title: Orai1 Expression Is Closely Related with Favorable Prognostic Factors in Clear Cell Renal Cell Carcinoma.
abstract: Store-operated calcium (Ca(2+)) entry (SOCE) is the principal Ca(2+) entry route in non-excitable cells, including cancer cells. We previously demonstrated that Orai1 and STIM1, the molecular components of SOCE, are involved in tumorigenesis of clear cell renal cell carcinoma (CCRCC). However, a clinical relevance of Orai1 and STIM1 expression in CCRCC has been ill-defined. Here, we investigated the expression of Orai1 and STIM1 in CCRCC, and compared their expression with clinico-pathological parameters of CCRCC and the patients' outcome. Immunohistochemical staining for Orai1 and STIM1 was performed on 126 formalin fixed paraffin embedded tissue of CCRCC and western blot analysis for Orai1 was performed on the available fresh tissue. The results were compared with generally well-established clinicopathologic prognostic factors in CCRCC and patient survival. Membrane protein Orai1 is expressed in the nuclei in CCRCC, whereas STIM1 shows the cytosolic expression pattern in immunohistochemical staining. Orai1 expression level is inversely correlated with CCRCC tumor grade, whereas STIM1 expression level is not associated with tumor grade. The higher Orai1 expression is significantly associated with lower Fuhrman nuclear grade, pathologic T stage, and TNM stage and with favorable prognosis. The expression level of STIM1 is not correlated with CCRCC grade and clinical outcomes. Orai1 expression in CCRCC is associated with tumor progression and with favorable prognostic factors. These results suggest that Orai1 is an attractive prognostic marker and therapeutic target for CCRCC.
authors.affiliation: Department of Pathology, Yonsei University Wonju College of Medicine, Wonju, Korea.; Department of Pathology, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia.
authors.forename: Sayamaa
authors.identifier: 0000-0001-6924-8715
authors.initials: S
authors.lastname: Lkhagvadorj
authors.affiliation: Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Korea .
authors.forename: Ji-Hee
authors.identifier: 0000-0002-7980-4014
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Occupational & Environmental Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea .
authors.forename: Sung-Soo
authors.identifier: 0000-0003-0801-3052
authors.initials: SS
authors.lastname: Oh
authors.affiliation: Department of Pathology, Yonsei University Wonju College of Medicine, Wonju, Korea .
authors.forename: Mi-Ra
authors.identifier: 0000-0001-5137-6364
authors.initials: MR
authors.lastname: Lee
authors.affiliation: Department of Urology, Yonsei University Wonju College of Medicine, Wonju, Korea .
authors.forename: Jae Hung
authors.identifier: 0000-0002-4990-7098
authors.initials: JH
authors.lastname: Jung
authors.affiliation: Department of Urology, Yonsei University Wonju College of Medicine, Wonju, Korea .
authors.forename: Hyun Chul
authors.identifier: 0000-0002-3450-7817
authors.initials: HC
authors.lastname: Chung
authors.affiliation: Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Korea.; Department of Global Medical Science, Yonsei University Wonju College of Medicine, Wonju, Korea.; Institute of Lifestyle Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Seung-Kuy
authors.identifier: 0000-0003-3201-7950
authors.initials: SK
authors.lastname: Cha
authors.affiliation: Department of Pathology, Yonsei University Wonju College of Medicine, Wonju, Korea .
authors.forename: Minseob
authors.identifier: 0000-0002-8121-8399
authors.initials: M
authors.lastname: Eom
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D000071740:ORAI1 Protein / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies; D000071737:Stromal Interaction Molecule 1 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1
keywords: Carcinogenesis; Carcinoma, Renal Cell; Kidney; Orai1; Prognosis; STIM1