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

• Published in: International journal of environmental research and public health Vol. 19; no. 7; p. 4008
• Main Authors: Bagaria, Jaya, Kim, Kyung-Ok, Bagyinszky, Eva, An, Seong Soo A, Baek, Jeong-Heum
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.03.2022; MDPI
• Subjects: Apoptosis; Biomarkers; Cancer; Cancer therapies; Chemoradiotherapy; Chemotherapy; Chi-square test; Colorectal cancer; DNA sequencing; Genes; Genetic Markers; Genomes; Genotyping; Humans; Kinases; Microfilament Proteins - genetics; Mutation; Neoadjuvant Therapy; Neoplasms, Second Primary; Patients; Radiation; Radiation therapy; Receptors, Cell Surface - genetics; Rectal Neoplasms - genetics; Rectal Neoplasms - therapy; Rectum; Statistical tests; Transcriptomics; Treatment Outcome; bioinformatic analysis; genetic biomarker; whole exome sequencing; rectal cancer
• ISSN: 1660-4601; 1661-7827; 1660-4601
• DOI: 10.3390/ijerph19074008

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.