The Characteristic Analysis Of Epidemiology?Molecular Typing And Pathological Typing Of Uygur Lung Cancer Patients

Objective: To analyze the clinical and pathological characteristics of Uyghur lung cancer patients in Xinjiang,find out the distribution characteristics and differences of lung cancer in Xinjiang,and further study the relationship among molecular subtyping,pathological type characteristics and prognosis of Uyghur patients with lung cancer.Methods:(1)The lung cancer patients of Uyghur nationality treated in Affiliated Cancer Hospital of Xinjiang Medical University were collected,and comparative analysis and follow-up visit were conducted to these patients for their clinical data like TNM stage,pathology,and driver gene.(2)Uyghur lung adenocarcinoma patients admitted to the Affiliated Cancer Hospital of Xinjiang Medical University were collected;Next-generation sequencing technology was used to detect 11 genes with clear relation to lung cancer among 106 Uyghur lung adenocarcinoma population,and thus,understand the specific gene mutation of Uyghur lung cancer patients,and analyze the relationship between gene mutation spectrum of Uyghur lung adenocarcinoma patients and their clinical and pathological characteristics.The relationship between molecular subtyping and co-stimulatory molecules B7-H3 of Uyghur lung adenocarcinoma patients was further analyzed.We detected the expression status of B7-H3 protein in lung adenocarcinoma tissues,and evaluated the relationship of B7-H3 expression and patients' prognosis.Then,we silenced its expression in A549 cells by transient siRNA transfection to ascertain the function of B7-H3 in lung adenocarcinoma cells.Western blot was used to detect the expression of epithelial-mesenchymal transition(EMT)related proteins.(3)The new lung adenocarcinoma classification method was used to re-classify 190 Uyghur patients with lung adenocarcinoma and determine the proportion of each histopathological subtype.The relationship between these results and the EGFR and ALK mutations was analyzed statistically to reveal the relationship between the pathologic subtypes and prognosis.Results:(1)The male/female ratio was 2.87: 1;Lung adenocarcinoma was dominating among the female and urban patients of Uyghur nationality,while squamous carcinoma and small cell lung cancer mostly occurred to the males/those with smoking history/rural patients;Small cell lung cancer patients had the lowest 3-year survival rate,and lung adenocarcinoma patients had the highest 3-year survival rate;23.8%(69/290)of these patients had EGFR gene mutation,and this was common to those not smoking,adenocarcinoma patients,and female patients;Pathological pattern and TNM stage were independent factors influencing the prognosis of NSCLC patients of Uyghur nationality.(2)Of the 106 Uyghur lung adenocarcinoma tissues tested,gene mutation was detected in 69 cases and the other 37 patients did not show any mutation;9 types of gene mutation were detected,including: 28 cases of KRAS mutation,27 cases of EGFR mutation,5 cases of ALK mutation,3 cases of ROS1 mutation,2 cases of BRAF mutation,1 cases of KIF5B-RET mutation,1 cases of NRAS mutation,1 cases of MET mutation and 1 case of PIK3 CA.The high expression of immune checkpoint molecule B7-H3 was significantly related to female,non-smoker,adenocarcinoma,poor prognosis and EGFR mutation;no mutation related to ALK?KRAS?PIK3CA?ERBB2(HER-2)?MET?NRAS?BRAF?DDR2?ROS1?RET gene mutation was observed.(3)The 5-year overall survival rate of Uygur patients with pathological type(AIS/MIA)were 100%,while the 5-year overall survival rate of patients with MP and SLD prime type was significantly lower than those of other subtypes.The EGFR/ALK in ACN has the highest mutation frequency,followed by PAP and LAP,however,there was no statistically significant difference(P>0.05)among the three;the mutation frequency of EGFR and ALK in tissues MP and SLD prime were relatively low.At the same time,we found that the mutation frequency of EGFR and ALK were relatively low in(AIS/MIA).Conclusions:(1)Lung cancer patients of Uyghur nationality had relevant characteristics in clinical features,pathological pattern,epidemiological distribution,and driver gene.Pathological pattern and TNM stage were independent factors influencing the prognosis of NSCLC patients of Uyghur nationality.(2)Through the detection of gene mutation in Uygur lung adenocarcinoma population,the frequency spectrum of genetic variation and its correlation with clinicopathological characteristics were determined.In this study,we found that B7-H3 over-expressed in Uyghur lung adenocarcinoma.It is correlated with lymph node metastasis and disease stage.The Cox regression analysis showed that B7-H3 might serve as an independent prognostic marker of lung adenocarcinoma.We also found that B7-H3 promoted proliferation,invasion and migration of A549 cell in vitro.B7-H3 also could promote EMT progression by regulating EMT-related molecules.(3)Pathological typing of Uygur lung adenocarcinoma is associated with prognosis.EGFR and ALK mutations are also associated with pathological typing of Uygur lung adenocarcinoma.