During this time, 120 patients with complete recorded information and paraffin sections were enrolled in our study, and followed-up for a minimum of three years. Written informed consent was obtained from all the patients. Thus, we aimed to evaluate the correlation between ABCG2 expression and overall survival of patients with clear cell RCC managed by renal surgery.įollowing approval by the Ethics Committee of Ruijin Hospital, the kidney surgery Registry database was used to identify patients who were managed with renal cancer surgery from 2008 to 2013. Clinically, whether ABCG2 expression could predict overall survival for RCC has not been well studied. Due to the heterogeneous high expression pattern of ABCG2 in the kidney, researchers have speculated that this protein may be actively involved in drug resistance, leading to failure of chemotherapeutic treatments. Īlthough ABCG2 has been studied in diverse fields, the precise function and effect in RCC are yet poorly understood. ABCG2 transports a wide variety of substrates including several anticancer agents and is one of the most significant contributors to multidrug resistance in cancer cells. Similar function of ABCG2 is validated in effluxing of xenobiotics at small intestine and kidney proximal tubule brush borders. ABCG2 has main effect on effluxing drugs at major physiological barriers, such as blood-brain, blood-testis and maternal-fetal barriers. Following its discovery, ABCG2 was cloned, characterized, and added as the second member of the G subfamily of ABC transporters, as a semi-transport protein. ĪTP-binding cassette sub-family G member 2 (ABCG2) was first named as Breast Cancer Resistance Protein in the 1990s when it was discovered in MCF-7 breast cancer cell line co-selected for doxorubicin in the presence of verapamil. However, the five-year overall survival for metastatic RCC remains <10%. By 2013, with the advancement in targeted therapy, such as Sunitinib and Sorafenib, the average survival time was improved from 12 months to 22 months in patients with metastatic RCC. Some cases respond to immunotherapy with a 30% response rate. RCC is relatively resistant to radiotherapy and chemotherapy with only a 4–5% response rate. To date, surgery is the primary treatment for RCC, and the five-year survival rate is 65–90% however, the outcome is considerably reduced in metastatic cases. Approximatelys, 25–30% patients present metastasis at the time of diagnosis and 30% of the patients relapse after renal surgery. Renal cell carcinoma (RCC) is the most common type of malignant renal cancer in adults, responsible for approximately 90–95% of the diagnosed cases. Further studies with large cohorts of patients will be essential for validating these findings and defining the clinical utility of ABCG2 in the patient population. The current data suggests that ABCG2 may serve as a prognostic marker for overall survival in patients with clear cell renal cell carcinoma. In the multivariable analysis, besides Fuhrman grade, the ABCG2 expression was an independent prognostic marker for overall survival ( p < 0.001) when incorporating other relevant tumor and clinical parameters (HR = 3.84, 95% CI: 1.92–7.70). ABCG2 expression significantly correlated with the five-year survival ( p < 0.001) and distant metastasis ( p = 0.001). Multivariable Cox regression evaluated the independent predictors for overall survival. The overall survival was analyzed using Kaplan-Meier method. Immunohistochemistry staining was performed to grade the expression of ABCG2 as ABCG2(−): less than 10% of tumor cells stained ABCG2(+): weak membrane staining and ABCG2(++): moderate or strong membrane staining. Methodsįrom 2008 to 2013, 120 patients with clear cell kidney cancer underwent surgery with paraffin-embedded specimens and necessary clinical information available. We aimed to evaluate the prognostic significance of ABCG2 expression in patients with clear cell renal cell carcinoma. ATP-binding cassette sub-family G member 2 (ABCG2) is a semi-transport protein that plays a major role in multidrug resistance.
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