Clinical Characteristics And Related Analysis Of EGFR、ALK、ROS1 And PD-1/PD-L1 In Non-small Cell Lung Cancer

Background and purposeAccording to the global cancer statistics in 2020,lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer death in 2020,with an estimated 1.8 million deaths,followed by colorectal,liver,stomach,and female breast cancers.According to the Chinese cancer statistics released in 2015,lung cancer is the leading cause of cancer morbidity and mortality,and 85%lung cancer patients are diagnosed as non-small cell lung cancer(non-small cell lung cancer,NSCLC).The immune checkpoint inhibitors(ICIs)for programmed death-1(PD-1)and its ligand 1(PD-L1)are new advance in the treatment of advanced lung cancer,which have significantly increased the five-year survival rate of advanced lung cancer,and become first-line or second-line treatment options for patients without driver gene mutations in non-small cell lung cancer.The degree of malignancy and prognosis are associated with PD-1 expression in lung cancer,and PD-1 can be used as one indicator for assessing the prognosis in patients with non-small cell lung cancer.The studies have reported that the response rate of ICIs can be predicted by the expression level of PD-L1 in tumor tissue,and patients with high expression of PD-L1 are more likely to benefit from immunotherapy.National Comprehensive Cancer Network(NCCN)guidelines listed PD-L1 as a recommended routine test for NSCLC patients in 2018,choosing immunotherapy in combination with the expression state of PD-L1.Molecular targeted therapies for epidermal growth factor receptor(EGFR),anaplastic lymphoma kinase(ALK),ros proto-oncogene 1(ROS1)mutations have significantly improved the survival time and quality of patients with advanced non-small cell lung cancer.Previous studies have shown that patients with EGFR(epidermal growth factor receptor)mutations don’t have improvement in the survival rate after receiving ICIs,suggesting that EGFR mutations may affect the expression of PD-1/PD-L1,change tumor microenvironments,and affect the efficacy of ICIs.There are multiple identical signaling pathways between PD-1/PD-L1 and driving gene mutations that jointly induce the occurrence and development of neoplasm,and the association between them is not clear.And there is no agreement on the conflict between targeted therapy and ICIs.Therefore,the relationship between EGFR,ALK,ROS1 and PD1/PD-L1 and clinical pathological characteristics were analyzed,and providing preliminary theoretical basis for immune and targeted treatment.MethodsThis study collected patients with non-small cell lung cancer admitted to Zhengzhou University First Affiliated Hospital from January 2019 to December 2019,of which EGFR,ALK,ROS1,PD-L1 were detected from 499 patients and PD-1 was detected from 372 patients,and collected clinical data of selected persons by searching electronic medical records system.PD-1/PD-L1 expression was obtained by immunohistochemistry from the pathology department of the hospital,and PD-L1 expression was evaluated according to the tumor proportion score(TPS):TPS<1%was PD-L1 expression negative,TPS>1%was PD-L1 expression positive,1%≤TPS<50%was PD-L1 low expression and TPS>50%was PD-L1 high expression.The EGFR,ALK and ROS1 genes were detected by next-generation sequencing(NGS).The clinical characteristics and the correlation between EGFR,ALK,ROS1 and PD-1/PD-L1 expression were analyzed by SPSS 25.0 statistical software.Results1.EGFR,ALK and ROS1 gene were tested from 499 NSCLC patients,among which 246(49.3%)were EGFR mutations,32(6.4%)were ALK fusion positive,10(2.0%)were ROS1 positive.499 NSCLC patients were tested for PD-L1,of which 33(6.6%)were high-expression and 101(20.2%)were low-expression;372 NSCLC patients were tested for PD-1,of which 33(8.9%)were positive.2.EGFR in NSCLC patients was correlated with sex,smoking history,pathological type,brain metastasis,bone metastasis,lymph node metastasis and tumor longest length(P<0.05),but there were no differences in age,liver metastasis,adrenal metastasis,lateral pulmonary metastasis and TNM stages(P>0.05).ALK in NSCLC patients was correlated with age,smoking history,and lymph node metastasis(P<0.05),but there were no differences in sex,pathological type,liver metastasis,brain metastasis,bone metastasis,adrenal metastasis,lateral pulmonary metastasis,tumor longest length,and TNM stages(P>0.05).ROS1 in NSCLC patients was not correlated with sex,age,smoking history,pathological type,tumor longest length,lymph node metastasis,bone metastasis,liver metastasis,brain metastasis,adrenal metastasis,lateral pulmonary metastasis,TNM stages(P>0.05).3.PD-1 showed higher positive rate in squamous cell carcinoma,adrenal metastasis and tumor longest diameter 5-7cm(P<0.05),but there were no differences in age,sex,smoking history,brain metastasis,bone metastasis,liver metastasis,lateral pulmonary metastasis,lymph node metastasis and TNM stages(P>0.05).The positive rate of PD-L1 was significant higher in patients of male,smoking history,non-adenocarcinoma,non-brainless metastasis and lymph node metastasis(P<0.05),but there were no statistically significant differences in age,bone metastasis,liver metastasis,adrenal metastasis,lateral pulmonary metastasis,tumor longest length and TNM stages(P>0.05).4.PD-1 positive accounted for 8.4%(15/178)in the EGFR mutation group,and accounted for 9.3%(18/194)in the wild group of EGFR,and statistical analysis showed that PD-1 expression in NSCLC was not associated with EGFR mutation(r=0.015,P=0.773).PD-L1 positive was 23.2%(57/246)in the EGFR gene mutation group,PD-L1 positive in the wild group of the EGFR gene was 30.4%(77/253),and statistical analysis showed that PD-L1 expression in NSCLC was not associated with EGFR gene mutation(r=0.082,P=0.067).5.PD-1 in NSCLC is associated with ALK gene fusion(r=0.184,P=0.000).PD-L1 positive rate was 15.6%(5/32)in ALK gene fusion,PD-L1 positive rate in ALK gene fusion negative was 27.6%(129/467),but statistical analysis showed that PD-L1 protein expression in NSCLC was not associated with ALK gene(r=0.066,P=0.138).6.The PD-1 expression was divided into positive and negative groups,ROS1 was associated with PD-1 expression(r=0.163,P=0.001).The PD-L1 expression was divided into positive and negative groups,and the results showed that ROS1 and PD-L1 were not associated(r=0.022,P=0.621).Conclusions1.PD-1 expression showed higher positive rate in NSCLC patients with squamous cell carcinoma,adrenal metastasis and tumors with a maximum diameter of 5-7cm.PD-L1 showed higher positive and high expression rate in NSCLC patients with men,smoking,non-adenocarcinoma,non-brain metastasis,and lymph node metastasis.2.EGFR had higher positive rate in NSCLC patients with female,non-smoking history,adenocarcinoma,brain metastasis,bone metastasis,non-lymph node metastasis.ALK had higher positive rate in NSCLC patients with younger,non-smoking,lymph node metastasis.ROS1 in NSCLC patients was not correlated with sex,age,smoking history,pathological type,tumor longest length,lymph node metastasis,bone metastasis,liver metastasis,brain metastasis,adrenal metastasis,lateral pulmonary metastasis,TNM stages.3.EGFR was not associated with PD-1/PD-L1 expression.ALK was associated with PD-1 expression,and not associated with PD-L1 expression.ROS1 fusion was associated with PD-1 expression,and not associated with PDL1 expression.