Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, No. 137 Liyushan Southern Road, Urumqi, the Xinjiang Uygur Autonomous Region of China, 830054, PR China; Xinjiang Medical University, No. 393 Xinyi Road, Urumqi, the Xinjiang Uygur Autonomous Region of China, 830011, PR China.
Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, No. 137 Liyushan Southern Road, Urumqi, the Xinjiang Uygur Autonomous Region of China, 830054, PR China.
Pathol Res Pract. 2020 Feb;216(2):152799. doi: 10.1016/j.prp.2019.152799. Epub 2020 Jan 7.
This study aimed to investigate the hub protein related to the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in diffuse large B-cell lymphoma (DLBCL). We used proteomics methods (iTRAQ) to explore the differentially expressed proteins in the non-germinal center B-cell -like (non-GCB) DLBCL in our previous study. In this study, a total of 137 formalin-fixed paraffin-embedded DLBCL tissue samples were analyzed via immunohistochemistry to verify the expression of TCL1, AKT1 + 2+3, IKKβ and to determine the differentially expressed proteins associated with the PI3K/AKT signaling pathway. Spearman correlation was used to analyze the relationship between these proteins, and survival analysis was used to investigate their effects on prognosis. Immunohistochemistry analysis indicated that TCL1, AKT1 + 2+3, and IKKβ were highly positively expressed in DLBCL. Results showed that the expression of TCL1 was related to ethnicity (p = 0.022), primary site (p = 0.045), Ann Arbor stage (p = 0.037), the International Prognostic Index (p = 0.005), β2-microglobulin (p = 0.030), BCL2 expression (p < 0.001), and Ki-67 expression (p = 0.008). A positive correlation was found between TCL1 and AKT1 + 2+3 (p < 0.001; r = 0.475). A positive correlation was also found between AKT1 + 2+3 and IKKβ (p < 0.001; r = 0.342). In survival analysis, anemia, non-treatment with R‑CHOP, positive TCL1 expression, and Ki-67 expression≥50% independently predicted short progression-free survival and overall survival in the total cohort (p < 0.05). Thus, TCL1 as a hub protein is associated with the PI3K/AKT signaling pathway in DLBCL. TCL1 expression indicated a poor prognosis in patients with DLBCL. With further studies, TCL1 may be established as a reliable prognostic biomarker and potential immunotherapeutic target for improving therapeutic efficacy for DLBCL in the future.
这项研究旨在探讨磷脂酰肌醇 3-激酶（PI3K）/蛋白激酶 B（AKT）信号通路相关的枢纽蛋白在弥漫性大 B 细胞淋巴瘤（DLBCL）中的作用。我们之前的研究采用蛋白质组学方法（iTRAQ）来探索非生发中心 B 细胞样（non-GCB）DLBCL 中的差异表达蛋白。在这项研究中，我们通过免疫组织化学分析了总共 137 例福尔马林固定石蜡包埋的 DLBCL 组织样本，以验证 TCL1、AKT1+2+3、IKKβ的表达，并确定与 PI3K/AKT 信号通路相关的差异表达蛋白。采用 Spearman 相关性分析这些蛋白之间的关系，并进行生存分析以探讨它们对预后的影响。免疫组织化学分析表明，TCL1、AKT1+2+3 和 IKKβ在 DLBCL 中高度过表达。结果显示，TCL1 的表达与种族（p=0.022）、原发部位（p=0.045）、Ann Arbor 分期（p=0.037）、国际预后指数（p=0.005）、β2-微球蛋白（p=0.030）、BCL2 表达（p＜0.001）和 Ki-67 表达（p=0.008）有关。TCL1 与 AKT1+2+3 之间存在正相关关系（p＜0.001；r=0.475）。AKT1+2+3 与 IKKβ 之间也存在正相关关系（p＜0.001；r=0.342）。在生存分析中，贫血、未接受 R-CHOP 治疗、TCL1 阳性表达和 Ki-67 表达≥50%独立预测总队列的无进展生存期和总生存期较短（p＜0.05）。因此，TCL1 作为枢纽蛋白与 DLBCL 中的 PI3K/AKT 信号通路有关。TCL1 表达提示 DLBCL 患者预后不良。随着进一步的研究，TCL1 可能被确立为一种可靠的预后生物标志物和潜在的免疫治疗靶点，以提高未来 DLBCL 的治疗效果。
