The Spectrum, Tendency and Predictive Value of PIK3CA Mutation in Chinese Colorectal Cancer Patients.
The Spectrum, Tendency and Predictive Value of PIK3CA Mutation in Chinese Colorectal Cancer Patients.
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DOI：
10.3389/fonc.2021.595675
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发表时间：
2021
影响因子：
4.7
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Fu X;Lin H;Fan X;Zhu Y;Wang C;Chen Z;Tan X;Huang J;Cai Y;Huang Y
PIK 3CA是结直肠癌中的高频突变基因，但其预后价值仍不清楚。本研究评估了中国CRC队列中西妥昔单抗治疗PIK 3CA的突变趋势、谱、预后能力和预测能力。采用桑格测序和高分辨率熔解试验检测5763例结直肠癌患者PIK 3CA第9和第20外显子的状态。分析5733例患者的临床病理特征。分别采用Kaplan-Meier法和诺模图评估总生存曲线和疾病复发。在13.4%（771/5733）的患者中检测到58种突变。从2014年到2018年，PIK 3CA的突变率从11.0%上升到13.5%。在IV期，20号外显子突变患者的总生存时间短于野生型患者（多变量考克斯回归分析，HR = 2.72，95% CI = 1.47-5.09; p值= 0.012）。在III期，PIK 3CA突变患者更可能复发（多变量Logistic回归分析，外显子9：OR = 2.54，95%CI = 1.34-4.73，p = 0.003;外显子20：OR = 3.89，95%CI = 1.66-9.10，p = 0.002）。预测III期患者复发风险的诺模图的一致性指数为0.685。西妥昔单抗治疗后，PIK 3CA外显子9野生型患者（n = 9）和突变型患者（n = 5）的中位PFS未达到显著差异（3.6个月vs. 2.3个月，对数秩检验，p值= 0.513）。我们发现PIK 3CA突变分别是IV期患者总生存率和III期患者复发的不良预测标志物。此外，我们认为PIK 3CA外显子9突变不是KRAS、NRAS和BRAF野生型mCRC患者接受西妥昔单抗治疗的阴性预测因子。
PIK3CA is a high-frequency mutation gene in colorectal cancer, while its prognostic value remains unclear. This study evaluated the mutation tendency, spectrum, prognosis power and predictive power in cetuximab treatment of PIK3CA in Chinese CRC cohort. The PIK3CA exon 9 and 20 status of 5763 CRC patients was detected with Sanger sequencing and a high-resolution melting test. Clinicopathological characteristics of 5733 patients were analyzed. Kaplan-Meier method and nomogram were used to evaluate the overall survival curve and disease recurrence, respectively. Fifty-eight types of mutations in 13.4% (771/5733) of the patients were detected. From 2014 to 2018, the mutation rate of PIK3CA increased from 11.0% to 13.5%. At stage IV, exon 20 mutated patients suffered shorter overall survival time than wild-type patients (multivariate COX regression analysis, HR = 2.72, 95% CIs = 1.47-5.09; p-value = 0.012). At stage III, PIK3CA mutated patients were more likely to relapse (multivariate Logistic regression analysis, exon 9: OR = 2.54, 95% CI = 1.34-4.73, p = 0.003; exon 20: OR = 3.89, 95% CI = 1.66-9.10, p = 0.002). The concordance index of the nomogram for predicting the recurrence risk of stage III patients was 0.685. After cetuximab treatment, the median PFS of PIK3CA exon 9 wild-type patients (n = 9) and mutant patients (n = 5) did not reach a significant difference (3.6 months vs. 2.3 months, Log-rank test, p-value = 0.513). We found that PIK3CA mutation was an adverse predictive marker for the overall survival of stage IV patients and recurrence of stage III patients, respectively. Further more, we suggested that PIK3CA exon 9 mutations are not negative predictors of cetuximab treatment in KRAS, NRAS, and BRAF wild-type mCRC patients.
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影响因子：
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DOI：
10.1073/pnas.0701005104
发表时间：
2007-03-27
影响因子：
11.1
作者：
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