Correlation of PIK3CA mutation with programmed death ligand-1 (PD-L1) expression and their clinicopathological significance in colorectal cancer

Abstract

Background: The prognostic significance of PIK3CA mutations in colorectal cancer (CRC) remains controversial. Recently, an association between programmed death ligand-1 (PD-L1) and PIK3CA mutations has been reported. The study presented here was conducted to investigate the effect of PIK3CA mutations on the prognosis of CRC patients and the association between PIK3CA mutations and PD-L1.Methods: PIK3CA mutations were analyzed by targeted next-generation sequencing using formalinfixed paraffin-embedded specimens from 224 primary CRC patients. PD-L1 expression was evaluated by immunohistochemical staining.Results: PIK3CA mutations and PD-L1 expression were detected in 21.4% and 10.3% of CRC patients, respectively. PIK3CA mutations were significantly correlated with right-side colon cancer (P=0.011) and were correlated inversely with lymph node metastasis (P=0.026), distant metastasis (P=0.047), and high TNM stage (P=0.036). In univariate analysis, PIK3CA mutations were correlated with longer relapse-free survival in CRC patients. PD-L1 expression was correlated significantly with PIK3CA mutations (P<0.001).Conclusions: PIK3CA mutations were associated with favorable prognostic factors, longer relapse-free survival, and expression of PD-L1. Further investigation is needed to identify whether PIK3CA mutations are a good prognostic factor. Additionally, further studies are needed to understand the mechanisms behind the correlation between PIK3CA mutations and PD-L1 expression.

High Probability of Lynch Syndrome among colorectal cancer patients in Indonesia is associated with higher occurrence of KRAS and PIK3CA mutations

“…However, in this study, we found a subset of lower numbers of TILs in PIK3CA-mutated cases, suggesting an immuneinvading mechanism at play. Interestingly, PD-L1 expression was correlated with PIK3CA mutations, suggesting that cancers with PIK3CA mutations and PD-L1 expression are immunotherapy candidates [64]. Inhibition of the PI3K-AKT pathway may improve effector T cell infiltration in PI3K-altered CRC.…”

“…Interestingly, PD-L1 expression was correlated with PIK3CA mutations, suggesting that cancers with PIK3CA mutations and PD-L1 expression are immunotherapy candidates [64]. Inhibition of the PI3K-AKT pathway may improve effector T cell infiltration in PI3K-altered CRC.…”

Molecular Subtypes, microRNAs and Immunotherapy Response in Metastatic Colorectal Cancer

“…Higher levels of PD-L1 expression in tumor tissues theoretically correlate with an improved response to ICI treatment [ 85 ]. Over 50% of colon cancer patients [ 86 ] exhibit positive PD-L1 expression (10% cut-off). PD-L1 expression alone is insufficient for accurately predicting the response to immunotherapy in colon cancer.…”

“…In the second- or third-line setting, there are multiple phase I/II clinical trials reporting on the efficacy of PD-L1/PD-1 inhibitors: pembrolizumab, dostarlimab, nivolumab, and avelumab, with similar results, with an ORR between 30–38% [ 86 , 96 , 105 , 106 ]. The phase II Checkmate 142 trial tested the PD-1 and CTLA4 dual blockade in pre-treated patients, reporting a ORR of 55%, mPFS not reached [ 107 ].…”

Predictive biomarkers of colon cancer immunotherapy: Present and future

“…PD-L1 expression is postulated as a predictive biomarker of immunotherapy response in some solid tumors, such as NSCLC, melanoma, and renal cell cancer (116)(117)(118). Positive PD-L1 expression (with a cut-off value of 10%) is reported in more than half of colon cancer patients (119,120). Although a high PD-L1 expression is associated with a better prognosis in colon cancer patients (20,(121)(122)(123).…”