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Prognostic implication of SOX2 expression in small intestinal adenocarcinoma

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Abstract

The presence of KRAS mutation enhances the stem cell features of colorectal carcinoma cells containing mutant adenomatous polyposis coli (APC). However, their potential role in small intestinal adenocarcinoma remains elusive. Here, we aimed to investigate the clinical significance of cancer stem cell markers expression in the context of small intestinal adenocarcinoma with the KRAS genotype. SOX2, NANOG, and OCT4 expression were assessed by immunohistochemistry and digital image analysis, and their potential association with KRAS was further examined in 185 Korean patients with small intestinal adenocarcinomas, which were collected from 22 institutions in South Korea. Positive expression of SOX2, NANOG, and OCT4 was detected in 65 (35.1%), 94 (50.8%), and 82 (44.3%) of patients, respectively. Patients with high SOX2 (SOX2+) expression displayed worse overall survival compared to those with low SOX2 (SOX2−) expression (P < 0.001). Patients with SOX2+/mutant KRAS (KRASMT) (11.1 months) had significantly shorter overall survival than those with SOX2−/KRASWT (53.6 months) (P < 0.001). In multivariate analysis, SOX2+, distal location, high pT and pN categories, microsatellite stable, and absence of predisposing diseases were independent prognostic factors for worse overall survival. These results suggest that SOX2 expression has the potential to predict clinical outcomes in patients with small intestinal adenocarcinomas.

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Acknowledgments

We would like to thank the members of the Korean Small Intestinal Cancer Study Group: Dr. Eun Sun Jung, The Catholic University of Korea College of Medicine, Seoul; Dr. Young Kyung Bae, Yeungnam University College of Medicine, Daegu; Dr. Joon Mee Kim, Inha University College of Medicine, Incheon; Dr. Gwang Il Kim, CHA Bundang Medical Center, CHA University, Seongnam; Dr. Kee-Taek Jang, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Dr. Jung Yeon Kim, Inje University Sanggye Paik Hospital, Seoul; Dr. Soo Jin Jung, Inje University College of Medicine, Busan; Dr. Ghilsuk Yoon, Kyungpook National University School of Medicine, Daegu; Dr. Kyu Yun Jang, Chonbuk National University Medical School, Jeonju; Dr. Jinwon Seo, Hallym University Sacred Heart Hospital, Anyang; Dr. Tae Jung Kim, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul; Dr. Eun Kyoung Kwak, Fatima Hospital, Daegu; Dr. Dae Woon Eom, University of Ulsan College of Medicine, Gangneung Asan Hospital, Gangneung; Dr. Hee Kyung Kim, Soonchunhyang University Bucheon Hospital, Bucheon; Dr. Hee Sung Park, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul; and Dr. Ji Shin Lee, Chonnam National University Medical School, Gwangju, Korea.

Funding

This study was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and the Basic Science Research Program, through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (2017R1D1A1B03031817, awarded to S.-Y. J.).

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  1. Jeong Won Kim and Joon-Yong Chung contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Jeong Won Kim, Joon-Yong Chung, Kris Ylaya, Yoonho Park & Stephen M. Hewitt

  2. Department of Pathology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, 07441, Republic of Korea

    Jeong Won Kim

  3. Department of Pathology, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 21431, Republic of Korea

    Sun-Young Jun

  4. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05550, Republic of Korea

    Seung-Mo Hong

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Contributions

JWK, J-YC, S-MH, and SMH designed the study. JWK, J-YC, KY, and YP collected the data and analyzed the data. JWK and J-YC drafted and edited the manuscript. S-YJ, S-MH, and SMH reviewed and edited the manuscript.

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Correspondence to Seung-Mo Hong or Stephen M. Hewitt.

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The authors declare that they have no conflict of interest.

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This retrospective study was approved by the institutional review board of Incheon St. Mary’s Hospital (OC14OIMI0133), and patients’ informed consent was waived by the ethics committee.

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Kim, J.W., Chung, JY., Ylaya, K. et al. Prognostic implication of SOX2 expression in small intestinal adenocarcinoma. Virchows Arch 478, 1049–1060 (2021). https://doi.org/10.1007/s00428-020-02946-x

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