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      • The expression of makorin ring finger protein 1 (MKRN1), pAKT, pmTOR, and PTEN in cervical neoplasias

        ( Han Byoul Cho ),( Joon Yong Chung ),( Mikiko Takikita ),( Stephen M Hewitt ),( Jae Hoon Kim ) 대한산부인과학회 2012 대한산부인과학회 학술대회 Vol.98 No.-

        The protein kinase B (AKT) pathway plays a key role in the regulation of cell death and survival, and has been proposed as a central signaling event in carcinogenesis. We investigated the expression of MKRN1, which is a transcriptional co-regulator and an E3 ligase, and sought to define the role of AKT pathway in cervical neoplasias. One hundred eighty three cervical cancer, 415 cervical intraepithelial neoplasia, and 400 matched nonadjacent normal tissues were arrayed into tissue microarrays. MKRN1, phosphorylated AKT (pAKT), phosphorylated mammalian target of rapamycin (pmTOR), and total phosphatase and tensin homolog deleted on chromosome 10 (PTEN) protein expressions were assessed by immunohistochemistry (IHC) and the relationship between MKRN1 expression and clinicopathologic parameters including survival data was studied. MKRN1, pAKT, and pmTOR expressions were significantly increased in cervical cancer cases compared with normal epitheliums (p<0.001 for all markers), and this increased expression of MKRN1 was significantly associated with tumor stage (p=0.018) and tumor grade (p<0.001). Expression of MKRN1 was positively associated with pAKT expression (p=0.023), while negatively associated with PTEN expression (p=0.016) in cervical cancer specimens. In multivariate analysis, MKRN1+/pAKT+ (HR = 4.76 [1.66-13.58], p=0.004), pAKT+ (HR = 2.97 [1.02-8.06], p=0.045), and lymph node metastasis (HR = 3.94 [1.07-14.45], p=0.039) were independent prognostic factors for overall survival. This study provides evidence of an association between AKT pathway and cervical carcinogenesis and shows that MKRN1/pAKT expression predicts poor prognosis in cervical cancer. Our findings also suggest that future research assessing its clinical usefulness would be worthwhile.

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