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Abstract：
Background: Aggressive mature T-cell lymphoma (TCL) is a disease that carries a poor prognosis. Methods: We analyzed the expression of 22 tumor cell functional proteins in 16 randomly selected patients with TCL. Immunohistochemistry was performed in paraffin-embedded tumor tissue sections to determine the protein expression statuses in tumor cells. Results: Glucose-regulated protein 94 (GRP94), a protein that serves as a pro-survival component under endoplasmic reticulum (ER) stress in the tumor microenvironment, was significantly associated with a shortened survival. Furthermore, significant differences were observed when GRP94 was combined with six other factors. The six factors were (1) programmed cell death-ligand 1 (PD-L1); (2) programmed cell death 1 (PD-1); (3) aldo-keto reductase family 1 member C3 (AKR1C3); (4) P53, a tumor suppressor; (5) glucose-regulated protein 78 (GRP78), an ER stress protein; and (6) thymidine phosphorylase (TP). Based on the combination of GRP94 and the six other factors expressed in the tumors, we propose a new prognostic classification system for TCL (TCL Urayasu classification). Group 1 (relatively good prognosis): GRP94-negative (n = 6; median OS, 88 months; p < 0.01); Group 2 (poor prognosis): GRP94-positive, plus expression of two of the six factors mentioned above (n = 5; median OS, 25 months; p > 0.05); and Group 3 (very poor prognosis): GRP94-positive, plus expression of at least three of the six factors mentioned above (n = 5; median OS, 10 months; p < 0.01). Conclusions: Thus, the TCL Urayasu prognostic classification may be a simple, useful, and innovative classification that also explains the mechanism of resistance to treatment for each functional protein. If validated in a larger number of patients, the TCL Urayasu classification will enable a targeted treatment using selected inhibitors acting on the abnormal protein found in each patient.
摘要：
背景：侵袭性成熟T细胞淋巴瘤（TCL）是一种预后不良的疾病。方法：我们分析了16例随机选择的TCL患者中22种肿瘤细胞功能蛋白的表达。在石蜡包埋的肿瘤组织切片中进行免疫组织化学以确定肿瘤细胞中的蛋白质表达状态。结果：葡萄糖调节蛋白94（GRP94），一种在肿瘤微环境中内质网（ER）应激下充当促生存成分的蛋白质，与生存期缩短显著相关。此外，当GRP94与其他6个因素结合时,观察到显著差异.六个因素是（1）程序性细胞死亡配体1（PD-L1）；（2）程序性细胞死亡1（PD-1）；（3）醛酮还原酶家族1成员C3（AKR1C3）；（4）肿瘤抑制因子P53；（5）葡萄糖调节蛋白78（GRP78），ER应激蛋白;和(6)胸苷磷酸化酶(TP)。基于GRP94和其他六种在肿瘤中表达的因子的组合，我们提出了一种新的TCL预后分类系统(TCLUrayasu分类)。第1组（预后相对良好）：GRP94阴性（n=6；中位OS，88个月；p<0.01）；第2组（预后不良）：GRP94阳性，加上上述六个因素中的两个因素的表达(n=5；中位OS，25个月；p>0.05）；第3组（预后极差）：GRP94阳性，加上上述六个因素中至少三个的表达(n=5；中位OS，10个月；p<0.01）。结论：因此，TCLUrayasu预后分类可能是一个简单的，有用的,以及创新的分类，这也解释了每种功能蛋白对治疗的抗性机制。如果在更多的患者中验证，TCLUrayasu分类将能够使用选定的抑制剂对每位患者中发现的异常蛋白进行靶向治疗.
