| Background and ObjectivesCurrently, stomach cancer, that about one million new cases of stomach cancer wereestimated to have occured in2008, is detected as the fourth most common malignancy in theworld, behind cancers of the lung, breast and colo-rectum. The incidence of gastric cancershows an enigmatic male dominance with a male-to-female ratio of about2:1. This sex ratiocannot be entirely attributed to the differences in the prevalence of known risk factorsbetween the sexes. Sex hormone receptors (such as Estrogen receptor, ER; Progesteronereceptor, PR; Androgen receptor, AR), members of the nuclear intracellular receptorssubfamily, are involved in many physiological functions. Recent work has shown that theyplays as an important role in cancer development and progression. However, seldom havetheir status in gastric cancer been cleared. They are regarded as tumor biological markers,which are closely linked to the occurrence and development of gastric tumors, and haveimportant significance in the metastasis and prognosis of stomach neoplasms. Compared withother anti-cancer drugs, sex hormone receptor-related drugs have a high specificity and minoradverse effects, which show a broad prospect for clinical application.The present study intended to clarify the clinical significance of sex hormone receptorsexpression in human gastric cancer.MethodsTissue microarray (TMA) blocks were constructed based on1,072Chinese patients,containing both gastric cancer tissues and adjacent normal mucosa tissues. The expression ofsex hormone receptors was analyzed from both mRNA and protein level, by Real-timequantitative polymerase chain reaction (RT-PCR), Western blotting, andimmunohistochemistry (IHC). Different expressions of sex hormone receptors mRNA intumor tissues and matched normal tissues were analyzed with the student’s T test, and theassociation between sex hormone receptors and the clinicopathological features wascalculated by Chi-square test or Fisher’s exact test (if necessary). The relationship betweenexpression of sex hormone receptors and prognosis was analyzed by Kaplan-Meier methodand the Cox proportional hazard regression model. ResultsThe expression of sex hormone receptors, such as ERα, ERβ, PR and AR, were found in bothgastric cancer tissues and adjacent non-cancerous tissues. In the tissues that could probablybe assessed, one hundred and two (12.00%) of848gastric cancer tissues were positive forERα, seven hundred and fifty six of822(91.90%) were positive for ERβ, two hundred andseventy eight of843(33.00%) were positive for AR, and one hundred and ninty eight of851(23.30%) were positive for PR in cancerous tissues. The expression of each sex hormonereceptor in gastric tumor was all significantly lower than that expressed in normal gastricmucosa （P≤0.001）. As the same, in18pairs of gastric cancer tissue and their matchedadjacent normal mucosa, sex hormone receptors mRNA was significantly reduced in tumorspecimens compared with adjacent normal tissues. Significant differences were observed inthe relationship between differentiation and sex hormone receptors’ expression（P <0.05）.And the expression of ERα and AR was associated with depth of invasion, status of lymphnodes and TNM stage（P≤0.001）. With the univariate survival analysis, Kaplan–Meiersurvival curves demonstrated that ERα-positive patients had better median survival time thanERα-negative patients (MST：81.5months V.S43.0months, P≤0.001). Meanwhile,AR-positive patients also had better median survival time than AR-negative patients (MST：71.0months V.S40.0months, P=0.028).ConclusionsThis study revealed the clinical significance of expression of sex hormone receptors,providing a basis for a novel negative biomarker in gastric cancer progression and prognosis.Furthermore, sex hormone receptors might be considered to be a potential differentiationmarker. The positive expression of the four receptors was associated with tumor grade buttheir prognostic value was limited. |
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