Association of various RAS codon mutations and prognostic outcomes of patients with colorectal liver metastases after hepatectomy
Abstract Purpose The prognostic and predictive value of RAS mutations in patients with colorectal liver metastases (CRLM) who have undergone hepatectomy holds substantial importance. The present study aimed to investigate the impact of different RAS codon mutations on long‐term survival in CRLM pati...
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| Format: | Article |
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Wiley
2024-10-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.70168 |
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| author | Xiao‐Gang Wu Wei Liu Yan‐Yan Wang Kun Wang Bao‐Cai Xing |
| author_facet | Xiao‐Gang Wu Wei Liu Yan‐Yan Wang Kun Wang Bao‐Cai Xing |
| author_sort | Xiao‐Gang Wu |
| collection | DOAJ |
| description | Abstract Purpose The prognostic and predictive value of RAS mutations in patients with colorectal liver metastases (CRLM) who have undergone hepatectomy holds substantial importance. The present study aimed to investigate the impact of different RAS codon mutations on long‐term survival in CRLM patients. Methods A retrospective analysis was conducted on clinicopathological data from 399 CRLM patients with RAS mutations who underwent hepatectomy between January 2000 and December 2020. The RAS mutation gene status was assessed in KRAS codons (G12, G13, Q61, and A146) and NRAS codons (G12, G13, and Q61). Survival curves were generated using the Kaplan–Meier plotter and compared using the log‐rank test. Univariate and multivariate analyses were performed to analyze the clinicopathological data. Results In the entire cohort, patients with KRAS G12 mutations exhibited the most favorable prognosis (p = 0.018). Comparatively, patients harboring KRAS Q61 mutations experienced poorer overall survival (OS) with a median of 15 months versus 33 months (p = 0.011) when compared to those with KRAS G12 mutations. Moreover, patients with NRAS Q61 mutations also showed decreased OS with a median of 26 months versus 33 months (p = 0.020) in comparison to KRAS G12 mutation patients. The results of multivariate analysis showed that both KRAS Q61 mutation (HR 2.130; 95% CI 1.088–4.168; p = 0.027) and NRAS Q61 mutation (HR 2.877; 95% CI 1.398–5.922; p = 0.004) were independent influencing factors of OS. Based on all identified risk factors, patients with RAS mutation were divided into high‐risk and low‐risk groups. Notably, in the high‐risk group, the incorporation of postoperative chemotherapy was associated with longer OS, while it did not improve the survival of patients in the low‐risk group. Conclusions KRAS Q61 and NRAS Q61 mutations are promising predictors for OS in CRLM patients after hepatectomy. Postoperative chemotherapy may significantly benefit CRLM patients with RAS mutations, particularly those identified as high‐risk. |
| format | Article |
| id | doaj-art-c6f75321a02940e1aef13cf4ceb68c30 |
| institution | OA Journals |
| issn | 2045-7634 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-c6f75321a02940e1aef13cf4ceb68c302025-08-20T02:32:11ZengWileyCancer Medicine2045-76342024-10-011319n/an/a10.1002/cam4.70168Association of various RAS codon mutations and prognostic outcomes of patients with colorectal liver metastases after hepatectomyXiao‐Gang Wu0Wei Liu1Yan‐Yan Wang2Kun Wang3Bao‐Cai Xing4State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Hepatopancreatobiliary Surgery Department I Peking University Cancer Hospital & Institute Beijing ChinaState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Hepatopancreatobiliary Surgery Department I Peking University Cancer Hospital & Institute Beijing ChinaState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Hepatopancreatobiliary Surgery Department I Peking University Cancer Hospital & Institute Beijing ChinaState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Hepatopancreatobiliary Surgery Department I Peking University Cancer Hospital & Institute Beijing ChinaState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Hepatopancreatobiliary Surgery Department I Peking University Cancer Hospital & Institute Beijing ChinaAbstract Purpose The prognostic and predictive value of RAS mutations in patients with colorectal liver metastases (CRLM) who have undergone hepatectomy holds substantial importance. The present study aimed to investigate the impact of different RAS codon mutations on long‐term survival in CRLM patients. Methods A retrospective analysis was conducted on clinicopathological data from 399 CRLM patients with RAS mutations who underwent hepatectomy between January 2000 and December 2020. The RAS mutation gene status was assessed in KRAS codons (G12, G13, Q61, and A146) and NRAS codons (G12, G13, and Q61). Survival curves were generated using the Kaplan–Meier plotter and compared using the log‐rank test. Univariate and multivariate analyses were performed to analyze the clinicopathological data. Results In the entire cohort, patients with KRAS G12 mutations exhibited the most favorable prognosis (p = 0.018). Comparatively, patients harboring KRAS Q61 mutations experienced poorer overall survival (OS) with a median of 15 months versus 33 months (p = 0.011) when compared to those with KRAS G12 mutations. Moreover, patients with NRAS Q61 mutations also showed decreased OS with a median of 26 months versus 33 months (p = 0.020) in comparison to KRAS G12 mutation patients. The results of multivariate analysis showed that both KRAS Q61 mutation (HR 2.130; 95% CI 1.088–4.168; p = 0.027) and NRAS Q61 mutation (HR 2.877; 95% CI 1.398–5.922; p = 0.004) were independent influencing factors of OS. Based on all identified risk factors, patients with RAS mutation were divided into high‐risk and low‐risk groups. Notably, in the high‐risk group, the incorporation of postoperative chemotherapy was associated with longer OS, while it did not improve the survival of patients in the low‐risk group. Conclusions KRAS Q61 and NRAS Q61 mutations are promising predictors for OS in CRLM patients after hepatectomy. Postoperative chemotherapy may significantly benefit CRLM patients with RAS mutations, particularly those identified as high‐risk.https://doi.org/10.1002/cam4.70168colorectal cancerhepatectomyliver metastasisprognosisRAS codon mutation |
| spellingShingle | Xiao‐Gang Wu Wei Liu Yan‐Yan Wang Kun Wang Bao‐Cai Xing Association of various RAS codon mutations and prognostic outcomes of patients with colorectal liver metastases after hepatectomy Cancer Medicine colorectal cancer hepatectomy liver metastasis prognosis RAS codon mutation |
| title | Association of various RAS codon mutations and prognostic outcomes of patients with colorectal liver metastases after hepatectomy |
| title_full | Association of various RAS codon mutations and prognostic outcomes of patients with colorectal liver metastases after hepatectomy |
| title_fullStr | Association of various RAS codon mutations and prognostic outcomes of patients with colorectal liver metastases after hepatectomy |
| title_full_unstemmed | Association of various RAS codon mutations and prognostic outcomes of patients with colorectal liver metastases after hepatectomy |
| title_short | Association of various RAS codon mutations and prognostic outcomes of patients with colorectal liver metastases after hepatectomy |
| title_sort | association of various ras codon mutations and prognostic outcomes of patients with colorectal liver metastases after hepatectomy |
| topic | colorectal cancer hepatectomy liver metastasis prognosis RAS codon mutation |
| url | https://doi.org/10.1002/cam4.70168 |
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