PRDM14 promotes malignant phenotype and correlates with poor prognosis in colorectal cancer

• H. Igarashi ^[1] ; H. Taniguchi ^[2] ; K. Nosho ^[1] ; K. Ishigami ^[1] ; H. Koide ^[1] ; K. Mitsuhashi ^[1] ; K. Okita ^[1] ; I. Takemasa ^[1] ; K. Imai ^[3] ; H. Nakase ^[1]
  1. [1] Sapporo Medical University

     Sapporo Medical University

     Chūō-ku, Japón

     
  2. [2] University of Tokyo

     University of Tokyo

     Japón

     
  3. [3] The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 22, Nº. 7, 2020, págs. 1126-1137
• Idioma: inglés
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• Resumen

  • BackgroundEmerging evidence suggests that stemness in cancer cells is a cause of drug resistance or metastasis and is an important therapeutic target. PR [positive regulatory domain I-binding factor 1 (PRDI-BF1) and retinoblastoma protein-interacting zinc finger gene (RIZ1)] domain containing 14 (PRDM14), that regulates pluripotency in primordial germ cell, has reported the overexpression and function of stemness in various malignancies, suggesting it as the possible therapeutic target. However, to our knowledge, there have been no reports on the expression and function of PRDM14 in colorectal cancer (CRC). Therefore, we investigated the expression and the role of PRDM14 in CRC.MethodsWe performed immunohistochemistry evaluations and assessed PRDM14 expression on 414 primary CRC speci-mens. Colon cancer cell lines were subjected to functional and stemness assays in vitro and in vivo.ResultsWe found that PRDM14 positive staining exhibited heterogeneity in the CRC primary tumor, especially at the tumor invasion front. The aberrant expression of PRDM14 at the invasion front was associated with lymph node metastasis and disease stage in patients with CRC. Furthermore, the multivariate analysis revealed high PRDM14 expression as an independ-ent prognostic factor in the patients with Stage III CRC. Overexpression of PRDM14 enhanced the invasive, drug-resistant and stem-like properties in colon cancer cells in vitro and tumorigenicity in vivo.ConclusionOur findings suggest that PRDM14 is involved in progression and chemoresistance of CRC, and is a potential prognostic biomarker and therapeutic target in the CRC patients.