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.

MiR‐127‐3p inhibits cell growth and invasiveness by targeting ITGA6 in human osteosarcoma

“…For instance, miR‐429 was found down‐regulated in primary OS lesion and OS cell lines , miR‐3928 was down‐regulated in OS tissues and miR‐199a‐3p was expressed low in human OS cells . Further, according to previous studies, lower expression level of miR‐127‐3p was also found in OS , glioblastoma , and epithelial ovarian carcinoma , whereas ITGA6 was proved highly expressed in leukemia and gallbladder carcinoma .…”

Long noncoding RNA opa‐interacting protein 5 antisense transcript 1 promotes proliferation and invasion through elevating integrin α6 expression by sponging miR‐143‐3p in cervical cancer

“…ITGA6 has been demonstrated to be dramatically downregulated and to act as an oncogene in various cancers. For example, Zhang et al found that overexpression of ITGA6 was associated with invasion, metastasis, and poor prognosis in human gallbladder carcinoma . Brooks et al found that ITGA6 was directly regulated by hypoxia‐inducible factors and enriched for cancer stem cell activity and invasion in metastatic breast cancer models .…”

Genomic landscape of the immune microenvironments of brain metastases in breast cancer

“…The densely connected hub proteins are more likely to be essential proteins, which is referred to as the "centrality-lethality rule" [47]. THY1 is a glycophosphatidylinositol-anchored protein, which has been proposed to play important roles in cancers [48]. Function analysis showed that THY1 was signi cantly enriched in function associated with positive regulation of GTPase activity.…”