| Objective: 1.To analyze the mutations and co-mutations of the PIK3 CA,KRAS,and ALK genes in patients with non-small cell lung cancer(NSCLC)in the Jiaodong Peninsula;To explore the correlation between gene mutation and clinicopathological features and prognosis.2.To analyze the relationships between differentiation,clinicopathological features,and prognosis of lung adenocarcinoma.Methods: 1.2167 NSCLC specimens,diagnosed in the pathology department of the Affiliated Hospital of Qingdao University from October 2017 to May 2020,were collected.The clinical data were sorted out,and the sections were reviewed to evaluate the differentiation of lung adenocarcinoma according to the 2021 WHO classification of thoracic tumors.2.The overall survival(OS)of 1658 patients with NSCLC was obtained through telephone follow-up for 11 to 41 months with a median of 18 months.3.Mutations of 10 driving genes,including EGFR,KRAS,BRAF,PIK3 CA,ALK,ROS1,HER2,MET,RET,and NRAS were detected by next-generation sequencing(NGS)in 2167 NSCLC samples.4.The statistical software prism 8.0 and SPSS 26.0 were used for statistical analysis.The correlation between mutations of KRAS,PIK3 CA,and ALK and clinicopathological features was tested by chi-squared test,Yates’ s correction for continuity,or Fisher exact test.Kaplan Meier survival analysis was used to compare the relationship between different mutation characteristics together with the degree of differentiation and overall survival.Results: 1.Among 2167 patients with non-small cell lung cancer,1197 were women(53.1%)and 970 were men(46.9%)with an average age of 60.4 years old.There were 1566 patients in AJCC clinical stage I,171 patients in stage II,131 patients in stage III,and 195 patients in stage IV.The follow-up data of 1658 cases were collected from whom 1497 survived while 161 died with a follow-up time of 11-41 months.There were 1984 cases of adenocarcinoma,133 cases of squamous cell cancer,20 cases of adenosquamous carcinoma,3 cases of large cell carcinoma,4 cases of mucoepidermoid carcinoma,1 case of carcinosarcoma,and 30 cases of NSCLC non-specific type in biopsy specimens.2.PIK3 CA single gene mutation was more likely to occur in patients with smoking history(P < 0.05),men(P < 0.01),and squamous cell carcinoma(P < 0.001);in this case,pleural invasion(P < 0.05)and lymph node metastasis(P < 0.001)were more likely to occur.The tumor with the co-mutation of PIK3 CA and EGFR had a higher proportion of the solid type and the micropapillary type,and was prone to lymph node metastasis.PIK3 CA gene mutation was associated with a poor prognosis(P < 0.001).3.KRAS gene mutation frequency was higher in patients with smoking history(P <0.001),male(P < 0.001),advanced(stage III / IV)(P < 0.01)and adenocarcinoma(P <0.001),and it was significantly correlated with solid(P < 0.001)and mucinous adenocarcinoma(P < 0.001).Tumors with KRAS gene mutation were prone to distant metastasis(P < 0.001).KRAS gene mutation was significantly correlated with poor prognosis(P < 0.001).4.ALK gene rearrangement is common in adenocarcinoma patients(P < 0.05)younger than 60 years old(P < 0.05),which is enriched in solid adenocarcinoma with intracellular mucus and indicates a poor prognosis.5.Among 914 cases of surgical-resected non-mucinous adenocarcinoma,327 cases were poorly differentiated,423 cases were moderately differentiated and 164 cases were well-differentiated.In addition,the correlation analysis between mutations and clinical characteristics showed that KRAS gene mutation was significantly related to the degree of tumor differentiation(P < 0.001),the PIK3 CA,KRAS,and ALK genes mutation frequency were higher in the low-differentiation group than in the high and medium differentiation groups.Conclusion: 1.Epidemiologically,PIK3 CA mutation and KRAS mutation are common in male patients with a smoking history,while ALK rearrangement is common in non-smoking women patients.Histologically,PIK3 CA mutation is common in squamous cell carcinoma;KRAS mutation and ALK rearrangement are common in adenocarcinoma;Meanwhile,ALK mutation is associated with solid subtypes,intracellular mucus,and signet ring cell characteristic.2.PIK3 CA gene is a common co-mutation driver gene,while KRAS and ALK genes can co-mutate with other driver genes.3.The prognosis of patients with PIK3 CA and KRAS mutations was poor,and the OS difference in ALK-rearrangement patients was not statistically significant.4.KRAS gene is related to the degree of tumor differentiation,PIK3 CA,KRAS mutations,and ALK rearrangement tend to occur in patients with low-differentiated adenocarcinoma. |
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