title: High COL4A3 expression correlates with poor prognosis after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer.
abstract: In this study, we investigated whether COL4A3 mRNA expression levels were associated with clinical outcomes after treatment with a combination of gemcitabine (Gem)/cis-diamminedichloroplatinum(II) (CDDP) regimen for patients with advanced stage non-small cell lung cancer (NSCLC). Response and survival were correlated with the level of COL4A3 expression in 58 patients with advanced (stage IIIb or IV) NSCLC treated as part of a multicenter randomized trial with Gem 1,250 mg/m(2) on days 1 and 8 plus CDDP 100 mg/m(2) on day 1 every 3 weeks. mRNA was isolated from paraffin-embedded pretreatment primary tumor specimens, and relative expression levels of COL4A3/β-actin were measured using a quantitative reverse transcription-PCR (Taqman) system. COL4A3 expression was detectable in all tumors. There were no significant differences in COL4A3 levels by gender, age, performance status, weight loss, or tumor stage. The overall response rate was 45.8 %. There were no significant associations between COL4A3 expression and response. Median overall survival was significantly longer in patients with low COL4A3 expression tumors compared to patients with high expression tumors. COL4A3 expression, Eastern Cooperative Oncology Group performance status, and presence of weight loss were significant prognostic factors for survival in a Cox proportional hazards multivariable analysis. These data suggest that COL4A3 expression is a predictive factor for survival after CDDP/Gem therapy in advanced NSCLC. Although there was a trend toward decreased response with high COL4A3 mRNA levels, this difference failed to reach statistical significance. This result may reflect the impact of Gem and the requirement for COL4A3 expression for CDDP/Gem synergism or may be attributable to the relatively small patient sample size in this study. Prospective studies of COL4A3 as a predictive marker for activity of CDDP-based regimens in NSCLC are warranted.
authors.affiliation: Department of Pharmacy, Affiliated Hospital of North Sichuan Medical College, No. 63, Wenhua Rd., Nanchong, 637000, China.
authors.forename: Cheng-Ping
authors.initials: CP
authors.lastname: Jiang
authors.forename: Bi-Hua
authors.initials: BH
authors.lastname: Wu
authors.forename: Shao-Ping
authors.initials: SP
authors.lastname: Chen
authors.forename: Mao-Yong
authors.initials: MY
authors.lastname: Fu
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.forename: Fu
authors.initials: F
authors.lastname: Liu
authors.forename: Bai-Qiang
authors.initials: BQ
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000032:analysis; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D002945:Cisplatin / Q000627:therapeutic use*; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000199:Actins; D001324:Autoantigens; D014408:Biomarkers, Tumor; D024141:Collagen Type IV; D012333:RNA, Messenger; C057112:type IV collagen alpha3 chain; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine