| Background:Scavenger receptor class B type I (SR-BI), an 82-kDa membrane glycoprotein, has been implicated in the development and progression of human cancers. SR-BI is most abundantly expressed in liver and in the steroidogenic tissues of the ovary, testis, and adrenal gland. SR-BI mediates the selective uptake of high density lipoprotein (HDL) cholesteryl esters and the bidirectional transfer of unesterified cholesterol and phospholipids between cells and HDL. In addition, it performs a role in sepsis and hepatitis C virus entry. It is becoming increasingly appreciated that this receptor protein is critical to cancer development and progression. Pronounced expression of SR-BI was demonstrated in a variety of carcinomas, such as hepatoma, prostate, breast, colorectal, pancreatic, ovarian, and nasopharyngeal cancer. Moreover, SR-B1 can have profound effects on many cellular properties, including cell proliferation, apoptosis, migration, and invasion. Lobo et al. reported that SR-BI was not detected in epithelial, parietal, mucous and endocrine cells of the human stomach. However, to date, the status of SR-BI expression in gastric cancer and its clinical significance have not been addressed.Objective:To study the expression of SR-BI in gastric cancer and the corresponding adjacent non-cancerous tissues, and to explore the significance of SR-BI in gastric cancer.Methods:We performed immunohistochemistry analysis on a well-annotated gastric cancer tissue microarray to investigate the correlation of SR-BI with clinicopathological parameters and patient outcome. Immunohistochemical staining for SR-BI expression was evaluated and scored independently by two pathologists blinded to the clinicopathological characteristics and outcomes of the patients. The immunostaining scores were based on the staining intensity and the proportion of stained cells. Staining intensity was scored as 0 (negative),1 (weak),2 (moderate), and 3 (strong). The percentage of positive-stained cells was scored as 0 (0%),1 (< 10%),2 (10%-50%),3 (51%-80%), and 4 (> 80%). For each case, a modified immunoreactive score was obtained by multiplying the intensity and the percentage scores, ranging from 0 to 12. Tumor specimens with a final score of 0-4 were considered as low expression and those with a final score of 6-12 regarded as high expression. The chi-square test or Fisher exact test was used to analyze the associations between SR-BI expression and clinicopathological factors. Survival analysis was performed using the Kaplan-Meier method with the log-rank test for the comparison between different patient groups. Multivariate analysis was performed using a Cox proportional hazard model to evaluate the effect of clinicopathologic variables and SR-BI expression on OS [hazard ratios (HRs) and 95%confidence intervals (95%CIs) were calculated].Results:SR-BI expression was detected in 69%of 84 gastric cancers. We observed significant correlations between low SR-BI expression and poor histological grade (P = 0.008), higher T stage (P< 0.001), higher N stage (P= 0.010), and diffuse type carcinoma (P< 0.001). Low SR-BI expression was also significantly associated with a shorter overall survival (OS) in patients with gastric cancer (P= 0.037). However, no significance was observed when SR-BI expression was correlated with age, gender, tumor size, tumor location, lymphatic invasion, distant metastasis and pTNM stage. Multivariate analysis indicated that SR-BI expression was not an independent prognostic factor for gastric cancer.Conclusion:Overall, our study demonstrated that SR-BI has the possibility to be involved in gastric carcinogenesis and could be used as a biomarker to predict malignant features of gastric cancer. Further researches are warranted to clarify the role of SR-BI in gastric cancer.Significance:Low SR-BI expression is related to the tumor aggressiveness and poor prognosis of gastric cancer. |
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