J Korean Med Sci.  2016 Jun;31(6):879-885. 10.3346/jkms.2016.31.6.879.

Orai1 Expression Is Closely Related with Favorable Prognostic Factors in Clear Cell Renal Cell Carcinoma

• Lkhagvadorj S
• Kim JH
• Oh SS
• Lee MR
• Jung JH
• Chung HC
• Cha SK
• Eom M

• KMID: 2373696
• DOI: http://doi.org/10.3346/jkms.2016.31.6.879

Abstract

Store-operated calcium (Ca2+) entry (SOCE) is the principal Ca2+ 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.

Keyword

Orai1; STIM1; Carcinoma, Renal Cell; Kidney; Carcinogenesis; Prognosis

MeSH Terms

Adolescent
Adult
Aged
Blotting, Western
Carcinoma, Renal Cell/*diagnosis/metabolism/*pathology
Female
*Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Kidney Neoplasms/metabolism/*pathology
Male
Middle Aged
Neoplasm Proteins/genetics/metabolism
ORAI1 Protein/genetics/*metabolism
Prognosis
Retrospective Studies
Stromal Interaction Molecule 1/genetics/metabolism
Young Adult
Neoplasm Proteins
ORAI1 Protein
Stromal Interaction Molecule 1

Figure

• 

  Fig. 1 Immunohistochemistry (IHC) analysis of Orai1 and STIM1 in clear cell renal cell carcinoma (CCRCC). Expression of Orai1 (A) and STIM1 (B) in low and high grade tumors, respectively (×400). The mean staining score of IHC of Orai1 and STIM1 in Fuhrman nuclear grade 1-4 (C).

• 

  Fig. 2 Correlation of Orai1/STIM1 expression and tumor size. (A) Expression level of Orai1 in low and high grades, was analyzed with immunoblotting. (B) Relative (Rel.) expression of Orai1 in low and high grade tumor tissues. (C) Correlation between tumor size versus Orai1 negative and Orai1 positive groups. (D) Correlation between tumor size versus STIM1 negative and STIM1 positive groups; (NS) not significant. *P = 0.033 low vs. high grade tumors; †P < 0.01 Orai1 negative versus positive tumors.

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