TCL1 as a hub protein associated with the PI3K/AKT signaling pathway in diffuse large B-cell lymphoma based on proteomics methods.

Abstract

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.

• Authors: Hai-Xia Gao, Si-Jing Li, Jing Niu, Zhi-Ping Ma, Aijiang Nuerlan, Jing Xue, Meng-Bo Wang, Wen-Li Cui, Gulinaer Abulajiang, Wei Sang, Wei Zhang, Xin-Xia Li
• Journal: Pathology, research and practice (Pathol Res Pract) Vol. 216 Issue 2 Pg. 152799 (Feb 2020) ISSN: 1618-0631 [Electronic] Germany
• PMID: 31932115 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier GmbH. All rights reserved.

Chemical References

• Biomarkers, Tumor
• TCL1A protein, human
• Proto-Oncogene Proteins c-akt

Topics

• B-Lymphocytes (metabolism, pathology)
• Biomarkers, Tumor (metabolism)
• Cohort Studies
• Female
• Humans
• Immunohistochemistry
• Lymphoma, Large B-Cell, Diffuse (diagnosis, metabolism, pathology)
• Male
• Middle Aged
• Phosphatidylinositol 3-Kinases (metabolism)
• Prognosis
• Proteomics
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction