The Spectrum, Tendency and Predictive Value of PIK3CA Mutation in Chinese Colorectal Cancer Patients.

Xinhui Fu,Hanjie Lin,Xiaoli Tan,Yan Huang,Zhiting Chen,Xinjuan Fan,Chao Wang,Yacheng Cai,Jinglin Huang,Yaxi Zhu

doi:10.3389/fonc.2021.595675

Xinhui Fu, Hanjie Lin + Show 8 more

Open Access

https://doi.org/10.3389/fonc.2021.595675

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Abstract

Background 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.MethodsThe 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.ResultsFifty-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).ConclusionsWe 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.

Highlights

Colorectal cancer (CRC) is the third most prevalent malignancy worldwide, which leads to more than 860,000 deaths every year (1)
We found that PIK3CA mutation was a potential molecular biomarker for predicting resistance to 5-fluorouracil based chemotherapy regimens in stage III CRC patients
We found that about 13.4% of Chinese CRC patients carried PIK3CA mutation, 8.7% were at exon 9, 4.5% were at exon 20, and 0.2% were found at both exons

Summary

Introduction

Colorectal cancer (CRC) is the third most prevalent malignancy worldwide, which leads to more than 860,000 deaths every year (1). The significant predictive value of some genetic mutation status has been reported by various clinical studies. KRAS mutation status was proved to be a robust predictive biomarker for the efficacy of anti-epidermal growth factor receptor (anti-EGFR) therapies (4). It was reported that about 15-20% of CRC patients carried PIK3CA mutation (7), 80% of which was found in exon 9 and exon 20 (8). Previous studies indicated that patients with PIK3CA mutation could benefit from regular Aspirin treatment (9, 10), while the prognostic impact of PIK3CA mutation has far been controversial (11–15). 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

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Conclusion