Clinical Molecular Pathological Features And Prognosis Analysis Of Advanced Non-Small Cell Lung Cancer With KRAS Mutation

Objective:The prognosis for non-small cell lung cancer(NSCLC),a frequent aggressive tumor,is dismal.The mutant murine sarcoma virus oncogene(KRAS)is a significant contributor in the pathogenesis and development of NSCLC.In this study,38 cases of late stage NSCLC with KRAS mutation were identified by second-generation sequencing technology,and the characteristics and co-mutation of common mutation subtypes of KRAS gene were discussed,and the relationship between common gene mutation subtypes and clinicopathological characteristics and prognosis was further analyzed.Methods:(1)The results of gene tests from second-generation sequencing(NGS)in 360 patients with advanced NSCLC were reviewed retrospectively.The KRAS gene mutation was the driver gene in 38 of them,and the KRAS mutation subtypes and co-mutations were statistically analyzed.(2)The relationship between KRAS gene common mutation sites and clinicopathologic features such as gender,age,pathological type,stage,tumor primary site,tumor metastasis site,therapeutic efficacy,survival,and so on was investigated.(3)The association between common KRAS gene mutation sites and prognosis was investigated,including progression-free survival(PFS),overall survival(OS),and so on.Results:1.General characteristics,subtype distribution,and co-mutation of patients with KRAS mutation: 38 patients with KRAS mutation were identified among 360 NSCLC cases tested by NGS,representing a mutation rate of 10.56%.There were 22 men(57.89% of the total)and 16 women(42.11%).The average age was 64 years old(37-82 years old).Pathological types: 33 adenocarcinomas(86.84%),2 squamous cell carcinomas(5.26%),and 3 other types(7.90%).Clinical stage Ⅲ(ⅢB and ⅢC): 13cases(34.21%),clinical stage IV: 25 cases(65.79%).Subtypes of KRAS mutations:KRAS G12 C had the highest mutation rate,accounting for 28.95%(11/38).KRAS G12V: 26.32%(10/38),KRAS G12D: approximately 18.42%(7/38).Co-mutation of the KRAS gene with the TP53 gene: 14 cases(36.84%)were co-mutated,accounting for the highest proportion.The STK11 gene had 8 co-mutations(21.05%),and other co-mutations included ERBB2 and LRP1 B.2.The association between KRAS mutation subtypes and clinicopathologic features:KRAS gene mutation had no statistical significance in gender,age,smoking history,or family tumor history compared to non-KRAS mutation NSCLC patients(P>0.05),but did have statistical significance in pathological type(P<0.05).KRAS mutations were more common in lung adenocarcinoma.KRAS G12 C,G12D,and G12 V gene mutations had no statistical significance in gender,age,smoking history,family history,or pathological type(P>0.05).3.Survival prognosis analysis: Of the 38 patients in this study,34 received treatment,with three dropping out during treatment.The median progression-free survival was3.5 months(95% CI: 2.5-4.5 m),with a 6-month progression-free survival of 29.41%.The 1-year survival rate was 56.73%,with a median overall survival of 12.5m(95%CI: 11.2-13.8 m).The 2-year survival rate was 28.5%.4.There was no statistically significant difference in prognosis between KRAS G12 mutation and other KRAS mutations(P=0.208),but there was a difference in survival prognosis between KRAS G12 C,KRAS G12 D,KRAS G12 V,and KRAS Others mutation sites(P=0.007).The prognosis was the worst for the KRAS G12 C mutant subtype.There was no statistical difference in total survival between KRAS/TP53co-mutated and non-KRAS/TP53 co-mutated patients(P=0.733),according to the group of KRAS co-mutated genes.There was no significant difference in overall survival between patients with and without KRAS/STK11 comutation(P=0.892).Conclusion:1.The mutation rate of the KRAS gene in advanced NSCLC was 10.56% in this study.KRAS G12 C,KRAS G12 V,and KRAS G12 D were the subtypes with the highest mutation rate.KRAS mutation is most common in lung adenocarcinoma patients,and there is no significant difference in clinicopathologic characteristics between mutation subtypes.2.In this study,the most common co-mutation types in advanced NSCLC with KRAS mutation were TP53 and STK11,with the KRAS/TP53 co-mutation rate accounting for 36.84%.3.In this study,the G12 C mutant subtype in advanced NSCLC with KRAS mutation had a poorer prognosis than other KRAS mutant subtypes.