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

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

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.595675

DOI=10.3389/fonc.2021.595675

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p><italic>PIK3CA</italic> 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 <italic>PIK3CA</italic> in Chinese CRC cohort.</p></sec><sec><title>Methods</title><p>The <italic>PIK3CA</italic> 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.</p></sec><sec><title>Results</title><p>Fifty-eight types of mutations in 13.4% (771/5733) of the patients were detected. From 2014 to 2018, the mutation rate of <italic>PIK3CA</italic> 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; <italic>p</italic>-value = 0.012). At stage III, <italic>PIK3CA</italic> mutated patients were more likely to relapse (multivariate Logistic regression analysis, exon 9: OR = 2.54, 95% CI = 1.34-4.73, <italic>p</italic> = 0.003; exon 20: OR = 3.89, 95% CI = 1.66-9.10, <italic>p</italic> = 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 <italic>PIK3CA</italic> 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, <italic>p</italic>-value = 0.513).</p></sec><sec><title>Conclusions</title><p>We found that <italic>PIK3CA</italic> 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 <italic>PIK3CA</italic> exon 9 mutations are not negative predictors of cetuximab treatment in <italic>KRAS</italic>, <italic>NRAS</italic>, and <italic>BRAF</italic> wild-type mCRC patients.</p></sec>