NUDT expression is predictive of prognosis in patients with clear cell renal cell carcinoma

Abstract

Abstract. The nudix hydroxylase (NUDT) family of genes may have notable roles in cancer growth and metastasis. The present study aimed to determine the prognostic ability of NUDT genes in clear cell renal cell carcinoma (ccRCC). Data from 509 patients with ccRCC was obtained from The Cancer Genome Atlas (TCGA) database and 192 patient samples from Fudan University Shanghai Cancer Center (FUSCC) were analyzed in the present study. The expression profile of NUDT gene family members in the TCGA cohort was obtained from the TCGA RNA sequencing database. Pathological characteristics, including age, sex, tumor size, tumor grade, stage, laterality and overall survival were collected. Cox proportional hazards regression model and Kaplan-Meier survival analysis were performed to assess the associations between pathological characteristics and expression levels of NUDT family genes. NUDT family genes that exhibited associations with overall survival (OS) were further validated in the FUSCC cohort. In the TCGA cohort, Cox proportional hazards analysis found that NUDT5 [hazards ratio (HR)=1.676; 95% confidence interval (CI), 1.097-2.559] and NUDT17 (HR=1.375; 95% CI, 1.092-1.732) were predictive of ccRCC prognosis. Further analysis revealed that low NUDT5 (P<0.0001) and NUDT17 (P<0.0001) expression were associated with poorer OS rates in the TCGA cohort. In the FUSCC cohort, low NUDT5 expression was also associated with poor OS rates (P=0.0116), and tumor grade was a factor that influenced the expression level of NUDT5 (P=0.016).

Role of the NUDT Enzymes in Breast Cancer

“…In addition, knockdown of NUDT16 in Hela cells reduces cell proliferation [ 56 ]. NUDT5 was identified as an independent prognostic factor in colorectal cancer, associated with poor overall survival in clear cell renal carcinoma [ 57 ] and, in conjunction with high expression of MTH1, predicts poor survival in esophageal carcinoma [ 58 ].…”

Peer Review #1 of "The high expression of MTH1 and NUDT5 predict a poor survival and are associated with malignancy of esophageal squamous cell carcinoma (v0.2)"

“…The high expression of MTH1 was significantly correlated with the tumor pathological stage, lymph node metastasis and prognosis in non-smallcell lung carcinomas (Kennedy et al 2003). MTH1 expression is significantly higher in advanced-stage renal cell carcinoma than in early-stage renal cell carcinoma (Wang et al 2017b). In colorectal cancer, the levels of MTH1 and NUDT5 were significantly higher in CRC tissues from patients with an advanced AJCC stage and lymph node metastasis and were associated with an extremely poor OS after surgical resection (Li et al 2017).…”

“…However, in HeLa cells with inhibition of NUDT5, the cell cycle was arrested in the G1 phase, and the number of cells in the S and G2/M phases decreased (Carreras-Puigvert et al 2017). MTH1 and NUDT5 were reported to be associated with biological malignancy in various cancers (Li et al 2017;Wang et al 2017b). For patients with gastric cancer (GC), the overexpression of MTH1 was correlated closely with an increase in invasive depth and a decrease in the survival (Duan et al 2017).…”

Role of Differentially Expressed Proteins in Acquired Resistance to Cdk4/6 Inhibitor in Breast Cancer

“…DEPs are manually curated from the PubMed literature search engine to determine their molecular functions, roles in cancer progression, therapy resistance, and prognostic importance (see Table 1). NUDT5 is linked to a poor prognosis and low overall survival in clear cell renal cell carcinoma [23]. PEPD binds to Her-2 and inhibits EGFR signaling, resulting in cancer cell growth inhibition [24].…”