Analysis of KRAS, NRAS, and BRAF Mutations, Microsatellite Instability, and Relevant Prognosis Effects in Patients With Early Colorectal Cancer: A Cohort Study in East Asia

BackgroundEarly colorectal cancer (ECRC) refers to any size of colorectal cancer (CRC) whose depth of invasion is limited to the mucosa and submucosa. About 10% of patients with ECRC die from cancer after surgery. KRAS, NRAS, and BRAF mutations and microsatellite instability (MSI) are considered dia...

Full description

Bibliographic Details
Main Authors: Yang Li, Jun Xiao, Tiancheng Zhang, Yanying Zheng, Hailin Jin
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-06-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.897548/full
_version_ 1818547107838033920
author Yang Li
Jun Xiao
Tiancheng Zhang
Yanying Zheng
Hailin Jin
author_facet Yang Li
Jun Xiao
Tiancheng Zhang
Yanying Zheng
Hailin Jin
author_sort Yang Li
collection DOAJ
description BackgroundEarly colorectal cancer (ECRC) refers to any size of colorectal cancer (CRC) whose depth of invasion is limited to the mucosa and submucosa. About 10% of patients with ECRC die from cancer after surgery. KRAS, NRAS, and BRAF mutations and microsatellite instability (MSI) are considered diagnostic and prognostic markers in CRC. However, their characteristics in ECRC and whether postoperative chemotherapy based on them will benefit ECRC patients or not remain unknown.Patients and MethodsPatients with ECRC and 298 patients with advanced colorectal cancer (ACRC) were collected in our hospital from January 2013 to December 2015. The Amplification Refractory Mutation System (ARMS)-PCR was used to perform the KRAS, NRAS, and BRAF mutant tests.ResultsIn ECRC patients, 43 cases of KRAS mutation were found, accounting for 69.35%. Interestingly, among KRAS mutations, there were 10 KRAS multi-site mutation patients (16.13% in 62 ECRC patients). Moreover, the NRAS mutation rate was 3.23% but no BRAF mutation was found and only 1 case of MSI-High was detected. KRAS mutation was only related to the depth of tumor invasion whereas KRAS multi-site mutations were related to mucus components and tumor size. As far as NRAS is concerned, mutations were associated with elevated CEA, mucus components, and the depth of tumor invasion. Notably, compared with 2.35% KRAS multi-site mutation in ACRC, the rate of KRAS multi-site mutation in ECRC was much higher. Furthermore, Cox regression analysis revealed that KRAS mutation could be an independent prognostic factor of ECRC in patients who have undergone endoscopic resection or surgery.ConclusionPatients with ECRC might benefit from KRAS mutation testing but not from postoperative chemotherapy.
first_indexed 2024-12-12T08:02:15Z
format Article
id doaj.art-21206ae7a88b4dc5bce534fc4a980d08
institution Directory Open Access Journal
issn 2234-943X
language English
last_indexed 2024-12-12T08:02:15Z
publishDate 2022-06-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Oncology
spelling doaj.art-21206ae7a88b4dc5bce534fc4a980d082022-12-22T00:32:06ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-06-011210.3389/fonc.2022.897548897548Analysis of KRAS, NRAS, and BRAF Mutations, Microsatellite Instability, and Relevant Prognosis Effects in Patients With Early Colorectal Cancer: A Cohort Study in East AsiaYang Li0Jun Xiao1Tiancheng Zhang2Yanying Zheng3Hailin Jin4Gastroenterology Endoscopy Center, Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing, ChinaGastroenterology Endoscopy Center, Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing, ChinaGastroenterology Endoscopy Center, Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing, ChinaDepartment of Pathology, Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing, ChinaGastroenterology Endoscopy Center, Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing, ChinaBackgroundEarly colorectal cancer (ECRC) refers to any size of colorectal cancer (CRC) whose depth of invasion is limited to the mucosa and submucosa. About 10% of patients with ECRC die from cancer after surgery. KRAS, NRAS, and BRAF mutations and microsatellite instability (MSI) are considered diagnostic and prognostic markers in CRC. However, their characteristics in ECRC and whether postoperative chemotherapy based on them will benefit ECRC patients or not remain unknown.Patients and MethodsPatients with ECRC and 298 patients with advanced colorectal cancer (ACRC) were collected in our hospital from January 2013 to December 2015. The Amplification Refractory Mutation System (ARMS)-PCR was used to perform the KRAS, NRAS, and BRAF mutant tests.ResultsIn ECRC patients, 43 cases of KRAS mutation were found, accounting for 69.35%. Interestingly, among KRAS mutations, there were 10 KRAS multi-site mutation patients (16.13% in 62 ECRC patients). Moreover, the NRAS mutation rate was 3.23% but no BRAF mutation was found and only 1 case of MSI-High was detected. KRAS mutation was only related to the depth of tumor invasion whereas KRAS multi-site mutations were related to mucus components and tumor size. As far as NRAS is concerned, mutations were associated with elevated CEA, mucus components, and the depth of tumor invasion. Notably, compared with 2.35% KRAS multi-site mutation in ACRC, the rate of KRAS multi-site mutation in ECRC was much higher. Furthermore, Cox regression analysis revealed that KRAS mutation could be an independent prognostic factor of ECRC in patients who have undergone endoscopic resection or surgery.ConclusionPatients with ECRC might benefit from KRAS mutation testing but not from postoperative chemotherapy.https://www.frontiersin.org/articles/10.3389/fonc.2022.897548/fullKRASNRASBRAFmicrosatellite instabilitygene mutationearly colorectal cancer
spellingShingle Yang Li
Jun Xiao
Tiancheng Zhang
Yanying Zheng
Hailin Jin
Analysis of KRAS, NRAS, and BRAF Mutations, Microsatellite Instability, and Relevant Prognosis Effects in Patients With Early Colorectal Cancer: A Cohort Study in East Asia
Frontiers in Oncology
KRAS
NRAS
BRAF
microsatellite instability
gene mutation
early colorectal cancer
title Analysis of KRAS, NRAS, and BRAF Mutations, Microsatellite Instability, and Relevant Prognosis Effects in Patients With Early Colorectal Cancer: A Cohort Study in East Asia
title_full Analysis of KRAS, NRAS, and BRAF Mutations, Microsatellite Instability, and Relevant Prognosis Effects in Patients With Early Colorectal Cancer: A Cohort Study in East Asia
title_fullStr Analysis of KRAS, NRAS, and BRAF Mutations, Microsatellite Instability, and Relevant Prognosis Effects in Patients With Early Colorectal Cancer: A Cohort Study in East Asia
title_full_unstemmed Analysis of KRAS, NRAS, and BRAF Mutations, Microsatellite Instability, and Relevant Prognosis Effects in Patients With Early Colorectal Cancer: A Cohort Study in East Asia
title_short Analysis of KRAS, NRAS, and BRAF Mutations, Microsatellite Instability, and Relevant Prognosis Effects in Patients With Early Colorectal Cancer: A Cohort Study in East Asia
title_sort analysis of kras nras and braf mutations microsatellite instability and relevant prognosis effects in patients with early colorectal cancer a cohort study in east asia
topic KRAS
NRAS
BRAF
microsatellite instability
gene mutation
early colorectal cancer
url https://www.frontiersin.org/articles/10.3389/fonc.2022.897548/full
work_keys_str_mv AT yangli analysisofkrasnrasandbrafmutationsmicrosatelliteinstabilityandrelevantprognosiseffectsinpatientswithearlycolorectalcanceracohortstudyineastasia
AT junxiao analysisofkrasnrasandbrafmutationsmicrosatelliteinstabilityandrelevantprognosiseffectsinpatientswithearlycolorectalcanceracohortstudyineastasia
AT tianchengzhang analysisofkrasnrasandbrafmutationsmicrosatelliteinstabilityandrelevantprognosiseffectsinpatientswithearlycolorectalcanceracohortstudyineastasia
AT yanyingzheng analysisofkrasnrasandbrafmutationsmicrosatelliteinstabilityandrelevantprognosiseffectsinpatientswithearlycolorectalcanceracohortstudyineastasia
AT hailinjin analysisofkrasnrasandbrafmutationsmicrosatelliteinstabilityandrelevantprognosiseffectsinpatientswithearlycolorectalcanceracohortstudyineastasia