| BackgroundLung cancer is the leading malignant tumor that causes global cancer death.Most patients are diagnosed late,and the overall 5-year survival rate is extremely low.With the discovery of lung cancer mutated gene,more than 60% driver gene of non-small cell lung cancer have been confirmed,and the corresponding targeted drugs have also been appear on the market.Compared with traditional chemotherapy,targeted therapy is highly effective and low toxicity.It has been confirmed that human epidermal growth factor receptor 2(HER2)mutantion leads to the progression of non-small cell lung cancer,and the corresponding targeted drugs have entered clinical trials and achieved good therapeutic effect.However,the incidence of HER2 mutations is relatively low,and the rate of driving gene in patients with non-small cell lung cancer in different countries and regions are also different.In China,there is still a lack of large sample analysis of clinical pathological feature and prognostic analysis of non-small cell lung cancer patients with HER2 mutantion.Therefore,we need in-depth study to understand the clinicopathological feature and prognostic analysis of non-small cell lung cancer patients with HER2 mutantion in China,so can we lay a foundation for the search for effective biomarkers for disease prognosis,and to provide more parameters for clinical trials of HER2 gene targeted therapy in later period.ObjectiveTo investigate the clinicopathological feature and survival time of non-small cell lung cancer patients with HER2 mutantaion,and the effect of HER2 mutation on first-line chemotherapy prognosis in patients with advanced non-small cell lung cancer..MethodsThis study was retrospectively analyzed and selected from 482 patients who were diagnosed as non-small cell lung cancer by histopathology at the First Affiliated Hospital of Zhengzhou University from 2013.01-2018.01.These patients have never received chemotherapy and/or immunotherapy in any way prior to histopathological diagnosis.Collecting the genetic test results of paraffin samples determined by the next generation sequencing method.Clinical data including gender,age,family tumor history,smoking history,histopathological type,whether lymph node metastasis,bone metastasis,brain metastasis,EGFR mutation and ALK mutation were obtained by using the electronic medical record system.Outpatient or telephone follow-up was used for the collection of patients’ survival time,and the deadline was September 1,2018.The data was statistically processed and analyzed by SPSS 17.0.The test level was α=0.05,P<0.05 was considered statistically significant.Results1.Clinicopathological features of non-small cell lung cancer patients with HER2 mutation1.1 HER2 gene mutation: In this study,482 patients with non-small cell lung cancer were selected as subjects,and 28 patients were positive for HER2 mutation.The mutation rate was 5.81%(28/482),of which 22 were 20 exons insertion mutation(78.57%),and 2 patients were 20 exon mutation combined with HER2 gene amplification,3 patients with 19 exon deletion mutation(10.71%),and 1 patient with 22 exon missense mutation(3.57%),1 patient had a 27-exon missense mutation(3.57%),and 1 patient had a 16-exon missense mutation(3.57%).1.2 Age of onset,gender: The average age of patients with HER2 gene mutation was(55.25±10.35)years old(31-74 years old),the average age of negative mutation patients was(60.31±10.26)years old(26-85 years old).The mean age of small cell lung cancer patients with HER2 mutation was younger than that of HER2-negative patients,and the difference was statistically significant(P=0.012).There was no significant difference in the rate of HER2 gene mutation between male and female patients(P=0.092).1.3 History of smoking,family history of cancer: There was no significant difference between HER2 gene mutation and smoking history(P=0.185).In the family history of tumors,it was found that patients with family history of tumor had high mutation rate of HER2 gene than patients without family history of tumors(13.95% vs.4.04%),the difference was statistically significant(P < 0.001).1.4 Histopathological typing: The HER2 gene mutation was not associated with histopathological typing of tumor cells(P=0.832).1.5 Tumor metastasis and clinical stage: The mutation rate of HER2 gene in patients with lymph node metastasis was significantly higher than that in patients without lymph node metastasis(7.39% vs 1.54%)(P=0.015).The mutation rate of HER2 gene in patients with bone metastasis was higher than that in patients without bone metastasis(10.30% vs 3.47%)(P=0.002);The detection rate of HER2 gene mutation in patients with brain metastasis was higher than patients without brain metastasis(10.75% vs 4.63)(P=0.023);The HER2 gene mutation rate in patients with clinical stage III-IV was significantly higher than that in patients with clinical stageI-II(7.37% vs 0.00%)(P=0.005).1.6 Concomitant gene status in patients with HER2 mutation:The detection rate of HER2 mutation in EGFR-negative patients was significantly higher than that in EGFR-positive patients(10.73% vs 0.00%)(P<0.001);There was no significant difference in HER2 gene mutation rate between patients with positive ALK gene mutation and patients without ALK gene mutation(P=0.217).2.Survival time of non-small cell lung cancer patients with HER2 mutantion: All the 28 patients with HER2 mutation occurred in non-small cell lung cancer patients with stage III-IV,with a median overall survival of 13.0 months(95% CI:11.534-14.466months);Further grouping according to pathological type,25 patients with lung adenocarcinoma patients with median overall survival of 13.0 months(95%CI:11.368-14.632months),3 patients with lung squamous cell carcinoma with median overall survival of 9.0 months(95%CI:2.599-15.401months).The median overall survival of lung squamous cell carcinoma patients with HER2 mutantion was shorter than that of patients with lung adenocarcinoma,but the difference was not statistically significant(P=0.079).3.The effect of HER2 mutation on progression-free survival in patients with advanced lung adenocarcinoma and lung squamous cell carcinoma using first-line chemotherapy: In lung adenocarcinoma patients with stage III-IV using first-line chemotherapy,median progression free survival in patients with HER2 mutation was 4.0 months(95% CI:3.581-4.419months),and the median progression-free survival of patients without HER2 mutation was 5.0 months(95% CI:4.705-5.295months),The progression-free survival of patients with HER2 mutation was shorter than that of patients without HER2 mutation,and the difference was statistically significant(P=0.003).In lung squamous cell carcinoma patients with stage III-IV who received first-line chemotherapy,the median progression-free survival of patients with HER2 mutation was 4.0 months(95%CI:0.799-7.201months),median progression free survival in patients without HER2 mutation was 6.0 months(95% CI:5.668-6.332 months).Among patients with advanced lung squamous cell carcinoma treated with first-line chemotherapy,the median progression-free survival of patients with HER2 mutation was shorter than that of patients without HER2 mutation,but the difference was not statistically significant(P=0.182).Conclusions1.HER2 mutation is often an insertion mutation of exon 20,which mostly occurs in patients with non-small cell lung cancer with a family history of tumor,lymph node metastasis,brain metastasis,bone metastasis,and clinical stage III-IV.HER2 mutation and EGFR mutation are mutually exclusive.2.The median progression free survival of HER2 mutation patients with advanced lung adenocarcinoma using first-line chemotherapy regimen is shorter than that of HER2 negative patients,HER2 mutation may indicate poor prognosis. |
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