Downregulation of Macrophage-Derived T-UCR uc.306 Associates with Poor Prognosis in Hepatocellular Carcinoma

Cell Physiol Biochem. 2017;42(4):1526-1539. doi: 10.1159/000479269. Epub 2017 Jul 19.

Abstract

Background/aims: Increasing evidence suggests that T-UCRs are involved in the development of cancer. In this study, we evaluated the role of a macrophage-derived T-UCR, uc.306, in the prognosis of hepatitis B (HBV)-related hepatocellular carcinoma (HCC).

Methods: The uc.306 was obtained by screening microassay data obtained during the polarization of U937 cells from the M2 to M1 phenotype. Uc.306 and macrophage molecule markers were detected by qPCR. Immunohistochemical (IHC) assays were used to examine the M1/M2 status of 90 paired HCC tissues. Kaplan-Meier tests and multivariable Cox regression models were used to analyze predictive confidences, survival, and risk factors.

Results: In total, 2,977 differentially expressed T-UCRs were obtained, of which 257 showed fold changes >1.5. The uc.306 was upregulated in M1 cells and was predicted to be involved in the Wnt pathway. The IHC results showed that M1 macrophages (CD68+) were present in the para-tumor tissues, while the M2 phenotype (CD163+) was mainly in the HCC tissues. Uc.306 had a lower expression in the HCC tissues than in that of the para-tumor tissues in 30 paired HCC training sets (P < 0.0001), and 252 paired HCC testing sets (P < 0.0001). Low expression of uc.306 was significantly associated with a shorter overall survival (P < 0.05).

Conclusions: The uc.306 may be a promising biomarkerfor HBV-related HCC, providing a novel marker for the prognosis of HCC.

Keywords: Cancer survival; Hepatocellular carcinoma; Transcribed ultraconserved RNAs (T-UCRs); uc.306.

MeSH terms

  • Aged
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Proportional Hazards Models
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Risk Factors
  • Wnt Signaling Pathway

Substances

  • RNA, Long Noncoding