ERCC1 And Class Ⅲ β-tubulin Protein Expression In Relation To Tumor Response And Survival Of Stage Ⅲ/Ⅳ NSCLC Patients Treated With TP/NP Chemotherapy

Cisplatin-based chemotherapy such as gemcitabine/platinum(GP),taxane/platinum(TP) and vinorelbine/platinum(NP) is currently considered to be standard chemotherapy(SC) for patients with non-small-cell lung cance(rNSCLC),but survival prospects and chemotherapy response rate(RR) remain disappointingly low for most NSCLC patients, and overall survival(OS),time tumor progression(TTP) and RR vary largely in same histology and stage NSCLC patients who received same chemotherapy regimen. The selection of SC regimens for NSCLC patients in clinic is in big blindness.With the development of pharmacogenomics techniques, some novel resist mechanisms and chemotherapy sensitivity molecular markers of different chemotherapy drugs are shown. The conventional SC regimens to NSCLC is beginning to shift towards the application of specific sensitivity molecular markers to tailor chemotherapy(TC) for individual NSCLC patients.In our trials,the relation between ERCC1, classⅢ?-Tubulin expression in tumor cells and chemotherapy sensitivity markers OS,TTP,RR in III/IV NSCLC patients receiving NP or TP regimens was demonstrated ,and our trials shows that the expression levels of ERCC1, classⅢ?-Tubulin in tumor cells is predictive of response to therapy and patient outcome in patients with III/IV NSCLC treated with platinum , taxane/vinorelbine respectively. The result of this study may provide new sight for TC to individual NSCLC patients. ( see part 1,part 2 and part 3) Part 1 ERCC1 protein expression in relation to chemotherapy sensitivity of stage III/IV NSCLC patients treated with cisplatin-based chemotherapyObjective Aim of this explorative study was to determine the prognostic value of protein expression of the DNA damage repair enzymes Excision Repair Cross-Complementing 1(ERCC1) for tumour response and survival of III/IV NSCLC patients treated with cisplatin-based chemotherapy.Methods A total of 120 III/IV NSCLC patients were included,only 53 patients were evaluated.Bronchoscopy tumour biopsies or lung puncture tumour biopsies were assessed in immunohistochemical staining using antibody against ERCC1 before chemotherapy.The patients were treated with 4 to 6 cycles of Cisplatin-based chemotherapy (taxane/cisplatin or vinorelbine/cisplatin). Patients characteristics such as sex,age,histology,stage ,PS score etc. were assessed before chemotherapy and chemotherapy tumor RR,OS,TTP were assessed afterwards.Results .A positive nuclear staining for ERCC1 was observed in 27 patients,the positive rate was 50.94 %. The clinical characteristics was similar between two groups .The overall response rate(RR), OS and TTP were 25.9%,294.78±127.52 days and 183.71±82.07 days in ERCC1 positive group respectively,and 53.8%, 415.50±204.75days and 261.04±134.34 days in ERCC1 negative group respectively,there were significant difference beween two groups(P=0.038,0.013 and 0.015 respectively),1-year survival rate was high in ERCC1 negative group,but there was no significant difference beween two groups (29.6% in ERCC1 positive group and 50% in ERCC1 negative group, P=0.130).Conclusion The different chemotherapy sensitivity might be the difference of expression of the DNA damage repair enzymes ERCC1 of NSCLC patients treated with cisplatin-based chemotherapy. PartⅡClassⅢβ-tubulin expression in tumor cells predicts response and outcome in stageⅢ/ⅣNSCLC receiving Taxanes or VinorebineObjective:Both fundamental and clinical studies suggest that classⅢβ-tubulin expression is associated with resistance to tubulin-binding agents such as vinorebine or taxanes, and classⅢβ-tubulin expression constitutes a prognostic foctor in several solid tumors.In our study,we assessed the prognostic and predictive value of classⅢβ-tubulin in tumors of patients withⅢ/ⅣNSCLC treated with taxanes-based regimens or vinorebine-based regimens.Methods: A total of 120 III/IV NSCLC patients were included,only 53 patients were evaluated Expression of classⅢβ-tubulin was examined immunohistochemically in tumor samples obtained by bronchoscopy or lung puncture before chemotherapy,including NSCLC patients received taxanes-based regimens or vinorebine-based regimens randomly. The patients were treated with 4 to 6 cycles of taxane/cisplatin or vinorelbine/cisplatin regimens. Patients characteristics such as sex,age,histology,stage ,PS score etc. were assessed before chemotherapy and RR,TTP,OS after chemotherapy.Result: The clinical characteristics was similar between two groups of the high and low levels expression of classⅢβ-tubulin,but patients whose tumors expressed low levels of classⅢβ-tubulin isotype had a longer TTP and OS( TTP 289.45±129.78 vs 170.06±71.45 days P<0.001 ,OS 457.32±207.12 vs 277.26±112.82 days P<0.001 respectively ),and patients whose tumors expressed low levels of classⅢβ-tubulin isotype had a better RR(59.09% vs 25.81%,P=0.015). Conclusion:Our trials suggest that the expression level of classⅢβ-tubulin in tumor cells is predictive of response to therapy and outcome in patients with NSCLC receiving tubuling-binding chemotherapy regimens. PartⅢERCC1,ClassⅢβ-Tubulin expression in tumor cells predicts response and outcome in stageⅢ/ⅣNSCLC patients teated with TP or NP regimensObjective:This trials was designed to determined whether ERCC1,ClassⅢβ-tubulin expression in tumor cells could predict response to chemotherapy and outcome in stageⅢ/ⅣNSCLC patients treated with tanaxe/cisplatin(TP) or vinorbine/cisplatin(NP) chemotherapy regimens.Methods: A total of 120 III/IV NSCLC patients were included,only 53 patients were evaluated .Bronchoscopy or lung puncture tumour biopsies samples were obtained and ERCC1 , ClassⅢβ-tubulin expression were examined immnohistochemically before chemotherapy respectively ,then the patients were randomly assigned to receive 4 to 6 cycles of TP or NP chemotherapy regimens.Follow-up was done afterwards until the patient died or could not be informed. RR,OS and TTP were assessed after chemotherapy.Result:According to different expression of ERCC1 and ClassⅢβ-tubulin,the patients were divided into 4 groups,P group(positive group,high expression of both ERCC1 and ClassⅢβ-tubulin),N group(negative group,low expression of both ERCC1 and ClassⅢβ-tubulin),T group(high expression of only ClassⅢβ-tubulin),E group (high expression of only ERCC1).OS and TTP differed significantly among 4 groups ( OS : P group:266.94±118.73days,N group:544.92±221.78days, T group:295.57±109.43days,E group:335.27±134.50 days respectively,P<0.001 ; TTP : P group:163.81±77.03days, N group:345.75±137.81days, T group 180.79±67.60days, E group:212.64±84.01days respectively,P<0.001),the OS and TTP were longer in negative group than that of other three groups,and there were no significant difference among othere three groups. The RR was better in negative group(66.67%) than that of other three groups(P 25.00%,T 35.71,E 36.36 P=0.037) and there were no significant among othere three groups.Conclusion: Our trials shows the expression level of ERCC1,classⅢβ-tubulin in tumor cells is predictive of response to therapy and outcome in patients with NSCLC receiving TP/NP chemotherapy regimens,it is suitable for NSCLC patients whose expression of both ERCC1 and ClassⅢβ-tubulin is low to adopt TP/NP chemotherapy regimens. The result of this study may provide new sight for TC to individual NSCLC patients.