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    標題: High SLC28A2 expression endows an inferior survival for rectal cancer patients managed by neoadjuvant CCRT
    作者: Chen, Hsin-Pao
    Chen, Chih-, I
    Liu, Kuang-Wen
    Chen, Tzu-Ju
    Tian, Yu-Feng
    Kuo, Yu-Hsuan
    Li, Wan -Shan
    Tsai, Hsin-Hwa
    Wu, Li-Ching
    Yeh, Cheng-Fa
    Li, Chien-Feng
    Chou, Chia-Lin
    Lai, Hong-Yue
    貢獻者: E-Da Hospital
    I Shou University
    E-Da Hospital
    I Shou University
    I Shou University
    Chi Mei Hospital
    Chung Hua University
    National Sun Yat Sen University
    Chi Mei Hospital
    Chi Mei Hospital
    Chia Nan University of Pharmacy & Science
    Chi Mei Hospital
    Chi Mei Hospital
    Chi Mei Hospital
    Chi Mei Hospital
    Chia Nan University of Pharmacy & Science
    National Health Research Institutes - Taiwan
    China Medical University Taiwan
    關鍵字: chemoradiotherapy
    fluorouracil
    日期: 2022
    上傳時間: 2023-12-11 14:04:47 (UTC+8)
    出版者: ELSEVIER GMBH
    摘要: For rectal cancer patients with stage T3-4 disease or positive lymph node, neoadjuvant concurrent chemo-radiotherapy (CCRT) has become the standard treatment, but the clinical outcomes are still far from satisfactory. Accordingly, a more precise predictive tool such as genetic biomarkers is urgently required to optimize therapy decisions. Colorectal cancer (CRC) development has been considerably correlated with cellular metabolic process involving nucleotides, but the underlying molecular mechanisms remain unclear. In this study, we employed a transcriptome dataset comprising 46 rectal adenocarcinoma patients undergoing preoperative CCRT and focused on nucleobase-containing compound metabolic process (GO: 0055134) for data mining. We identified solute carrier family 28 member 2 (SLC28A2) as the most considerably upregulated gene among rectal cancer patients with CCRT resistance. Afterwards, there were a total of 172 rectal cancer tissue blocks procuring from our biobank, and the immunointensity of SLC28A2 was appraised utilizing immunohistochemical staining. Strong SLC28A2 immunointensity was significantly linked to female patients (p = 0.032), vascular invasion (p = 0.021), and post-CCRT tumor invasion and regional lymph node involvement (p < 0.001 and p = 0.005). Notably, pa-tients with strong SLC28A2 immunointensity had no tumor downstaging (p < 0.001). Univariate analysis revealed that high SLC28A2 immunoexpression was considerably unfavorably linked to all three endpoints: local recurrence-free survival (LRFS), metastasis-free survival (MeFS), and disease-specific survival (DSS) (all p < 0.0333). Moreover, both high SLC28A2 immunoexpression and low tumor regression grade were independently unfavorable prognostic factors for all three endpoints (all p < 0.013) in the multivariate analysis. Utilizing function prediction analysis, SLC28A2 upregulation was more likely to be linked with stem cell homeostasis in rectal cancer. In brief, we demonstrated that high SLC28A2 immunoexpression is substantially linked to an advanced stage, poor response to CCRT, and worse patient survival. Consequently, SLC28A2 expression can be a valuable predictive and prognostic marker for rectal cancer patients and be an encouraging therapeutic target for those with CCRT resistance.
    關聯: PATHOLOGY RESEARCH AND PRACTICE, v.239, n.CB2, pp.CC2, pp.-,
    顯示於類別:[行政單位] 123

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