ArticleAging2024
HOXC9 characterizes a suppressive tumor immune microenvironment and integration with multiple immune biomarkers predicts response to PD-1 blockade plus chemotherapy in lung adenocarcinoma.
Article in Aging, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 4 citations in OpenAlex.
- LAMTOR5 drives glioblastoma progression via activation of the HOXC9/YTHDF2 positive feedback loop.The Journal of biological chemistry · 2026Article
- Multi-omics profiling of recurrence-associated extrachromosomal circular DNA characteristics and its prognostic potential in lung adenocarcinoma.Precision clinical medicine · 2026Article
- HOXC9 promotes cell proliferation and suppresses mitochondria-dependent apoptosis through the AKT/mTOR pathway in esophageal squamous cell carcinoma.Molecular and cellular biochemistry · 2026Article
- HOXC9 accelerates esophageal squamous cell carcinoma progression via OTUD1-FABP5-mediated lipid metabolic reprogramming.Cell death & disease · 2026Article
- Review
- Immunosenescence shapes the tumor immune microenvironment and limits PD-1/PD-L1 blockade efficacy in older patients with cancer.Frontiers in immunology · 2026Review
- Integrative multi-omics analysis decodes HOXC9-driven malignant transformation and metastasis in OSCC.iScience · 2025Article
- Biomarkers and ImmuneScores in lung cancer: predictive insights for immunotherapy and combination treatment strategies.Biological procedures online · 2025Review
- Integrated machine learning analysis of 30 cell death patterns identifies a novel prognostic signature in glioma.Frontiers in cell and developmental biology · 2025Article
- Integrated Analysis Reveals COL4A3 as a Novel Diagnostic and Therapeutic Target in UV-Related Skin Cutaneous Melanoma.Clinical, cosmetic and investigational dermatology · 2024Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe quest for dependable biomarkers to predict responses to immune checkpoint inhibitors (ICIs) combined with chemotherapy in advanced non-small cell lung cancer remains unfulfilled. HOXC9, known for its role in oncogenesis and creating a suppressive tumor microenvironment (TME), shows promise in enhancing predictive precision when included as a TME biomarker. This study explores the predictive significance of HOXC9 for ICI plus chemotherapy efficacy in lung adenocarcinoma (LUAD).
methodsFollowing the bioinformatic findings, assays were performed to ascertain the effects of Hoxc9 on oncogenesis and response to programmed death 1 (PD-1) blockade. Furthermore, a cohort of LUAD patients were prospectively enrolled to receive anti-PD-1 plus chemotherapy. Based on the expression levels, baseline characteristics, and clinical outcomes, the predictive potential of HOXC9, PD-L1, CD4, CD8, CD68, and FOXP3 was integrally analyzed. HOXC9 not only mediated oncogenesis, but also corelated with suppressive TME. CMT167 and LLC cell lines unveiled the impacts of Hoxc9 on proliferation, invasion, and migration. Subsequently, tumor-bearing murine models were established to validate the inverse relationship between Hoxc9 expression and effective CD8+ T cells.
resultsInhibition of Hoxc9 significantly curtailed tumor growth (P<0.05), independent of PD-1 blockade. In patient studies, while individual markers fell short in prognosticating survival, a notable elevation in CD8-positive expression was observed in responders (P=0.042). Yet, the amalgamation of HOXC9 with other markers provided a more distinct differentiation between responders and non-responders. Notably, patients displaying PD-L1+/HOXC9- and CD8+/HOXC9- phenotypes exhibited significantly prolonged progression-free survival.
conclusionsThe expression of HOXC9 may serve as a biomarker to amplifying predictive efficacy for ICIs plus chemotherapy, which is also a viable oncogene and therapeutic target for immunotherapy in LUAD.
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