-Induced Carcinogenesis Based on RNA-Seq Gene Screening

In Press, (this is not the final "Version of Record"). Available online 23 April, 2024
Author(s): Henghai Yu, Peng Chen, Ying Hu, Feng Liu, Xiaoping Wei* and Mingdao Hu*
Published on: 23 April, 2024

DOI: 10.2174/0113862073287686240409082130

Abstract

Background: Uncontrolled inflammation plays an important role in the initiation and progression of tumors. The repeated circulation and continuous stimulation of gallbladder epithelium caused by gallstones is an important risk factor for gallbladder cancer.

Methods: To study pathogenesis, samples were collected for chronic cholecystitis caused by gallstones and early and advanced gallbladder cancer with gallstones and subjected to RNA-seq analysis. Gene Ontology and Kyoto Gene and Genome Encyclopedia analyses were used to elucidate the protein–protein interaction network and identify differentially expressed genes.

Results: Nine potential molecular markers, VTN, CHAD, AKR1C4, ABCC2, AOX1, ADH1A, ADH1C, PLA2G2A, and CYP4F3, with elevated expression gradients in cholecystitis and early and advanced gallbladder cancer, were identified. Using qPCR and immunohistochemistry on clinical tissues, we confirmed three factors, VTN, CYP4F3, and AOX1, to be worthy of further research. To demonstrate that these three genes are potential molecular markers for gallbladder cancer, their cellular biological functions were confirmed in gallbladder cancer cell lines through siRNA transfection.

Conclusion: The potential molecular markers CYP4F3, VTN, and AOX1 for cholecystitis and different stages of gallbladder cancer were identified. Further studies on differentially expressed genes vital in gallbladder cancer progression can help provide potential targets for the early diagnosis and treatment of gallbladder cancer.

Keywords: Gallbladder cancer, RNA sequencing, inflammation-induced carcinogenesis, uncontrolled inflammation, molecular marker, cholecystitis.


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