The first evidence for SLFN11 expression as an independent prognostic factor for patients with esophageal cancer after c
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RESEARCH ARTICLE
Open Access
The first evidence for SLFN11 expression as an independent prognostic factor for patients with esophageal cancer after chemoradiotherapy Takuma Kagami1* , Mihoko Yamade1, Takahiro Suzuki1, Takahiro Uotani1, Shinya Tani2, Yasushi Hamaya1, Moriya Iwaizumi3, Satoshi Osawa2, Ken Sugimoto1, Hiroaki Miyajima1, Satoshi Baba4, Haruhiko Sugimura5, Junko Murai6, Yves Pommier7 and Takahisa Furuta8
Abstract Background: Schlafen 11 (SLFN11) was recently identified as a dominant determinant of sensitivity to DNAtargeting agents including platinum-based drugs. SLFN11 also reportedly enhances cellular radiosensitivity. In this study, we examined the prognostic value of SLFN11 expression in esophageal squamous cell carcinoma (ESCC) patients treated with definitive chemoradiotherapy (dCRT), including the platinum derivative nedaplatin. Methods: Seventy-three patients with ESCC who received dCRT were examined. SLFN11 expression was analyzed in pre-dCRT biopsies using immunohistochemistry and evaluated using a histo-score (H-score). Correlation between the H-score and overall survival was analyzed. An H-score ≥ 51 was provisionally defined as indicating high SLFN11 expression. Viability assays were performed using previously established isogenic human cell lines differentially expressing SLFN11 to test the usefulness of SLFN11 as marker of response to the dCRT regimen. Results: High SLFN11 expression was independently associated with better prognosis in ESCC patients (hazard ratio = 0.295, 95% CI = 0.143–0.605, p = 0.001 for multivariate analysis). Kaplan-Meier survival curves showed that the prognostic value of high SLFN11 expression was most evident in patients at clinical stages II and III (p = 0.004). In in vitro study, SLFN11-proficient cells were highly sensitive to platinum derivatives compared to SLFN11-deficient cells. Conclusion: SLFN11 expression is an independent prognostic factor for ESCC patients treated with dCRT and a potential biomarker for treatment selection of ESCC. Examination of SLFN11 may be particularly useful for clinical Stage II–III patients who wish to choose dCRT (instead of surgery) to preserve esophageal function. Keywords: SLFN11, Esophageal cancer, Chemoradiotherapy, Biomarker, Nedaplatin, DNA damage
* Correspondence: [email protected] 1 First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu 431-3192, Japan Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line
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