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

  • H. IgarashiEmail author
  • H. Taniguchi
  • K. Nosho
  • K. Ishigami
  • H. Koide
  • K. Mitsuhashi
  • K. Okita
  • I. Takemasa
  • K. Imai
  • H. Nakase
Research Article



Emerging 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.


We performed immunohistochemistry evaluations and assessed PRDM14 expression on 414 primary CRC specimens. Colon cancer cell lines were subjected to functional and stemness assays in vitro and in vivo.


We 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 independent 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.


Our 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.


Cancer stem cell Colorectal cancer Chemoresistance PRDM14 



Aldehyde dehydrogenase


Confidence interval


Colorectal cancer


Embryonic stem cell


Formalin-fixed, paraffin-embedded


Hazard ratio




Primordial germ cell


Positive regulatory domain I-binding factor 1 and retinoblastoma protein-interacting zinc finger gene 1 domain containing 14


Quantitative reverse transcription PCR


Standard deviation


Tumor invasion front



We thank the pathology departments of Sapporo Medical University Hospital and Keiyukai Sapporo Hospital for providing the tissue specimens. Writing assistance: the authors would like to thank Enago ( for English language review.

Author contributions

Study concept and design: HI, HT. Data acquisition: HI, KI1, HK, KM, KO, IT. Data analysis and interpretation: HI, HT, KN. Drafting of the manuscript: HI, KI1, HK, KM. Critical revision of the manuscript for important intellectual content: HT, KN, KO, IT, KI2, HN. Statistical analysis: HI. Final approval of manuscript: all authors.


This work was supported by the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research (Grant number 26860515 to H. I.), Takeda Science Foundation (to H. I.), Daiwa Securities Health Foundation (to H. I.), JSPS Grant-in-Aid for Scientific Research (Grant number 16K07145 to K. N.), and Japan Agency for Medical Research and Development (Grant number 16Ack0106108h0003 to H. T.). The funding bodies had no involvement in the design of the study, collection, analysis, and interpretation of data and in writing the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

This study was approved by the institutional review board of Sapporo Medical University Clinical trial center (reference number: 23-16), and was in accordance with the World Medical Association’s Declaration of Helsinki (1964, and its later amendments). All the animal studies were performed under the supervision of the Committee for Animal Research Center of Sapporo Medical University and in accordance with protocols approved by the Institutional Animal Care and Use Committee (reference number: 18-071).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

12094_2019_2239_MOESM1_ESM.doc (383 kb)
Supplementary file1 (DOC 383 kb)


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Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2019

Authors and Affiliations

  1. 1.Department of Gastroenterology and HepatologySapporo Medical University School of MedicineSapporoJapan
  2. 2.The Center for Antibody and Vaccine Therapy, Research Hospital, The Institute of Medical ScienceThe University of TokyoTokyoJapan
  3. 3.Department of Surgery, Surgical Oncology and ScienceSapporo Medical University School of MedicineSapporoJapan
  4. 4.The Institute of Medical ScienceThe University of TokyoTokyoJapan

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