Research Paper Volume 13, Issue 10 pp 14015—14038

NUPR1 is a novel potential biomarker and confers resistance to sorafenib in clear cell renal cell carcinoma by increasing stemness and targeting the PTEN/AKT/mTOR pathway

NUPR1 upregulated is predominantly found in ccRCC and associated with poor prognosis. (A) Comparison of NUPR1 mRNA expression between ccRCC and normal kidney tissue from TCGA-KIRC dataset. (B) Relative mRNA level of NUPR1 in ccRCC cell lines compared with human renal proximal tubular epithelial cell line HK-2. (C) Western blot showed NUPR1 protein expression in ccRCC cell lines and HK-2. (D) Relative mRNA level of NUPR1 in twelve ccRCC tissues and paired normal kidney tissues. (E) Immunostaining of NUPR1 expression in 117 ccRCC tissues. Immunostaining intensity was scored as 0 negative, 1 weak positive, 2 moderate positive and 3 strong positive. (F) Overexpression of NUPR1 was associated with higher pathologic T stage, metastasis, elevated clinical stage and histologic grade in TCGA-KIRC dataset. (G) Kaplan-Meier curves of overall survival and disease-free survival time between low (n=135) and high (n=389) NUPR1 mRNA level groups in TCGA-KIRC dataset. The cutoff value was the mean of NUPR1 mRNA level in 524 ccRCC tissues. (H) Kaplan-Meier curves of overall survival and disease-free survival time between low (n=59) and high (n=58) NUPR1 immunostaining intensity groups in cohorts from Shandong Provincial Hospital. The median IHC score was used as the cutoff value. (*p p p

Figure 1. NUPR1 upregulated is predominantly found in ccRCC and associated with poor prognosis. (A) Comparison of NUPR1 mRNA expression between ccRCC and normal kidney tissue from TCGA-KIRC dataset. (B) Relative mRNA level of NUPR1 in ccRCC cell lines compared with human renal proximal tubular epithelial cell line HK-2. (C) Western blot showed NUPR1 protein expression in ccRCC cell lines and HK-2. (D) Relative mRNA level of NUPR1 in twelve ccRCC tissues and paired normal kidney tissues. (E) Immunostaining of NUPR1 expression in 117 ccRCC tissues. Immunostaining intensity was scored as 0 negative, 1 weak positive, 2 moderate positive and 3 strong positive. (F) Overexpression of NUPR1 was associated with higher pathologic T stage, metastasis, elevated clinical stage and histologic grade in TCGA-KIRC dataset. (G) Kaplan-Meier curves of overall survival and disease-free survival time between low (n=135) and high (n=389) NUPR1 mRNA level groups in TCGA-KIRC dataset. The cutoff value was the mean of NUPR1 mRNA level in 524 ccRCC tissues. (H) Kaplan-Meier curves of overall survival and disease-free survival time between low (n=59) and high (n=58) NUPR1 immunostaining intensity groups in cohorts from Shandong Provincial Hospital. The median IHC score was used as the cutoff value. (*p < 0.05, **p < 0.01, ***p < 0.001). (N.S., No statistical significance). ccRCC: clear cell renal cell carcinoma; KIRC: Kidney renal clear cell carcinoma; TCGA: The Cancer Genome Atlas database.