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; Jeong-Heum Baek

doi:10.3390/ijerph19074008

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

Int J Environ Res Public Health. 2022 Mar 28;19(7):4008. doi: 10.3390/ijerph19074008.

Authors

Jaya Bagaria¹, Kyung-Ok Kim², Eva Bagyinszky¹, Seong Soo A An¹, Jeong-Heum Baek³

Affiliations

¹ Department of Bionano Technology, Gachon University, Seongnam-si 13120, Korea.
² Gachon Medical Research Institute, Gil Medical Center, Gachon University, Incheon 21565, Korea.
³ Division of Colon and Rectal Surgery, Department of Surgery, Gil Medical Center, College of Medicine, Gachon University, Incheon 21565, Korea.

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: bioinformatic analysis; genetic biomarker; rectal cancer; whole exome sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chemoradiotherapy
Genetic Markers
Humans
Microfilament Proteins / genetics
Neoadjuvant Therapy
Neoplasms, Second Primary*
Receptors, Cell Surface / genetics
Rectal Neoplasms* / genetics
Rectal Neoplasms* / therapy
Treatment Outcome

Substances

ANTXR1 protein, human
Genetic Markers
Microfilament Proteins
Receptors, Cell Surface