論文

国際誌
2022年1月30日

Phosphorylation of hTERT at threonine 249 is a novel tumor biomarker of aggressive cancer with poor prognosis in multiple organs.

The Journal of pathology
  • Yoko Matsuda
  • Taro Yamashita
  • Juanjuan Ye
  • Mami Yasukawa
  • Keiko Yamakawa
  • Yuri Mukai
  • Mitsuhiro Machitani
  • Yataro Daigo
  • Yohei Miyagi
  • Tomoyuki Yokose
  • Takashi Oshima
  • Hiroyuki Ito
  • Soichiro Morinaga
  • Takeshi Kishida
  • Toshinari Minamoto
  • Shinji Yamada
  • Junko Takei
  • Mika K Kaneko
  • Motohiro Kojima
  • Shuichi Kaneko
  • Tsutomu Masaki
  • Masahiro Hirata
  • Reiji Haba
  • Keiichi Kontani
  • Nobuhiro Kanaji
  • Nobuyuki Miyatake
  • Keiichi Okano
  • Yukinari Kato
  • Kenkichi Masutomi
  • 全て表示

257
2
開始ページ
172
終了ページ
185
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/path.5876

Recent evidence indicates that RNA-dependent RNA polymerase (RdRP) activity of human telomerase reverse transcriptase (hTERT) regulates expression of target genes and is directly involved in tumor formation by telomere independent manner. Non-canonical function of hTERT has been considered as a therapeutic target for cancer therapy. We have previously shown that hTERT phosphorylation at threonine 249 (p-hTERT), which promotes RdRP activity, is an indicator of an aggressive phenotype and poor prognosis in liver and pancreatic cancers, using two cohorts with small sample sizes with polyclonal p-hTERT antibody. To clarify the clinical relevance of p-hTERT, we developed a specific monoclonal antibody and determined the diagnostic and prognostic value of p-hTERT in cancer specimens using a large cohort. A monoclonal antibody for phosphorylated hTERT (p-hTERT) at threonine 249 was developed and validated. The antibody was used for the immunohistochemical staining of formalin-fixed paraffin-embedded specimens from 1,523 cases of lung, colon, stomach, pancreatic, liver, breast, and kidney cancers. We detected elevated p-hTERT expression levels in cases with a high mitotic activity, high pathological grade, and high nuclear pleomorphism. Elevated p-hTERT expression was an independent prognostic factor for lung, pancreatic, and liver cancers. Furthermore, p-hTERT expression was associated with immature and aggressive features, such as adenosquamous carcinoma (lung and pancreas), invasive type of cancer (lung), high serum alfa-fetoprotein level (liver), and triple-negative status (breast). In conclusion, RdRP activity indicated by p-hTERT expression predicts aggressive cancer phenotypes in various types of cancer. Thus, p-hTERT is a novel biomarker for the diagnosis of aggressive cancers with a poor prognosis. This article is protected by copyright. All rights reserved.

リンク情報
DOI
https://doi.org/10.1002/path.5876
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/35094384
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315154
ID情報
  • DOI : 10.1002/path.5876
  • PubMed ID : 35094384
  • PubMed Central 記事ID : PMC9315154

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