Retrospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Apr 16, 2021; 9(11): 2458-2468
Published online Apr 16, 2021. doi: 10.12998/wjcc.v9.i11.2458
Relationship between mismatch repair protein, RAS, BRAF, PIK3CA gene expression and clinicopathological characteristics in elderly colorectal cancer patients
Jun-Zhen Fan, Gao-Fei Wang, Xue-Bin Cheng, Zhou-Huan Dong, Xin Chen, Yu-Jiao Deng, Xin Song
Jun-Zhen Fan, Gao-Fei Wang, Xue-Bin Cheng, Zhou-Huan Dong, Xin Chen, Xin Song, Department of Pathology, First Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100853, China
Yu-Jiao Deng, Department of Ultrasound, First Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100853, China
Author contributions: Fan JZ, Wang GF and Cheng XB made equal contributions to this article, they analyzed the data and drafted the paper; Dong ZH, Chen X and Deng YJ revised the paper; Song X analyzed the data, revised and finalized the paper.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Chinese PLA General Hospital (Approval No. S2020-319-01).
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: All authors declare no conflicts of interest related to this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xin Song, MM, Associate Chief Technician, Department of Pathology, First Medical Center, Chinese People's Liberation Army General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, China. sxin66@hotmail.com
Received: December 22, 2020
Peer-review started: December 22, 2020
First decision: January 10, 2021
Revised: January 12, 2021
Accepted: February 1, 2021
Article in press: February 1, 2021
Published online: April 16, 2021
Abstract
BACKGROUND

Colorectal cancer (CRC) is common in elderly patients. Mismatch repair (MMR) protein deletion is one of the causes of CRC. The RAS (KRAS/NRAS), BRAF, and PIK3CA genes are important gene targets in CRC treatment and are closely related to the prognosis and survival of patients. However, little is known regarding the relationship between the expression of MMR, RAS, BRAF, PIK3CA and the clinicopathological features in CRC patients.

AIM

To analyze the relationship between the expression of MMR, RAS, BRAF, PIK3CA and the clinicopathological features in CRC.

METHODS

A total of 327 elderly patients with CRC were enrolled, and immuno-histochemistry was used to detect the MMR protein. Real-time quantitative polymerase chain reaction was used to detect the RAS (KRAS/NRAS), BRAF, and PIK3CA genes. The clinicopathological data of the patients were recorded and analyzed by SPSS 19.0 statistical software.

RESULTS

In 327 elderly patients with CRC, the rate of MMR protein loss was 9.79% (32/327), and the deletion rate of four MMR proteins (MSH2, MSH6, MLH1, PMS2) was 1.83% (6/327), 3.06% (10/327), 7.65% (25/327), and 7.65% (25/327), respectively. There were no significant differences between MMR protein deletion and sex, pathological type, tumor morphology, differentiation degree or lymph node metastasis (P > 0.05), but there was a significant difference between MMR protein deletion and tumor diameter and tumor location (P = 0.048/P = 0.000). The mutation rates of the KRAS, NRAS, BRAF and PIK3CA genes in elderly CRC patients were 44.95% (147/327), 2.45% (8/327), 3.36% (11/327) and 2.75% (9/327), respectively; the KRAS gene mutation was closely related to tumor morphology (P = 0.002) but not to other clinicopathological features (P > 0.05), and there were no significant differences between NRAS gene mutation and clinicopathological features (P > 0.05). The BRAF gene mutation showed a significant difference in pathological type, tumor location, differentiation degree and lymph node metastasis (P < 0.05), but was not correlated with sex, tumor size and tumor morphology (P > 0.05). The PIK3CA gene mutation showed no significant differences in the above clinicopathological characteristics (P > 0.05). Significant differences were observed between MMR protein deletion and KRAS, BRAF, and PIK3CA gene mutations in elderly CRC patients (P = 0.044, P = 0.000, P = 0.003, respectively), but there was no significant difference between MMR protein deletion and NRAS mutation (P > 0.05).

CONCLUSION

In elderly CRC patients, the tumor is mainly located in the right colon, and the deletion rate of MMR protein is higher when the tumor diameter is greater than or equal to 5 cm; the deletion rate of MLH1 and PMS2 is more common; the mutation rate of KRAS gene is higher than that of the NRAS, BRAF and PIK3CA genes, the BRAF gene mutation has different degrees of correlation with clinicopathological characteristics; when the MMR protein is deleted, the BRAF and PIK3CA gene mutations are often present, and the KRAS gene mutation rate is low.

Keywords: Elderly patients, Colorectal cancer, Mismatch repair protein, Gene mutation, Expression, Diagnosis

Core Tip: The mismatch repair (MMR) protein deletion is one of the causes of colorectal cancer (CRC). The RAS (KRAS/NRAS), BRAF, and PIK3CA genes are important gene targets in CRC treatment and are closely related to the prognosis and survival of patients. However, little is known regarding the relationship between the expression of MMR, RAS, BRAF, PIK3CA and the clinicopathological features in CRC patients. In this study, we analyzed four target genes to provide a further theoretical basis for clinicians in relation to the diagnosis, treatment and prognosis of CRC.