Syndrome Type Of TCM Was Asscociated With The Molecular Pathogenetic Characteristics In Patients With Stage ⅢB/Ⅳ NSCLC

ObjectiveThe purpose of this study was to investigate the distribution of TCM Syndrome differentiation and molecular pathogenetic characteristics in patients with Non-small Cell Lung Cancer at IIIB/IV stage.For further study,providing a scientific basis for the combination of targeted therapy and TCM syndrome differentiation.MethodsWe prospectively studied 50 patients who are newly diagnosed with NSCLC without prior anticancer therapy or those were recurrence without any anticancer therapy.The symptoms and signs which can help for the TCM syndrome type diagnosis were recorded by questionnaire,and the Gene status and abundance were also tested by Next Generation Sequencing.According to five TCM syndromes of NSCLC in Clinical Practice Guidelines of Chinese Medicine in Oncology and patients ’ symptoms and signs,the TCM were diagnosed respectively at least 2 TCM experts of our hospital to decide the TCM syndrome type.Then we build database by Epidata3.1 and analyzed the relationship between the TCM syndrome type and molecular pathogenetic characteristics in NSCLC patients by SPSS.17.Results1.From May 2017 to January 2018,50 patients were enrolled in our study,and all of then were tested for NGS.50 patients were classified by TCM syndrome differentiation,including 33 cases of Qi deficiency syndrome,15 cases of yin deficiency syndrome,28 cases of phlegm-dampness syndrome and 5 cases of blood stasis syndrome.Toxic-heat syndrome in 4 cases.2.Baseline tissue / pleural fluid samples were detected in 56 genes,those genes were detected in 198 variants,including 47 CNV,6 rearrangements,115 point mutations,30 insertion or deletion mutations;49 genes,156 mutations,including 24 CNV,4 rearrangements,99 point mutations,29 an insertion or deletion mutation were detected in the plasma samples.No correlation was found between the other syndromes and molecular pathological typing,and consideration was related to insufficient sample size.3.The relationship between gene spectrum of NSCLC patients and TCM syndromes: the detection rate of ALK gene mutation in patients with yin-deficiency syndrome was higher than that in patients without Yin-deficiency syndrome.But the difference was not statistically significant(P=0.058).A total of 3 cases of ALK fusion and 1 case of p.Q1070 H point mutation were detected in 11 patients with Yin-deficiency syndrome.p.Q1070 H point mutation was close to that of ALK kinase.ALK fusion was detected in 2cases in 33 patients without yin deficiency syndrome.The detection rate of Erb B signal pathway mutation in patients without yin deficiency syndrome was higher than that patients without yin deficiency syndrome.But the difference was not statistically significant(P=0.074).There is a higher trend of max AF in plasma of patients with heat toxin syndrome.But the difference was not statistically significant(P=0.086).The detection rate of Focal adhesion(P=0.013)and HIF-1 signal pathway(P=0.046)was significantly higher in patients without Toxin-heat syndrome.The detection rate of human epidermal growth factor(EGFR)gene was the highest among the two signaling pathway genes.4.Correlation between molecular pathological characteristics and metastatic lesion:The abundance of EGFR mutation in patients with liver metastasis was significantly higher than that in patients with liver metastasis.The difference was statistically significant(P=0.02).The mutation abundance of EGFR was higher in patients with bone metastasis.The difference was not statistically significant(P=0.069).The detection rate of POM121L12 in patients with brain metastasis was significantly higher.The difference was statistically significant(P=0.011).5.Correlation between molecular pathological characteristics and primary site:The detection rate of FGFR1 was higher in the primary site of the central NSCLC.The difference was statistically significant(P=0.007).A total of 7cases of FGFR1 ampampsis were detected in 29 case patients with central type.Only 1 case of FGFR1 amp was detected in 21 case patients withprimary peripheral type.6.Correlation between molecular pathological characteristics and general clinical features:Correlation between molecular pathological classification and general clinical Patients with smoking or stage of IIIB have more CDKN2 A mutations.The difference was statistically significant(smoking(P=0.017),IIIB stage(P=0.016)).The detection rate of PTEN(P=0.013)and EGFR(P=0.042)and KRAS(P=0.082)in stage IV patients was higher and all mutations in tissues was significantly lower that in patients with stage IV.Plasma max AF was significantly decreased in women(P=0.016)without smoking(P=0.016).Tissues max AF was significantly decreased in women(P=0.016).EGFR AF was significantly higher in women(P=0.008)without smoking(P=0.001).The detection rate of TP53 was significantly lower in women(P=0.005)without smoking(P=0.024).conclution1.TCM syndrome differentiation of stage Ⅲ B / Ⅳ non-small cell lung cancer has Qi deficiency syndrome,phlegm dampness syndrome,Yin deficiency syndrome,blood stasis syndrome and heat toxin syndrome.The main characteristics of the disease are middle-aged and aged men and smokers.2.In stage Ⅲ B / Ⅳ non-small cell lung cancer(NSCLC),the mutation of ALK gene was more common in the patients with Yin deficiency syndrome.The possibility of Erb B signal pathway mutation in patients without yin deficiency syndrome,and EGFR gene mutation was the most common mutation.The mutation abundance of PLA max AF in patients with heat toxin syndrome had a higher tendency,which suggests that heat toxin syndrome was prone to blood metastasis.The detection rate of Focal adhesion signal pathway and HIF-1signal pathway was significantly higher in patients without Toxin-heat syndrome.It suggest that heat toxin syndrome was prone to gene mutation,but not heat toxin syndrome to rare signal pathway gene mutation.3.EGFR mutations in plasma of patients with stage Ⅲ B / Ⅳ non-small cell lung cancer with liver metastasis and bone metastasis were significantly higher,suggesting that the patients with EGFR gene mutation had liver and the possibility of bone metastasis.Attention should be paid to the reexamination of liver and bone during the course of treatment.The detection rate of POM121L12 in patients with brain metastasis was relatively high.This suggested a poor prognosis..The mutation might provide a new reference target for the further treatment of brain metastasis.4.The detection rate of FGFR1 in patients with central type Ⅲ B / Ⅳnon-small cell lung cancer is high,and the possibility of rare mutation is high.The mutation of FGFR1 gene mostly occurred in patients with squamous cell carcinoma of the lung,which was consistent with the characteristic that the central type of lung cancer was mostly squamous cell carcinoma.5.The possibility of EGFR gene mutation in non-smoking women.Smoking and early staging were more likely to lead to rare mutations in CDKN2 A.The mutation of EGFR and KRAS in patients with late staging was more likely.