Pontin Acts as a Potential Biomarker for Poor Clinical Outcome and Promotes Tumor Invasion in Hilar Cholangiocarcinoma

Abstract

Hilar cholangiocarcinoma (HC) is a devastating malignancy that carries a poor overall prognosis. As a member of the AAA+ superfamily, Pontin becomes highly expressed in several malignant tumors, which contributes to tumor progression and influences tumor prognosis. In our research, Pontin expression in tumor specimens resected from 86 HC patients was detected by immunohistochemistry. Interestingly, high expression of Pontin was significantly associated with lymph node metastasis (p = 0.011) and tumor node metastasis (TNM) stage (p = 0.005). The Kaplan–Meier overall survival rate and multivariate analyses were performed to evaluate the prognosis of patients with HC. Patients with high Pontin expression had significantly poorer overall survival outcomes. Multivariate analyses found that Pontin was an independent prognostic factor (p = 0.001). Moreover, bioinformatics analysis confirmed the increase in Pontin mRNA expression levels in cholangiocarcinoma tissues. In addition, in vitro experiments showed that Pontin expression was inhibited at the mRNA as well as protein levels after transfection with Pontin siRNA in human cholangiocarcinoma cell lines. Moreover, significant suppression of cell invasion was observed after the downregulation of Pontin. Taken together, the present study suggested that Pontin could act as a potential prognostic predictor, which might be a new valuable molecular candidate for the prevention and treatment of HC.

High expression of RUVBL1 and HNRNPU is associated with poor overall survival in stage I and II non-small cell lung cancer patients

“…RUVBL1 staining differences between the histological subtypes of NSCLC may result from completely different underlying mechanisms driving the development of these tumors. Previous studies from other authors have reported that high RUVBL1 expression was significantly associated with the aggressive clinical features of cancer [ 24 , 27 ], but we did not observe any significant relationship. However, our study was limited by the number of subjects and the uneven distribution of the clinicopathological data.…”

“…Furthermore, by array CGH followed by validation with qPCR, Dehan et al demonstrated that RUVBL1 was located within the amplified region of 3q21 and overexpressed in NSCLCs [ 29 ]. In agreement with our studies, high expression of RUVBL1 was also shown in a variety of human solid tumors, such as colorectal [ 26 ], hilar cholangiocarcinoma [ 27 ], renal cell carcinoma [ 24 ], and hepatocellular carcinoma [ 28 ]. Therefore, we next asked whether RUVBL1 protein expression was associated with available clinicopathological factors, including histological type, gender, age, grade, pT, pN and TNM stage.…”

The Emerging Roles of ATP-Dependent Chromatin Remodeling Complexes in Pancreatic Cancer

“…Interacts with oncogene c-MYC and β-catenin. Roles in cell growth and viability [231][232][233][234][235][236][237][238]. In a mouse model of liver cancer, accumulation of E2f1 recruits the RUVBL1/RUVBL2 complex that opens the chromatin conformation at E2f target genes and amplifies the E2f transcriptional response during cancer progression.…”