ABSTRACT
Prohibitin, a potential tumor suppressor, has been shown to be an anti- proliferative protein, a regulator of cell-cycle progression and in apoptosis. Recently, it was found to be over-expressed in breast cancer and gastric cancer, and it has been suggested as a biomarker in those diseases. To clarify the role and the prognostic significance of prohibitin expression in esophageal squamous cell carcinoma (ESCC), we analyzed the expression in ESCC and their corresponding nonneoplastic epithelia tissues by immunohistochemistry(IHC), Western blotting and real-time quantitative reverse transcription polymerase chain reaction(QRT-PCR).The relationship between prohibitin expression and clinicopathological variables was examined by statistical analysis. The findings suggested the up-regulation of prohibitin play an important role in the carcinogenesis of ESCC. The over-expression of prihibitin was significantly correlated with the depth of tumor, lymph node metastasis, distant metastasis, lymphatic invasion and vascular invasion of ESCC. These results suggested that prohibitin(+), lymph node metastasis and distant metastasis could be the independent risk factors for worse prognosis in ESCC patients.
Subject(s)
Carcinoma, Squamous Cell/metabolism , Esophageal Neoplasms/metabolism , Repressor Proteins/biosynthesis , Adult , Aged , Analysis of Variance , Blotting, Western , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Chi-Square Distribution , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Female , Humans , Immunohistochemistry , Male , Middle Aged , Polymerase Chain Reaction , Prognosis , Prohibitins , Proportional Hazards Models , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Repressor Proteins/genetics , Repressor Proteins/metabolism , Survival Analysis , Tissue Array AnalysisABSTRACT
UNLABELLED: Stratifin plays an important role in cancer biology by interfering with intracellular signalling pathways and cell-cycle checkpoints. Decreased expression of stratifin gene has been reported to be a poor prognostic indicator in a variety of human malignant tumors. AIM: To clarify the role and prognostic significance of stratifin in esophageal squamous cell carcinoma (ESCC). METHODS: The alteration of stratifin messenger RNA (mRNA) and protein was analyzed by reverse-transcription and quantitative real-time polymerase chain reaction (QRT-PCR) and Western blotting in 20 paired ESCC and nonneoplastic esophageal mucosa tissues, respectively. Then, immunohistochemistry (IHC) was used to evaluate expression of stratifin in tissues of 148 ESCC patients (including the former 20 pairs of tissues) and correlate it with clinicopathological parameters and prognosis of ESCC patients. RESULTS: The stratifin level of mRNA and protein was markedly downregulated in ESCC tissue compared with in corresponding nonneoplastic esophageal epithelium (P<0.05). Similarly, the positive rate of stratifin protein expression was lower in the esophageal cancer than in paired nonneoplastic esophageal epithelium as detected by IHC (P=0.007). Statistically, the downregulation of stratifin expression was correlated with tumor infiltration depth (P=0.003), lymph node metastasis (P=0.008), distant metastasis (P=0.013), and lymphovascular invasion (P=0.007) of ESCC. Furthermore, the reduced stratifin expression was associated with shorter 5-year survival rate of ESCC patients after curative surgery (P<0.0001). On the basis of univariate and multivariate Cox regression analysis, we found that reduced stratifin expression, T4 stage, lymph node metastasis, and distant metastasis were independent risk factors for worse prognosis in ESCC patients. CONCLUSION: The present report indicates that stratifin could be a useful indicator for prognosis of this disease, as well as a potential target for more effective therapy.