Identification of NCCRP1 as an epigenetically regulated tumor suppressor and biomarker for malignant phenotypes of squamous cell carcinoma of the esophagus

Abstract

Abstract. The poor prognosis and increasing incidence of esophageal squamous cell carcinoma (ESCC) highlight the need for identification of novel ESCC-associated molecular events to improve the diagnosis, and treatment of this disease. Non-specific cytotoxic cell receptor protein 1 (NCCRP1) was reported to be abundantly expressed in human squamous epithelium and to be involved in cell proliferation; however, the role of NCCRP1 in ESCC remains unclear. To elucidate the oncological roles of NCCRP1 in ESCC, NCCRP1 expression, DNA methylation, and copy numbers were analyzed in ESCC cell lines. Nine ESCC cell lines demonstrated different NCCRP1 mRNA expression levels and all exhibited hypermethylation of the NCCRP1 promoter, but no copy number loss. Additionally, NCCRP1 expression was determined in 213 surgically resected esophageal tissue samples. NCCRP1 mRNA expression levels were reduced in ESCC tissues compared with corresponding non-cancerous adjacent tissues in 204 (95.8%) patients. Patients in the low NCCRP1 expression group tended to have a higher recurrence rate and a shorter overall survival time compared with those in the high NCCRP1 expression group. Additionally, multivariate analysis revealed that low NCCRP1 expression was an independent prognostic factor (hazard ratio, 1.75; 95% confidence interval, 1.08-2.87; P= 0.022). The findings of the current study indicate that NCCRP1 acts as a putative tumor suppressor that is inactivated through promoter hypermethylation, and serves as a promising biomarker to predict postoperative prognosis in ESCC.

A Novel Gene Prognostic Signature Based on Differential DNA Methylation in Breast Cancer

“…Moreover, the methylation level of SEC61G was positively correlated with the prognosis of patients with glioma ( Liu et al, 2019a ). Miwa et al proved that NCCRP1 transcription was inhibited by promoter hypermethylation in esophageal squamous cell carcinoma ( Miwa et al, 2017 ). And high expression of NCCRP1 in patients with pancreatic cancer was associated with a poor prognosis ( Zuo et al, 2020 ).…”

Identification of a Ubiquitination-Related Gene Risk Model for Predicting Survival in Patients With Pancreatic Cancer

“…CDC27 promotes the progression and affects PD-L1 expression in T-cell lymphoblastic lymphoma, and also promotes epithelial-to-mesenchymal transition in colorectal cancer ( Qiu et al, 2017 ; Song et al, 2020 ). There are few studies on the role of NCCRP1, RNF25, and UBE2H in cancer, but the existing research results suggest that these three genes also have the potential to become new tumor biomarkers or targets for cancer ( Miwa et al, 2017 ; Cho et al, 2018 ; Zhu et al, 2018 ).…”

Cancer Stem Cell Transcriptome Landscape Reveals Biomarkers Driving Breast Cancer Heterogeneity

“…For example, we previously reported the suppressive role of FOXA1 on breast cancer stemness [17]; SOX9 is as a stem cell factor [18] that drives the epithelial mesenchymal transition (EMT) in non-small cell lung cancer through Wnt pathway [19] and maintains human breast luminal progenitor and breast cancer stem cells through SOX9 mediated signaling [20], and both the SOX9/FXYD3/SRC [21] and the SOX9/SOX2 [20] axes are critical for breast cancer stem cell functionalities; PLA2G7 is associated with ER negativity in clinical breast cancer samples and regulates EMT in vitro [22]. The prognostic values of several markers have been reported, including PTPN6 and KRT19 in breast cancers [23][24][25], EPPK1 in non-small cell lung cancers [26], SERPINB5 in colorectal cancers [27], and NCCRP1 in squamous cell carcinoma [28]. Besides, the roles of S100A7 and SLC37A1 was implicated in breast cancers [29,30], that of SERPINB4 was reported in squamous cell carcinoma [31], and that of MYH14 was lately identi ed in pancreatic cancers [32].…”