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    Title: Overexpression of Dehydrogenase/Reductase 9 Predicts Poor Response to Concurrent Chemoradiotherapy and Poor Prognosis in Rectal Cancer Patients
    Authors: Chen, Tzu-Ju
    Hsu, Bei-Hao
    Lee, Sung-Wei
    Yang, Ching-Chieh
    Tian, Yu-Feng
    Kuo, Yu-Hsuan
    Li, Wan-Shan
    Tsai, Hsin-Hwa
    Wu, Li-Ching
    Yeh, Cheng-Fa
    Chou, Chia-Lin
    Lai, Hong-Yue
    Contributors: Chi Mei Hospital
    Chung Hua University
    Chung Shan Medical University
    Chung Shan Medical University Hospital
    Department of Pharmacy, Chia Nan University of Pharmacy & Science
    Chia Nan University of Pharmacy & Science
    National Sun Yat Sen University
    Chi Mei Hospital
    China Medical University Taiwan
    China Medical University Hospital - Taiwan
    Chia Nan University of Pharmacy & Science
    Keywords: keratan sulfate
    expression
    glycosaminoglycan
    differentiation
    muc2
    Date: 2022
    Issue Date: 2023-12-11 14:04:41 (UTC+8)
    Publisher: FRONTIERS MEDIA SA
    Abstract: Objective: To reduce the risk of locoregional recurrence, the addition of neoadjuvant concurrent chemoradiotherapy (CCRT) is recommended before surgical management for rectal cancer patients. However, despite identical tumor histology, individual patient response to neoadjuvant CCRT varies greatly. Accordingly, a comprehensive molecular characterization that is used to predict CCRT efficacy is instantly needed.Methods: Pearson's chi-squared test was utilized to correlate dehydrogenase/reductase 9 (DHRS9) expression with clinicopathological features. Survival curves were created applying the Kaplan-Meier method, and the log-rank test was conducted to compare prognostic utility between high and low DHRS9 expression groups. Multivariate Cox proportional hazards regression analysis was applied to identify independent prognostic biomarkers based on variables with prognostic utility at the univariate level.Results: Utilizing a public transcriptome dataset, we identified that the DHRS9 gene is the most considerably upregulated gene related to epithelial cell differentiation (GO: 0030855) among rectal cancer patients with CCRT resistance. Employing immunohistochemical staining, we also demonstrated that high DHRS9 immunoexpression is considerably associated with an aggressive clinical course and CCRT resistance in our rectal cancer cohort. Among all variables with prognostic utility at the univariate level, only high DHRS9 immunoexpression was independently unfavorably prognostic of all three endpoints (all p <= 0.048) in the multivariate analysis. In addition, applying bioinformatic analysis, we also linked DHRS9 with unrevealed functions, such as keratan sulfate and mucin synthesis which may be implicated in CCRT resistance.Conclusion: Altogether, DHRS9 expression may serve as a helpful predictive and prognostic biomarker and assist decision-making for rectal cancer patients who underwent neoadjuvant CCRT.
    Relation: PATHOLOGY & ONCOLOGY RESEARCH, v.28, Article 1610537
    Appears in Collections:[Dept. of Pharmacy] Periodical Articles
    [Dept. of Cosmetic Science and institute of cosmetic science] Periodical Articles

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