Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Luo Q

PROVIDER: S-EPMC7502368 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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

Luo Qianxin Q Chen Dianke D Fan Xinjuan X Fu Xinhui X Ma Tenghui T Chen Daici D

Translational oncology 20200916 12

<h4>Study rationale</h4>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.<h4>Aim</h4>To investigate the clinicpathological characteristics and prognostic value of concomitant mutations of ...[more]

PMID: 32947236

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Project description:BackgroundMutations in KRAS, BRAF and PIK3CA are the most common somatic alterations found in the colorectal cancer (CRC) patients from Western countries; but their prevalence and prognostic value have not been adequately assessed in Asian patients. The aim of this study was to determine the mutation frequencies of these genes in Chinese CRC patients and to investigate their impact on prognosis.MethodsThe sequences of exon 2 of KRAS, exon 15 of BRAF and exons 9 and 20 of PIK3CA were evaluated by PCR and direct sequencing using DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues from primary CRC tumors of 214 patients (colon/rectum: 126/88).ResultsKRAS, BRAF and PIK3CA mutations were identified in 44.9% (96/214), 4.2% (9/214) and 12.3% (26/212) CRCs, respectively. The most frequent mutations in KRAS, BRAF and PIK3CA were G12D, V600E and H1047R, respectively. All BRAF and 80.8% PIK3CA mutations were from colon cancer patients. BRAF V600E was associated with advanced TNM (P < 0.001), more distant metastases (P = 0.025), and worse overall survival (OS, P < 0.001; multivariate HR = 4.2, P = 0.004) in colon cancer patients. Compared with KRAS wt/BRAF wt CRC patients (N = 109), those with KRAS codon 13 mutations (N = 25) had significantly worse OS (P = 0.016; multivariate HR = 2.7, P = 0.011), whereas KRAS codon 12-mutated cases were not significantly associated with survival. Among the three most common KRAS mutations, G13D (N = 23) showed significant association with poor OS (P = 0.024; multivariate HR = 2.6, P = 0.016) compared with KRAS wt/BRAF wt patients.ConclusionOur findings indicate that PI3K/RAS-RAF signaling pathway genes are frequently mutated in Chinese CRC patients, but have different characteristics than found in Western patients. BRAF V600E is an independent prognostic factor for Chinese patients. Our finding that KRAS codon 13 mutations (in particular G13D) are associated with inferior survival in BRAF wild-type CRCs in Chinese patients was not reported thus far. Our data emphasizes the importance of prospective evaluation of molecular features in CRC patients, because a single mutation type may represent a distinct biologic effect and clinical implication.

Dataset Information

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

Publications

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

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