Immune infiltration and drug specificity analysis of different subtypes based on functional status in angioimmunoblastic T-cell lymphoma

Shicong Zhu; Yan Zhao; Cheng Xing; Wancheng Guo; Zineng Huang; Huifang Zhang; Le Yin; Xueqin Ruan; Heng Li; Zhao Cheng; Zhihua Wang; Hongling Peng

doi:10.1016/j.heliyon.2023.e18836

Immune infiltration and drug specificity analysis of different subtypes based on functional status in angioimmunoblastic T-cell lymphoma

Heliyon. 2023 Aug 1;9(8):e18836. doi: 10.1016/j.heliyon.2023.e18836. eCollection 2023 Aug.

Authors

Shicong Zhu¹, Yan Zhao^{2

3}, Cheng Xing^{2

3}, Wancheng Guo^{2

3}, Zineng Huang^{2

3}, Huifang Zhang^{2

3}, Le Yin^{2

3}, Xueqin Ruan^{2

3}, Heng Li^{2

3}, Zhao Cheng^{2

3}, Zhihua Wang^{2

3}, Hongling Peng^{2

3

4}

Affiliations

¹ Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
² Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
³ Institute of Molecular Hematology, Central South University, Changsha, Hunan, China.
⁴ Hunan Engineering Research Center of Cell Immunotherapy for Hematopoietic Malignancies, Changsha, Hunan 410011, China.

Abstract

Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma (PTCL) strongly correlated with worse clinical outcomes. However, the role of characteristic pathway-related genes in patients with AITL (e.g., subtype typing and pathogenesis) remains unknown. In this study, we intended to understand the potential role and prognostic value of characteristic pathways in AITL and identified a model for subtype identification based on pathway-related functional status. Transcriptomic (RNA-seq) data were obtained from the Gene Expression Omnibus database for three sets of tumor tissues from AITL patients. AITL was divided into three clusters based on the pathway profile of patients and the best clustering k = 3, and differentially expressed genes (DEGs) in the three clusters were analyzed. The top 45 important variables associated with characteristic pathways, such as Huntington's disease, VEGF signaling pathway, nucleotide excision repair, ubiquitin-mediated proteolysis, purine metabolism, olfactory transduction, etc., were used to construct a subtype identification model. The model was experimentally validated and proved to possess good predictive efficacy. In addition, pathway-related subtype typing was significantly associated with different immune cell infiltration in AITL. Further analysis revealed that the drug IC₅₀ values predicted also differed markedly among the different subtypes, thus further identifying some subtype-specific drugs. Our study indicates a potential role of characteristic pathways in AITL staging for the first time, provides novel insights for future research targeting AITL, and points to potential therapeutic options for patients with different subtypes of AITL.

Keywords: Angioimmunoblastic T-cell lymphoma; Immune infiltration; Pathways; Specific drugs; Subtype typing model.