Abstract
STEAP1 (six transmembrane epithelial antigen of the prostate 1) is a transmembrane protein that functions as a potential channel or transporter protein. It is overexpressed in certain cancers and is viewed as a promising therapeutic target. However, the prognostic role of STEAP1 is still controversial, and no role for STEAP1 has yet been indicated in colorectal cancer. The aim of this study was to investigate the possible association of STEAP1 expression with colorectal cancer prognosis. STEAP1 expression was analyzed by immunohistochemical staining of a tissue array of 165 cancer specimens from primary colorectal cancer patients. The mean and medium follow-up times after surgery were 5.1 and 3.9 years, respectively. A total of 139 patients died during the 13 years of follow-up in the survey period. The prognostic value of STEAP1 with respect to overall survival was analyzed by Kaplan-Meier analysis and Cox proportional hazard models. In total, 164 samples displayed detectable STEAP1 expression in the cytoplasm and membrane. Low STEAP1 expression was correlated with poor overall survival (five-year survival: 33.7% vs. 57.0%, low expression vs. high expression, p = 0.020). Accordingly, multivariate analysis identified low STEAP1 expression as an independent risk factor (hazard ratio = 1.500, p = 0.018), especially in elderly patients or those with late stage cancers, late T values, and early N values. We suggest that analysis of STEAP1 expression by immunohistochemical staining could serve as an independent prognostic marker for colorectal patients. This finding should be validated by other investigative groups.
Highlights
A patient’s tumor stage at diagnosis is a key determinant of cancer prognosis and response to treatments [1]
We verified a role for STEAP1 in colorectal cancer patients by evaluating its expression in primary tumors from 165 patients
We investigated the influence of tu5moof r8 grade and histology on the prognostic role of STEAP1 by further adjusting for tumor grade, histology, awgieth, gleantedeTr,vaanludesst;aHgeR. =Th1e.7a1d8,ju9s5t%edCreI s=ul1t.s09co7–n2fi.6rm91e,dpt=ha0t.0lo18wfSoTr EpAatPie1netsxpwreitshsiaonn esatirlllypNredviacltueed, pToaobrlepr4ogannodsisFi(gHuRre=21B.5).92T, h9e5s%e CreIs=u1lt.s12c6o–n2f.i2r5m1,epd=a0.s0i0g9niffoicramntulptirvoagrniaotsetaicnavlaylsuise).fTohr eSsTeEfiAndPi1ngins spuagtigeensttsedwaithmsopreecfiafivcocrlainbilceoppraotghnoolosigsicfoalr cchoalorarecctetarilsctaicnsc.er patients with high STEAP1 expression
Summary
A patient’s tumor stage at diagnosis is a key determinant of cancer prognosis and response to treatments [1]. Tumor metastasis and recurrence negatively affect patient prognosis and quality of life [2]. The present study investigated the potential usefulness of STEAP1 in the prognosis of colorectal cancer patients. STEAP1, a 6-transmembrane protein, is expressed in normal tissues, but its expression is most abundant in prostate tissue [3,4]. It acts as an ion channel or transporter protein in tight junctions and gap junctions, or it can function in cell adhesion and intercellular communication [5]. A role in cell proliferation or anti-apoptosis is indicated, as blocking STEAP1 with a monoclonal antibody induces cell apoptosis [5]
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