title: Overexpression of Thy1 and ITGA6 is associated with invasion, metastasis and poor prognosis in human gallbladder carcinoma.
abstract: Gallbladder cancer (GBC) is a rare but highly aggressive cancer for which no well-accepted prognostic biomarkers have been identified. Thymus cell antigen 1 (Thy1), also known as cluster of differentiation (CD)90, and integrin α6 (ITGA6), also known as CD49f, are important molecules in cancer and putative markers of various stem cell types. However, their role in GBC remains to be elucidated. In the present study, Thy1 and ITGA6 expression status in clinical GBC samples, which comprised squamous cell/adenosquamous carcinoma (SC/ASC) and adenocarcinoma (AC) subtypes, was investigated. The associations between Thy1 and ITGA6 expression and clinical parameters and survival rate were analyzed separately. The THY1 and ITGA6 messenger RNA levels were significantly higher in both SC/ASC and AC tissues than in adjacent non-tumor tissues (all P<0.001). These results were subsequently confirmed by immunohistochemical analyses. Overexpression of Thy1 and ITGA6 was correlated with poor differentiation, large tumor size, lymph node metastasis and great invasiveness in SC/ASC (Thy1, P=0.045, P=0.005, P=0.003 and P=0.009, respectively, and ITGA6, P=0.029, P=0.011, P=0.009 and P=0.004, respectively) and AC (Thy1, P=0.027, P<0.001, P=0.003 and P 0.004, respectively, and ITGA6, P=0.002, P=0.003, P=0.006 and P=0.006, respectively). Both Thy1 and ITGA6 were expressed at higher levels in AC with advanced tumor-node-metastasis stage (TNM) than in AC with low TNM stage (P=0.001 and P=0.018, respectively). In addition, patients with elevated Thy1 or ITGA6 expression had shorter overall survival than those with negative Thy1 or ITGA6 expression. Multivariate Cox regression analysis demonstrated that Thy1 (SC/ASC, P=0.001 and AC, P=0.005) and ITGA6 (both P=0.003) were independent predictors of poor prognosis in both SC/ASC and AC patients. In conclusion, Thy1 and ITGA6 could be clinical prognostic markers for GBC.
authors.affiliation: Research Laboratory of Hepatobiliary Diseases, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Dan-Hua
authors.initials: DH
authors.lastname: Zhang
authors.affiliation: Research Laboratory of Hepatobiliary Diseases, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Zhu-Lin
authors.initials: ZL
authors.lastname: Yang
authors.affiliation: Research Laboratory of Hepatobiliary Diseases, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: En-Xiang
authors.initials: EX
authors.lastname: Zhou
authors.affiliation: Research Laboratory of Hepatobiliary Diseases, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Xiong-Ying
authors.initials: XY
authors.lastname: Miao
authors.affiliation: Department of Pathology, Changde Central Hospital, Changde, Hunan 415000, P.R. China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zou
authors.affiliation: Department of Pathology, Basic Medical Science College, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Jing-He
authors.initials: JH
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Hunan Provincial People's Hospital, Changsha, Hunan 410007, P.R. China.
authors.forename: Lu-Feng
authors.initials: LF
authors.lastname: Liang
authors.affiliation: Department of Pathology, Loudi Central Hospital, Loudi, Hunan 417011, P.R. China.
authors.forename: Gui-Xiang
authors.initials: GX
authors.lastname: Zeng
authors.affiliation: Department of Pathology, Hunan Provincial Tumor Hospital, Changsha, Hunan 410013, P.R. China.
authors.forename: Sen-Lin
authors.initials: SL
authors.lastname: Chen
keywords: ITGA6; Thy1; gallbladder carcinoma; prognostic markers