High Expression of Stearoyl-CoA Desaturase 1 Predicts Poor Prognosis in Patients with Clear-Cell Renal Cell Carcinoma

Abstract

Stearoyl-CoA desaturase 1 (SCD1), the rate-limiting enzymes in the biosynthesis of monounsaturated fatty acids from saturated fatty acids, have been gradually recognized as a potential therapeutic target for various malignancies, particularly in clear-cell renal cell carcinoma (ccRCC). However, the prognostic value of SCD1 in ccRCC is still unknown. The aim of this study is to evaluate the clinical significance of SCD1 expression in patients with ccRCC. SCD1 expression in tumor tissues obtained from 359 patients who underwent nephrectomy for ccRCC are retrospectively assessed. During a median follow-up of 63 months (range: 1–144month), 56 patients in total died before the last follow-up in this study. Survival curves were plotted with the Kaplan–Meier method and compared with the log-rank test. Meanwhile, univariate and multivariate Cox regression models were applied to evaluate the prognostic value of SCD1 expression in overall survival (OS) for ccRCC patients. Moreover, SCD1 was enrolled into a newly built nomogram with factors selected by multivariate analysis, and the calibration was built to evaluate the predictive accuracy of nomogram. High SCD1 expression occurred in 61.6% (221/359) of ccRCC patients, which was significantly associated with age (p = 0.030), TNM stage (p = 0.021), pN stage (p = 0.014), Fuhrman grade (p = 0.014) and tumor sizes (p = 0.040). In multivariate analysis, SCD1 expression was confirmed as an adverse independent prognostic factor for OS. The prognostic accuracy of TNM stage, Fuhrman grade and tumor sizes was significantly increased when SCD1 expression was added. The independent prognostic factors, pT stage, pN stage, Fuhrman grade and tumor sizes, as well as SCD1 expression were integrated to establish a predictive nomogram with high predictive accuracy. Calibration curves revealed optimal consistency between observations and prognosis. In conclusion, high SCD1 expression is an independent prognostic factor for OS in patients with ccRCC. Our data suggest that the expression of SCD1 might guide the clinical decisions for patients with ccRCC.

Stearoyl-CoA Desaturase 1 as a Therapeutic Target for the Treatment of Cancer

“…Higher levels of MUFAs have also been found in transformed cells and cancerous tissue [14,15,16,17,18], and have been shown to modulate tumorigenic pathways [19,20,21]. Consistent with these findings, SCD1 expression is significantly elevated in various human cancer cells [22,23,24,25]. Moreover, this increase in SCD1 expression is positively correlated with cancer aggressiveness and poor patient prognosis in liver, thyroid, prostate, pancreatic, kidney, skin, and breast cancer [16,26,27,28,29].…”

Low level of isocitrate dehydrogenase 1 predicts unfavorable postoperative outcomes in patients with clear cell renal cell carcinoma

“…Five areas of IDH1 positive stains were selected to estimate at low (× 40) or high (× 200) magnification. The intensity was scored as: 0 (negative), 1 (weak), 2 (moderate), and 3 (strong); the percentage of cells was scored into the following four categories: 1 (0–25%), 2 (26–50%), 3 (51–75%), or 4 (> 75%), and comprehensive score = staining percentage × intensity [ 22 ]. Finally, the expression level of IDH1 was defined into low expression and high expression according to the comprehensive score (cutoff value = 6) [ 23 ].…”

Expression of SCD and FADS2 Is Lower in the Necrotic Core and Growing Tumor Area than in the Peritumoral Area of Glioblastoma Multiforme

“…For example, the induction of proliferation through transformation using simian virus 40 caused the increased expression of this enzyme [15]. SCD expression is also increased in neoplasms and is associated with worse prognosis for patients [16][17][18][19][20][21][22][23]56].…”

“…SCD also participates in the synthesis of fatty acids, the structural elements of cell membranes, and therefore, its expression increases in rapidly dividing cells [15]. SCD expression is elevated in the tumors of many cancers, including esophageal cancer [16,17], hepatocellular adenoma and carcinoma [16,18], colorectal cancer [16,17], breast cancer [17,19,20], gastric cancer [17], thyroid cancer [17,21], lung adenocarcinoma [19,22], prostate cancer [19,20], and clear-cell renal cell carcinoma [23]. Importantly, the increased tumor expression of SCD is associated with worse prognosis.…”