Discriminating Potential Genetic Markers for Complete Response and Non-Complete Response Patients to Neoadjuvant Chemotherapy with Locally Advanced Rectal Cancer

Jaya Bagaria, Kyung-Ok Kim, Eva Bagyinszky, Seong Soo A. An and Jeong-Heum Baek
Additional contact information
Jaya Bagaria: Department of Bionano Technology, Gachon University, Seongnam-si 13120, Korea
Kyung-Ok Kim: Gachon Medical Research Institute, Gil Medical Center, Gachon University, Incheon 21565, Korea
Eva Bagyinszky: Department of Bionano Technology, Gachon University, Seongnam-si 13120, Korea
Seong Soo A. An: Department of Bionano Technology, Gachon University, Seongnam-si 13120, Korea
Jeong-Heum Baek: Division of Colon and Rectal Surgery, Department of Surgery, Gil Medical Center, College of Medicine, Gachon University, Incheon 21565, Korea

IJERPH, 2022, vol. 19, issue 7, 1-12

Abstract: Background: Neoadjuvant chemoradiotherapy (nCRT) prior to surgery is considered standard therapy for locally advanced rectal cancer. Unfortunately, most patients with rectal cancer are resistant to radiotherapy. This might be a genetic cause. The role of certain rectal cancer-causing genes has not been completely elucidated. This study aims to investigate the genes responsible for locally advanced rectal cancer patients not reacting to radiotherapy. Methods: Whole exome sequencing of the DNA samples was performed on the samples. Bioinformatic analysis on the subjects was established. Individual genetic information was screened to identify differently expressed genes that more frequently appeared in non-complete response (NCR) compared to complete response (CR) patients after nCRT. All variations were verified by Sanger sequencing. Results: Genotyping information and pathway analyses of the samples indicated genes such as FLCN, CALML5, and ANTXR1 to be commonly mutated in CR group, whereas genes such as GALNTL14, CNKSR1, ACD, and CUL3 were more commonly mutated in the NCR group. Chi-square test revealed some significant variants (<0.05) such as rs3744124 (FLCN), rs28365986 (ANTXR1), rs10904516 (CALML5), rs3738952 (CUL3), rs13394 and rs2293013 (PIH1D1), rs2274531 (GPA33), rs4963048 (BRSK2), rs17883366 (IL3RA), rs2297575 (PSMD5), rs2288101 (GALNT14), and rs11954652 (DCTN4). Conclusion: Identifying an array of genes that separate NCRs from CRs would lead to finding genetic biomarkers for early detection of rectal cancer patients that are resistant to nCRT. A further investigation to validate the significance of genetic biomarkers to segregate NCRs from CRs should be performed with a larger CRC dataset. Protein expression levels, as well as transcriptomic analysis, would also help us understand the mechanism of how these genes could play a role in preventing radiation therapy to patients. This would be essential to prevent redundant radiation therapy.

Keywords: rectal cancer; genetic biomarker; whole exome sequencing; bioinformatic analysis (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2022
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