Elevated expression of RIT1 correlates with poor prognosis in endometrial cancer

RIT1, (Ras-like without CAAX1), the founding member of a novel branch of the Ras subfamily, mediates a wide variety of cellular functions, including cell proliferation, survival, and differentiation, and it may play crucial oncogenic role in human cancer. The purpose of the current study was to char...

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Published in:International journal of clinical and experimental pathology 2015-01, Vol.8 (9), p.10315-10324
Main Authors: Xu, Fengjuan, Sun, Su'an, Yan, Shilan, Guo, Hongling, Dai, Miao, Teng, Yincheng
Format: Article
Language:English
Subjects:
Adult
Carcinoma - genetics
Carcinoma - metabolism
Carcinoma - mortality
Carcinoma - pathology
Cell Differentiation - genetics
Cell Line, Tumor
Cell Proliferation - genetics
Cell Survival - genetics
Disease Progression
Endometrial Neoplasms - genetics
Endometrial Neoplasms - metabolism
Endometrial Neoplasms - mortality
Endometrial Neoplasms - pathology
Female
Humans
Middle Aged
Neoplasm Staging
Original
Prognosis
ras Proteins - genetics
ras Proteins - metabolism
Survival Rate
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Summary:RIT1, (Ras-like without CAAX1), the founding member of a novel branch of the Ras subfamily, mediates a wide variety of cellular functions, including cell proliferation, survival, and differentiation, and it may play crucial oncogenic role in human cancer. The purpose of the current study was to characterize the expression pattern of RIT1 and assess the clinical significance of RIT1 expression in endometrial cancer patients. The mRNA and protein expression of RIT1 was significantly overexpressed in 7 endometrial cancer cell lines by qPCR and Western blot, respectively. In addition, RIT1 mRNA expression was elevated in 36 freshly frozen endometrial cancer tissues compared to 21 non-cancerous endometrial tissue samples. Similar results were observed by analyzing GEO datasets. Immunohistochemistry was used to examine the protein expression of RIT1 in two tissue microarrays containing 257 cases of tumor and 31 non-tumor tissues, which showed that elevated expression of RIT1 was significantly correlated with pathological type, clinical stage, grade and vascular invasion. Importantly, Kaplan-Meier survival analysis indicated that RIT1 expression was associated with overall survival of endometrial cancer patients. Multivariate Cox regression analysis revealed that RIT1 expression was one of the independent prognostic factors for endometrial cancer patients. Furthermore, RIT1 combined with other clinicopathological risk factors was a more significant model in ROC curve comparison. In conclusion, elevated expression of RIT1 may contribute to the progression of endometrial cancer and thus may serve as a novel prognostic marker and a promising molecular target for the treatment of endometrial cancer.
ISSN:1936-2625