Long noncoding RNA HOTTIP overexpression: A potential prognostic biomarker in prostate cancer

Yoo Jin Lee, Harim Oh, Eojin Kim, Bokyung Ahn, Jeong Hyeon Lee, Youngseok Lee, Yang Seok Chae, Sung Gu Kang, Chul Hwan Kim

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Abstract

HOXA transcript at the distal tip (HOTTIP) is a long noncoding RNA (lncRNA), which is >200 nucleotides in length. HOTTIP expression has been demonstrated to play a crucial oncogenic role in cancer pathogenesis, and is said to be associated with poor human cancer prognosis. In prostate cancer, HOTTIP has been identified as an oncogene, but its clinicopathologic significance remains unclear. Array-based qRT-PCR was used to investigate lncRNA levels in 10 pairs of prostate cancer tissues and non-neoplastic parenchyma. Tissue microarray (TMA) was constructed using a total of 70 surgically resected prostatic adenocarcinoma tissues obtained from the Korea University Anam Hospital from 2009 to 2013. HOTTIP expression was determined by RNA in situ hybridization(ISH) and was correlated with clinicopathologic features. Increased HOTTIP expression was observed in all available prostate cancer tissue specimens compared with that in paired normal tissue. High HOTTIP expression was positively associated with bad clinicopathologic features, including higher pathologic T stage (p < 0.001), presence of extraprostatic extension (p < 0.001), seminal vesicle invasion (p < 0.001), perineural invasion (p < 0.001), and the tumor involvement of resection margin (p = 0.044). In particular, significantly increased HOTTIP expression was observed in specimens from patients in the high or very high-risk group, according to the 2018 National Comprehensive Cancer Network (NCCN) guidelines (p < 0.001). Also, patients with high HOTTIP expression showed poorer overall survival than those with low expression. In conclusion, we analytically validated the poor prognostic significance of HOTTIP overexpression and its association with bad clinicopathologic features, and present HOTTIP as a potential prognostic biomarker in prostate cancer.

Original languageEnglish
Article number152649
JournalPathology Research and Practice
Volume215
Issue number11
DOIs
Publication statusPublished - 2019 Nov

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Keywords

  • HOXA transcript at the distal tip
  • In situ hybridization
  • Long noncoding RNA
  • Prostate cancer

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology

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