Systematic expression alteration analysis of master reprogramming factor OCT4 and its three pseudogenes in human cancer and their prognostic outcomes

Sci Rep. 2018 Oct 4;8(1):14806. doi: 10.1038/s41598-018-33094-7.

Abstract

OCT4 is a master transcription factor that regulates the pluripotency of pluripotent stem cells and cancer stem cells along with other factors, including SOX2, KLF4, and C-MYC. Three different transcripts, OCT4A, OCT4B, and OCT4B1, are known to be generated by alternative splicing and eight OCT4 pseudogenes have been found in the human genome. Among them, we examined OCT4 and three pseudogenes (POU5F1P1, POU5F1P3, and POU5F1P4) because of their high expression possibility in cancer. In addition, previous studies indicated that OCT4 expression is augmented in cervical cancer and associated with poor prognosis, whereas OCT4 is down-regulated and correlated with good clinical outcomes in breast cancer. Because of these conflicting reports, we systematically evaluated whether expression of OCT4 and its pseudogenes can serve as oncogenic markers in various human cancers using the Oncomine database. Moreover, copy number alterations and mutations in OCT4 gene and its pseudogenes were analyzed using cBioPortal and the relationship between expression of OCT4 and pseudogenes and survival probability of cancer patients were explored using Kaplan-Meier plotter, OncoLnc, PROGgeneV2, and PrognoScan databases. Multivariate survival analysis was further conducted to determine the risk of the expression of the occurrence of OCT4 and its pseudogenes on certain cancer types using data from the Kaplan-Meier plotter. Overall, an association between expression of OCT4 and pseudogenes and cancer prognosis were established, which may serve as a therapeutic target for various human cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cellular Reprogramming / genetics*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kruppel-Like Factor 4
  • Mutation / genetics
  • Mutation Rate
  • Neoplasms / genetics*
  • Octamer Transcription Factor-3 / genetics*
  • Octamer Transcription Factor-3 / metabolism
  • Prognosis
  • Pseudogenes / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Survival Analysis

Substances

  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • Octamer Transcription Factor-3
  • RNA, Messenger