image: (A) Principal component analysis (PCA) of lymphocyte subsets and factors such as age in Control, LC, and LC-PTB groups, and the joint analysis of LC & LC-PTB. PC1 and PC2 represent the first and second principal components, respectively, with the percentages in parentheses indicating the variance contribution of each. (B) Pearson correlation analysis of absolute lymphocyte subset counts in LC and LC-PTB populations. The correlation coefficient ranges from 0 to 1, with values closer to 1 indicating stronger correlations. Statistical significance is indicated as follows: *: P<0.05; **: P<0.01; ***: P<0.001; ****: P<0.0001. (C) Analysis of absolute counts and positivity rates of lymphocyte subsets among Control, LC, and LC-PTB groups. Green, yellow, and red represent absolute lymphocyte counts, while blue represents lymphocyte subset positivity rates. Only statistically significant comparisons are indicated; non-significant differences are not marked to avoid visual congestion.
Credit: Ling Yang
Coexisting lung cancer and pulmonary tuberculosis (LC-PTB) is clinically challenging in diagnosis and treatment, and its mechanisms are unclear. This study aimed to explore its immune and molecular basis to identify diagnostic biomarkers. We prospectively enrolled LC patients, LC-PTB patients, and controls. Lymphocyte subsets were analyzed by flow cytometry. Key markers were identified through blood transcriptome sequencing and bioinformatics (differential expression, GSEA, GO/KEGG), and validated by RT-qPCR and immunohistochemistry. Analysis included 138 subjects (50 controls, 50 LC, 38 LC-PTB). Compared to LC alone, LC-PTB demonstrated significantly increased CD4+ T cells (p = 0.0064) and NK cells (p = 0.0447), with an elevated CD4/CD8 ratio. Transcriptome analysis identified 144 upregulated and 435 downregulated genes in LC-PTB versus controls, and 216 upregulated and 388 downregulated genes versus LC alone (|Fold Change| ≥ 2, p < 0.05). Enrichment analysis revealed involvement of antigen presentation, oxidative phosphorylation, and nitrogen metabolism. Six key genes (ANK2, EPB42, CA1, HBB, HBD, MYL4) were identified. A four-gene model (CA1, HBD, MYL4, ANK2) discriminated LC-PTB from LC (AUC 0.940, 95% CI 0.846–1.000). We provide the first immune-transcriptomic map of LC-PTB and a validated four-gene diagnostic signature ready for external evaluation.
Method of Research
Experimental study
Subject of Research
Human tissue samples
Article Title
Immunometabolic Features and Key Biomarkers in Lung Cancer Complicated by Pulmonary Tuberculosis: Insights from Transcriptome and Clinical Cohort Analysis
Article Publication Date
26-Nov-2025
COI Statement
The authors declare that they have no competing interests.