Urotensin II receptor as a potential biomarker for the prognosis of hepatocellular carcinoma patients

Abstract

Urotensin II and the associated urotensin II receptor (UTR) are important in the carcinogenesis of hepatocellular carcinoma (HCC). However, the clinical significance of UTR remains to be elucidated. The aim of the present study was to investigate if UTR exhibits the potential to act as a biomarker to predict the prognosis of HCC patients. The effects of UTR on motility and invasion of HCC cells were additionally investigated. UTR expression levels were determined by immunohistochemistry, in 83 HCC patients that previously underwent curative liver resection. The association between UTR levels and clinicopathological data were analyzed. In vitro, the expressions of UTR in QSG-7701, BEL-7402 and MHCC-97H cell lines were determined via western blotting. Small interfering (si)RNA was used to downregulate UTR in BEL-7402 and MHCC-97H cell lines, and the effects of UTR on tumor cell motility were tested by Transwell assay. UTR expression was associated with tumor number, size, histology and tumor node metastasis/Barcelona Clinic Liver Cancer HCC stage. UTR expression levels were additionally associated with recurrence-free and overall survival in HCC patients by Kaplan-Meier curve analysis (P<0.0001). In vitro, UTR expression levels were increased in BEL-7402 and MHCC-97H cell lines, compared with QSG-7701 (P<0.05). siRNA-mediated silencing of the UTR gene significantly inhibited cell motility in BEL-7402 and MHCC-97H cells. The results indicated that UTR may be regarded as a novel biomarker to predict outcomes following radical liver resection and as a potential therapeutic target to inhibit invasion and metastasis of HCC.

Development of Novel 111-In-Labelled DOTA Urotensin II Analogues for Targeting the UT Receptor Overexpressed in Solid Tumours

“…Furthermore, hUII was able to increase the proliferation rate of both tumour cell lines only observable after 48 h period incubation, at low and high hUII concentrations ( Figure 5C). These data are in a good agreement with studies showing that UT and/or UII are over-expressed in a wide variety of solid tumours [41][42][43][44]58] and participate in tumorigenic mechanisms such as cell migration and/or proliferation. These data have been reported for cancers of prostate [59], colon [44], liver [79] and lung [48] cancers.…”

“…High-density UT has been reported in various tumour cell lines [40,41] as well as in human tumour extracts from lung [42], liver [43] and colon [44]. It has also been demonstrated that UII, at very low concentrations, stimulates cell proliferation and/or cell migration from human tumours, e.g., lung [45], colon [44], adrenal [40] cancers or high-grade gliomas [46,47].…”

Urotensin II receptor expression in prostate cancer patients: A new possible marker

“…Wei and colleagues recently showed how high UTII‐R expression is associated with worse prognostic outcomes in patients with hepatocellular carcinoma. More specifically both recurrence free (RR = 3.72; P = 0.001) and overall survival (RR = 4.58; P = 0.038) were significantly worse in patients with high UTII‐R expression . Conversely, in bladder cancer the evaluation of UTR expression can discriminate between NMIBC at high and low risk of relapse.…”

The Effect of Local Renin Angiotensin System in the Common Types of Cancer

“…It is also worth noting that, by encouraging VEGF to be produced and by intensifying HCC tumor growth and progression, UII may participate in tumor angiogenesis (85). It has been observed that HCC tissue has considerably high levels of UII and UII-R mRNA expression (85), which may activate migration and invasion within HCC as well (150,151). Furthermore, HCC is more likely to recur, invade, and metastasize following radical therapy due to the poor prognosis.…”

“…It has also been noted that, in HCC cases, UII-R expression is favorably related to tumor number, volume, histology, node metastasis, recurrence, and mortality. Hence, prognosis in HCC cases subjected to radical liver resection may be estimated based on UII-R level (151).…”