KRAS and PIK3CA bi-mutations predict a poor prognosis in colorectal cancer patients: A single-site report

Study rationale: The coexistence of KRAS and PIK3CA mutations in cells implies potential synergistic hyperactivation of the Ras/MAPK and PI3K/Akt oncogenic pathways. Therefore, it is desirable to investigate the concomitant mutations of KRAS and PIK3CA in colorectal cancer (CRC) samples and whether...

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Main Authors: Qianxin Luo, Dianke Chen, Xinjuan Fan, Xinhui Fu, Tenghui Ma, Daici Chen
Format: Article
Language:English
Published: Elsevier 2020-12-01
Series:Translational Oncology
Online Access:http://www.sciencedirect.com/science/article/pii/S1936523320303661
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record_format Article
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language English
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author Qianxin Luo
Dianke Chen
Xinjuan Fan
Xinhui Fu
Tenghui Ma
Daici Chen
spellingShingle Qianxin Luo
Dianke Chen
Xinjuan Fan
Xinhui Fu
Tenghui Ma
Daici Chen
KRAS and PIK3CA bi-mutations predict a poor prognosis in colorectal cancer patients: A single-site report
Translational Oncology
author_facet Qianxin Luo
Dianke Chen
Xinjuan Fan
Xinhui Fu
Tenghui Ma
Daici Chen
author_sort Qianxin Luo
title KRAS and PIK3CA bi-mutations predict a poor prognosis in colorectal cancer patients: A single-site report
title_short KRAS and PIK3CA bi-mutations predict a poor prognosis in colorectal cancer patients: A single-site report
title_full KRAS and PIK3CA bi-mutations predict a poor prognosis in colorectal cancer patients: A single-site report
title_fullStr KRAS and PIK3CA bi-mutations predict a poor prognosis in colorectal cancer patients: A single-site report
title_full_unstemmed KRAS and PIK3CA bi-mutations predict a poor prognosis in colorectal cancer patients: A single-site report
title_sort kras and pik3ca bi-mutations predict a poor prognosis in colorectal cancer patients: a single-site report
publisher Elsevier
series Translational Oncology
issn 1936-5233
publishDate 2020-12-01
description Study rationale: The coexistence of KRAS and PIK3CA mutations in cells implies potential synergistic hyperactivation of the Ras/MAPK and PI3K/Akt oncogenic pathways. Therefore, it is desirable to investigate the concomitant mutations of KRAS and PIK3CA in colorectal cancer (CRC) samples and whether the concomitant mutations are associated with a poor prognosis in CRC patients. Aim: To investigate the clinicpathological characteristics and prognostic value of concomitant mutations of KRAS and PIK3CA in CRC samples. Methods: In this study, a total of 655 CRC patients from the Sixth Affiliated Hospital of Sun Yat-sen University were enrolled from January to December 2015. Sanger sequencing was applied to survey the mutational status of hotspot regions in the open reading frames (ORFs) of the KRAS and PIK3CA genes. Clinicpathological parameters were collected and analyzed. The Kaplan-Meier method and Cox regression model were applied to determine the correlation between the KRAS and PIK3CA mutation statuses and survival. Results: We found that KRAS and PIK3CA bi-mutations were significantly associated with aggressive clinicpathological features. Among the studied CRC patients, those with either KRAS mutations (P = 0.004) or KRAS and PIK3CA bi-mutations (P = 0.033) had poor overall survival (OS). In the multivariable analysis, KRAS mutations in exons 3 and 4 but not exon 2 with concomitant PIK3CA mutations were associated with a high risk of death (univariate HR = 8.05; 95% CI, 1.926–33.64, P = 0.004; multivariate HR = 10.505; 95% CI, 2.304–47.905, P = 0.002). Conclusion: The concomitant mutation statuses of KRAS and PIK3CA should be considered when the prognostic value of gene mutations is consulted in CRC patients.
url http://www.sciencedirect.com/science/article/pii/S1936523320303661
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spelling doaj-c829a71d95c1465d9f03c07b8901e2522020-11-25T03:00:08ZengElsevierTranslational Oncology1936-52332020-12-011312100874KRAS and PIK3CA bi-mutations predict a poor prognosis in colorectal cancer patients: A single-site reportQianxin Luo0Dianke Chen1Xinjuan Fan2Xinhui Fu3Tenghui Ma4Daici Chen5Guangdong Institute of Gastroenterology, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, China; Department of Intensive Care Unit, the Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, ChinaDepartment of Medical Oncology, the Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, ChinaGuangdong Institute of Gastroenterology, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, China; Department of Pathology, the Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, ChinaGuangdong Institute of Gastroenterology, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, China; Department of Pathology, the Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, ChinaDepartment of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, ChinaGuangdong Institute of Gastroenterology, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, China; Department of Clinical Laboratory, the Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, China; Corresponding author at: Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Gastrointestinal Institute of Gastroenterology and the Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, China.Study rationale: The coexistence of KRAS and PIK3CA mutations in cells implies potential synergistic hyperactivation of the Ras/MAPK and PI3K/Akt oncogenic pathways. Therefore, it is desirable to investigate the concomitant mutations of KRAS and PIK3CA in colorectal cancer (CRC) samples and whether the concomitant mutations are associated with a poor prognosis in CRC patients. Aim: To investigate the clinicpathological characteristics and prognostic value of concomitant mutations of KRAS and PIK3CA in CRC samples. Methods: In this study, a total of 655 CRC patients from the Sixth Affiliated Hospital of Sun Yat-sen University were enrolled from January to December 2015. Sanger sequencing was applied to survey the mutational status of hotspot regions in the open reading frames (ORFs) of the KRAS and PIK3CA genes. Clinicpathological parameters were collected and analyzed. The Kaplan-Meier method and Cox regression model were applied to determine the correlation between the KRAS and PIK3CA mutation statuses and survival. Results: We found that KRAS and PIK3CA bi-mutations were significantly associated with aggressive clinicpathological features. Among the studied CRC patients, those with either KRAS mutations (P = 0.004) or KRAS and PIK3CA bi-mutations (P = 0.033) had poor overall survival (OS). In the multivariable analysis, KRAS mutations in exons 3 and 4 but not exon 2 with concomitant PIK3CA mutations were associated with a high risk of death (univariate HR = 8.05; 95% CI, 1.926–33.64, P = 0.004; multivariate HR = 10.505; 95% CI, 2.304–47.905, P = 0.002). Conclusion: The concomitant mutation statuses of KRAS and PIK3CA should be considered when the prognostic value of gene mutations is consulted in CRC patients.http://www.sciencedirect.com/science/article/pii/S1936523320303661