ArticleInternational journal of biological sciences2022
Integrated pathological analysis to develop a Gal-9 based immune survival stratification to predict the outcome of lung large cell neuroendocrine carcinoma and its usefulness in immunotherapy.
Article in International journal of biological sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 4 citations in OpenAlex.
- Review
- Galectin-9-An Emerging Glyco-Immune Checkpoint Target for Cancer Therapy.International journal of molecular sciences · 2025Review
- A case-based review of urachal carcinoma with mixed small cell neuroendocrine and adenocarcinoma components, with one new case report and analysis of nine published cases.Frontiers in endocrinology · 2025Review
- Galectin-9 in cancer therapy: from immune checkpoint ligand to promising therapeutic target.Frontiers in cell and developmental biology · 2023Review
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study aimed to integrate the cell spatial organization to develop a Gal-9-based immune survival stratification in the lung large cell neuroendocrine carcinoma (LCNEC) and investigate its potentials to immunotherapy. The expression of Gal-9 and other twelve immune markers were evaluated in 122 cases of surgical LCNEC samples from our center using immunohistochemistry. The Gal-9-based immune survival stratification risk score was constructed and its predictive performance was evaluated. Then, we thoroughly explored the effects of Gal-9 and immune risk score on LCNEC immune pathways, immune micro-environment and immunotherapy sensitivity in different cohort and platform, and made a validation in pathology images using Histology-based Digital-Staining (HDS). In 122 LCNEC samples, 43 cases were positive Gal-9 expression on tumor cells (Gal-9 TC). Increased Gal-9 TC predicted worse overall survival. Gal-9's interaction with other immune markers added to the immune suppression and immune tolerance in LCNEC. Immune protein marker-based risk score consisting of Gal-9, CD3, CD4, PD-L1, and PD-1 was developed and validated to robustly discriminate survival high-risk or low-risk in LCNEC patients. The high-risk group characterized by immune-desert tumor had less various T cells. The low-risk group featuring immune-inflamed tumor was more likely to respond to anti-PD1 immunotherapy. HDS in 122 LCNEC samples' 108,369 cells validated that the high-risk group had more tumor cells, less stromal cells, less lymphocytes, higher tumor cell nucleic solidity and lower stromal cells nucleic solidity. An integrated pathological analysis confirms the Gal-9 based immune survival stratification is distinctively related to micro-environment status involved in immune suppression and immune tolerance and could act as a combinatorial biomarker to predict the outcome of LCNEC. These findings may help effectively stratify LCNEC patients sensitive to immunotherapy.
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