Correlation Analysis And Significance Of PD-L1 And CTLA-4 Expression And KRAS Gene Mutation In Microsatellite Stable Colorectal Cancer

Objective:To investigate the correlation and clinical significance of KRAS gene mutations with CTLA-4 and PD-L1 expression in microsatellite stable(MSS)colorectal cancer(CRC).The aim is to achieve precise staging and personalized treatment for MSS-type CRC.Methods:1.Collect and organize the clinical case data and paraffin specimens of 330 patients diagnosed with MSS-type CRC at the Shanxi Cancer Hospital from June 2020 to June 2021.2.Immunohistochemistry(IHC)was used to detect the protein expression of PD-L1 and CTLA-4 in the 330 CRC patients.3.The amplification refractory mutation system-quantitative real-time PCR(ARMSq PCR)technique was used to detect KRAS gene mutations,and analysis was performed based on clinical-pathological data.4.SPSS 25.0 statistical software was used to statistically analyze the expression of PD-L1 and CTLA-4 proteins and KRAS gene mutations in MSS-type CRC,and compared with the various clinical and pathological characteristics of patients.Results:1.IHC results: PD-L1 showed membranous positivity,with a positivity rate of 38.8%(128/330)in MSS type CRC,while CTLA-4 showed positivity in both membranous and cytoplasmic staining,with a positivity rate of 32.1%(106/330)in MSS type CRC.2.PCR results: The mutation rate of KRAS gene was 42.7%(141/330),with the most frequent mutation found in codon 12,exon 2,with a mutation rate of 35.5%(117/330).Among the mutations in codon 12,p.G12 D was the most common,with a mutation rate of18.8%(62/330),followed by p.G12 V in codon 12 with a mutation rate of 15.2%(50/330).3.Association between PD-L1,CTLA-4 positivity,KRAS mutation and clinical pathological characteristics: PD-L1 and CTLA-4 expression were associated with pathological staging(P < 0.05).No statistical significance was found in age,lesion location,tumor differentiation degree,lymph node metastasis,tumor diameter,and distant metastasis(P > 0.05).When PD-L1 and CTLA-4 were co-expressed,they were associated with tumor differentiation degree and pathological staging(P < 0.05).No statistical significance was found in age,lesion location,lymph node metastasis,tumor diameter,and distant metastasis(P > 0.05).KRAS gene mutation was associated with gender,pathological staging,and distant metastasis(P < 0.05).No statistical significance was found in age,lesion location,lymph node metastasis,tumor diameter,and differentiation degree(P > 0.05).4.Correlation between PD-L1 and CTLA-4 protein expression: The expression of PDL1 and CTLA-4 showed a positive correlation(r=0.771,P<0.05).5.Correlation between KRAS gene mutation and PD-L1,CTLA-4 protein expression:KRAS gene mutation was positively correlated with the expression of PD-L1(r=0.708,P<0.05)and CTLA-4(r=0.587,P<0.05).Conclusion:The protein expression of PD-L1 and CTLA-4 is positively correlated with pathological staging,indicating that high expression of both proteins predicts poor prognosis.The positive correlation between PD-L1 and CTLA-4 protein expression suggests a potential interaction mechanism between the two.The positive correlation between KRAS gene mutations and PD-L1 and CTLA-4 protein expression suggests that a combination of existing biomarkers can be used to screen potential treatment beneficiaries,providing a new direction for the treatment of MSS-type CRC and promoting the development of more precise CRC treatment.