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Abstract：
BACKGROUND Gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) is the most common histological subtype of extra-nodal DLBCL, but the risk factors, prognostic biomarkers, histopathological classifications, and treatment strategies have not had significant progress. Emerging evidence shows that cystatin SN (CST1) is involved in tumor progression in several cancer types, but its role in GI-DLBCL has not been revealed. MATERIAL AND METHODS We established a cohort consisting of 84 patients with GI-DLBCL who underwent surgical resection. The expression of CST1 in the cohort was investigated by immunohistochemistry, which divided the patients into subgroups with low or high expression of CST1. Moreover, the CST1 expression in GI-DLBCL tissues or adjacent GI tissues were compared with RT-qPCR. The correlation between CST1 expression and clinicopathological factors was analyzed with the chi-square test. The prognostic significance of CST1 was estimated by univariate and multivariate analysis, and statistical significance was analyzed with the log-rank test. RESULTS CST1 was aberrantly upregulated in GI-DLBCL tissues compared with in non-tumor GI tissues. High expression of CST1 indicated poor prognosis of GI-DLBCL (P=0.012), and CST1 can be regarded as an independent prognostic biomarker of GI-DLBCL (hazard ratio=3.07). In our study, serum lactate dehydrogenase (P=0.002), performance status (P=0.003), Lugano stage (P=0.002), and International Prognostic Index (P=0.001) were also prognostic factors of GI-DLBCL. CONCLUSIONS CST1 is an independent prognostic biomarker of GI-DLBCL, indicating unfavorable prognosis. Our results suggested that CST1 detection can be a promising method to stratify high-risk patients and guide individual treatment.
摘要：
背景胃肠道弥漫性大B细胞淋巴瘤(GI-DLBCL)是结外DLBCL最常见的组织学亚型,但是风险因素，预后生物标志物，组织病理学分类，和治疗策略没有取得重大进展。新的证据表明，胱抑素SN（CST1）参与几种癌症类型的肿瘤进展，但其在GI-DLBCL中的作用尚未揭示。材料和方法我们建立了一个由84例接受手术切除的GI-DLBCL患者组成的队列。通过免疫组织化学研究队列中CST1的表达，将患者分为CST1低表达或高表达的亚组。此外，用RT-qPCR方法比较CST1在GI-DLBCL组织或邻近GI组织中的表达。采用卡方检验分析CST1表达与临床病理因素的相关性。通过单因素和多因素分析估计CST1的预后意义，采用对数秩检验进行统计学分析。结果与非肿瘤GI组织相比，GI-DLBCL组织中CST1异常上调。CST1高表达提示GI-DLBCL预后不良(P=0.012),和CST1可被视为GI-DLBCL的独立预后生物标志物(风险比=3.07)。在我们的研究中,血清乳酸脱氢酶（P=0.002），性能状态（P=0.003），卢加诺阶段（P=0.002），国际预后指数（P=0.001）也是GI-DLBCL的预后因素。结论CST1是GI-DLBCL的独立预后生物标志物，提示预后不良。我们的结果表明，CST1检测可以成为对高危患者进行分层和指导个体化治疗的一种有前途的方法。
