Page 132 - ITPS-7-3

INNOSC Theranostics and
Pharmacological Sciences Prognostic values of peripheral blood CD4T transcriptomic signature

significantly related to clinical response. The near-perfect Consent for publication
stratification of diseased subjects here is consistent with
the prior knowledge that CD4T abundance is essential to Not applicable.
a favorable prognosis of anti-retroviral treatment response Availability of data
in HIV-1 patients. In addition, formal statistical testing
1,2
revealed a significant association between the gene As described in the Materials and Methods section, the
signature and anti-retroviral response. This observed datasets and code used in this study can be publicly accessed
effect remained consistent in direction and significant through Gene Expression Omnibus and GitHub, respectively.
statistically after accounting for clinical covariates. Taken
together, these results support the generalizability of References
CD4T abundance-based gene signature, identified in the 1. Swain SL, McKinstry KK, Strutt TM. Expanding roles for
healthy context, to the diseased context, and reinforce the CD4+ T cells in immunity to viruses. Nat Rev Immunol.
centrality of CD4T-based immune modulation during 2012;12(2):136-148.
HIV-1 pathogenesis. doi: 10.1038/nri3152
Several limitations of this study should be 2. Vidya Vijayan KK, Karthigeyan KP, Tripathi SP, Hanna LE.
acknowledged. First, despite having high-quality gene- Pathophysiology of CD4+ T-cell depletion in HIV-1 and
expression data, the application population used for HIV-2 Infections. Front Immunol. 2017;8:580.
biological and clinical inference is small. In particular, doi: 10.3389/fimmu.2017.00580
the LASSO model performance might improve if model 3. Woelk CH, Beliakova-Bethell N, Goicoechea M, et al. Gene
training was conducted in a sex-stratified manner, a expression before HAART initiation predicts HIV-infected
known risk-modifying factor in HIV/AIDS. Due to individuals at risk of poor CD4+ T-cell recovery. AIDS.
15
the limited training sample size, model development on 2010;24(2):217-222.
sex-stratified data was unlikely empowered to achieve
robust performance. Second, there were variations in the doi: 10.1097/QAD.0b013e328334f1f0
study designs, and many clinical variables of the study 4. Coelho AVC, Gratton R, de Melo JPB, et al. HIV-1 Infection
populations used were not consistently collected or transcriptomics: Meta-analysis of CD4+ T cells gene
reported. Importantly, the gene-signature identification expression profiles. Viruses. 2021;13(2):244.
process leverages only gene expression without clinical doi: 10.3390/v13020244
covariates such as subject age and race. Finally, a broader 5. Zannas AS, Jia M, Hafner K, et al. Epigenetic upregulation
limitation is the availability of datasets and samples of FKBP5 by aging and stress contributes to NF-κB-driven
with high consistency (i.e., low heterogeneity). Future inflammation and cardiovascular risk. Proc Natl Acad Sci U
confirmatory and follow-up studies with comprehensive S A. 2019;116(23):11370-11379.
and robust designs will be crucial to the understanding doi: 10.1073/pnas.1816847116
of the molecular mechanisms of diseases related to CD4T
abundance. 6. Chen Y. A cancer proliferation gene signature supervised
by Ki-67 strata specific to luminal A, estrogen receptor-
Acknowledgments positive, and HER2-negative ductal carcinomas. Med Res
Arch. 2022;10(10).
The author would like to thank the anonymous peer-
reviewers and the journal editorial team for their input. doi: 10.18103/mra.v10i10.3160
7. Chen Y. Transcriptomic profiling of subcutaneous adipose
Funding tissue in relation to bariatric surgery: A retrospective,
pooled re-analysis. J Obes Metab Syndr. 2023;32(1):98-102.
None.
doi: 10.7570/jomes22065
Conflict of interest 8. Chen Y. Pooled microarray expression analysis of failing
The author declares no competing interests. left ventricles reveals extensive cellular-level dysregulation
independent of age and sex. J Mol Cell Cardiol Plus.
Author contributions 2024;7:100060.
This is a single-authored article. doi: 10.1016/j.jmccpl.2023.100060
9. Tibshirani R. Regression selection and shrinkage via the
Ethics approval and consent to participate lasso. J R Stat Soc B. 1996;58(1):267-288.
Not applicable. doi: 10.2307/2346178

Volume 7 Issue 3 (2024) 6 doi: 10.36922/itps.2761