KRAS and PIK3CA bi-mutations predict a poor prognosis in colorectal cancer patients: A single-site report.
KRAS and PIK3CA bi-mutations predict a poor prognosis in colorectal cancer patients: A single-site report.
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DOI：
10.1016/j.tranon.2020.100874
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发表时间：
2020-12
影响因子：
5
通讯作者：
Chen D
中科院分区：
文献类型：
--
作者：
Luo Q;Chen D;Fan X;Fu X;Ma T;Chen D
细胞中KRAS和PIK 3CA突变的共存意味着Ras/MAPK和PI 3 K/Akt致癌途径的潜在协同超活化。因此，需要研究结直肠癌（CRC）样品中KRAS和PIK 3CA的伴随突变以及伴随突变是否与CRC患者的不良预后相关。探讨KRAS和PIK 3CA基因突变在结直肠癌中的临床病理特征及预后价值。本研究于2015年1月至12月在中山大学附属第六医院共入组了655例CRC患者。应用桑格测序法调查KRAS和PIK 3CA基因开放阅读框（ORF）中热点区域的突变状态。收集并分析临床病理参数。采用Kaplan-Meier方法和考克斯回归模型确定KRAS和PIK 3CA突变状态与生存率之间的相关性。我们发现KRAS和PIK 3CA双突变与侵袭性临床病理特征显著相关。在研究的CRC患者中，具有KRAS突变（P = 0.004）或KRAS和PIK 3CA双突变（P = 0.033）的患者的总生存期（OS）较差。在多变量分析中，外显子3和4中的KRAS突变（而非外显子2）伴随PIK 3CA突变与死亡风险高相关（单变量HR = 8.05; 95% CI，1.926-33.64，P = 0.004;多变量HR = 10.505; 95% CI，2.304-47.905，P = 0.002）。当咨询CRC患者基因突变的预后价值时，应考虑KRAS和PIK 3CA的伴随突变状态。
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. To investigate the clinicpathological characteristics and prognostic value of concomitant mutations of KRAS and PIK3CA in CRC samples. 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. 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). The concomitant mutation statuses of KRAS and PIK3CA should be considered when the prognostic value of gene mutations is consulted in CRC patients.
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作者：
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