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Jun 11, 2021;13 (12):

The Human TOR Signaling Regulator Is the Key Indicator of Liver Cancer Patients' Overall Survival: TIPRL/LC3/CD133/CD44 as Potential Biomarkers for Early Liver Cancers.

Soo Young Jun, Hyang Ran Yoon, Ji-Yong Yoon, Su-Jin Jeon, Jeong-Ju Lee, Debasish Halder, Jin-Man Kim, Nam-Soon Kim
Author Information
  1. Soo Young Jun: Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon 34141, Korea.
  2. Hyang Ran Yoon: Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon 34141, Korea.
  3. Ji-Yong Yoon: Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon 34141, Korea.
  4. Su-Jin Jeon: Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon 34141, Korea.
  5. Jeong-Ju Lee: Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon 34141, Korea.
  6. Debasish Halder: Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon 34141, Korea.
  7. Jin-Man Kim: Department of Pathology, Chungnam National University College of Medicine, Chungnam National University Hospital, 266 Munhwa-ro, Jung-gu, Daejeon 35015, Korea.
  8. Nam-Soon Kim: Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon 34141, Korea.
PMID: 34208132 DOI: 10.3390/cancers13122925

Abstract

Recently, we reported the involvement of TIPRL/LC3/CD133 in liver cancer aggressiveness. This study assessed the human TOR signaling regulator (TIPRL)/microtubule-associated light chain 3 (LC3)/prominin-1 (CD133)/cluster of differentiation 44 (CD44) as potential diagnostic and prognostic biomarkers for early liver cancer. For the assessment, we stained tissues of human liver disease/cancer with antibodies against TIPRL/LC3/CD133/CD44/CD46, followed by confocal observation. The roles of TIPRL/LC3/CD133/CD44/CD46 in liver normal and cancer cell lines were determined by in vitro studies. We analyzed the prognostic and diagnostic potentials of TIPRL/LC3/CD133/CD44/CD46 using the receiver-operating characteristic curve, a Kaplan-Meier and uni-/multi-Cox analyses. TIPRL and LC3 were upregulated in tissues of HCCs and adult hepatocytes-derived liver diseases while downregulated in iCCA. Intriguingly, TIPRL levels were found to be critically associated with liver cancer patients' survivability, and TIPRL is the key player in liver cancer cell proliferation and viability via stemness and self-renewal induction. Furthermore, we demonstrate that TIPRL/LC3/CD133 have shown prominent efficiency for diagnosing patients with grade 1 iCCA. TIPRL/LC3/CD133/CD44 have also provided excellent potential for prognosticating patients with grade 1 iCCA and grade 1 HCCs, together with demonstrating that TIPRL/LC3/CD133/CD44 are, either individually or in conjunction, potential biomarkers for early liver cancer.

Keywords

Kaplan–Meier analysis cluster of differentiation 44 (CD44) hepatocellular carcinomas (HCCs) human TOR signaling regulator (TIPRL) intrahepatic carcinomas (iCCA) liver cancer microtubule-associated light chain 3 (LC3) prominin-1 (CD133) receiver-operating characteristic (ROC) curve uni-/multi-Cox analyses

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Grants

  1. NRF-2020R1A2C2006752, 2014M3C9A2064618/National Research Foundation
  2. the Korea Research Institute of Bioscience and Biotechnology Research Initiative Program/the Korea Research Institute of Bioscience and Biotechnology Research Initiative Program
Journal Article

Word Cloud

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