Clinicopathologic Features And Molecular Biology Of Pulmonary Sarcomatoid Carcinoma

Objective:This study analyzed the clinicopathologic and immunohistochemical characteristics of pulmonary sarcomatoid carcinoma(PSC),to explore the influencing factors of Progress-free survival(PFS)and Overall survival(OS)in patients with PSC.Second generation sequencing was performed on some patients with PSC to analyze the gene mutations of patients with PSC,and to search for key genes that may be related to the occurrence and development of PSC and potential therapeutic targets.Method:A total of 40 patients diagnosed with PSC after surgery in China-Japan Friendship Hospital from January 2016 to October 2022 were included in our study.The clinicopathologic data of all patients were collected,and the postoperative specimens were stained with HE and immunohistochemical staining to analyze the clinicopathologic features,and immunotyping was performed according to the expression of PD-L1 and infiltration of CD8+T cells.The clinicopathological features,treatment methods,immunotyping and prognosis of PSC patients were analyzed.SPSS26.0 was used for statistical processing,Kaplan-meier method was used for survival analysis,Log-rank test was used to analyze the significant differences in survival curves,and Cox regression model was used for multivariate analysis.P<0.1 was considered statistically significant.From 40 patients with PSC in the whole group,24 patients who underwent surgical treatment between March 2018 and January 2022 were selected for second-generation sequencing to screen the mutated genes that may be related to PSC.P<0.05 was considered statistically significant.Results:The results showed that TNM(Tumor node metastasis and classification)stage(P=0.028),vascular thrombi(P=0.006),lymph node metastasis(P=0.013),PD-L1(Programmed cell death 1 ligand 1)expression(P=0.04)and immunophenotype 2(P=0.005)were correlated with PFS in PSC patients.Multivariate analysis suggested that PD-L1 expression(HR 3.732,95%CI 0.870-16.012,P=0.076)was an independent factor influencing PFS in patients with PSC.TNM stage(P=0.014),vascular thrombus(P=0.012),lymph node metastasis(P=0.008),PD-L1 expression(P=0.034),immunophenotype 1(P=0.094),immunophenotype 2(P=0.005)and treatment method(P=0.039)were correlated with OS in PSC patients.Multivariate analysis suggested that TNM stage(HR 23.878,95%CI 0.740-106.742,P=0.014)and treatment style(HR 0.049,95%CI 0.008-0.309,P=0.001)were independent influencing factors for OS in PSC patients.50%(20/40)of PSC patients were identified as PD-L1 positive,and 17.5%(7/40)of patients had a positive Tumor cell Proportion Score(TPS)greater than 40%.The resul ts of second-generation sequencing showed significant heterogeneity in the number,type and distribution of driving mutations between PSC and Non-Small Cell Lung Cancer(NSCLC).PSC is more prone to TP53,CDKN2A,CREBBP,MCL1,MLL2,MLL,FANCF,FAT1,MUTYH,PARK2,BRCA1,BCL2L1 and ARID1A mutations.KEGG target enrichment analysis indicated that P13K-Akt signaling pathway,P53 signaling pathway,JAK-STAT signaling pathway and Fanconi anemia signaling pathway in tumor were the key signaling pathways causing the above differential genes.Conclusion:PD-L1 expression is an independent factor affecting PFS in patients with PSC.TNM staging and treatment method were independent factors influencing OS in PSC patients.PSC has a high positive rate of PD-L1,which is expected to guide clinical immunotherapy based on immune typing.PSC is more prone to TP53 and other driver mutations.P13K-Akt signaling pathway and JAK-STAT signaling pathway play important roles in the development and transformation of PSC.