Evidence map›Paper›PMID 41367585›Full record

ArticleTranslational lung cancer research2025

A public data-based molecular classification of small cell lung cancer by neuroactive signaling networks unveils distinct microenvironment landscapes and immunotherapy-related prognostic biomarkers.

Wensheng Zhou, Yujie Tang, Jiyuan Zeng, Xiaoyi Zhang, Haotian Meng, Wenhui Guan, Yue Zhu, Huixin Jiang, Yansheng Wang, Xiaohong Xie and 2 more

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Article in Translational lung cancer research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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12 authors.

Wensheng Zhou *State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.ORCID https://orcid.org/0000-0002-5002-8445
Yujie Tang *State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Jiyuan ZengState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Xiaoyi ZhangState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Haotian MengState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Wenhui GuanState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Yue ZhuState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Huixin JiangState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Yansheng WangState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Xiaohong XieState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Chengzhi ZhouState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Ming LiuState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Small cell lung cancer (SCLC) represents an aggressive malignancy characterized by marked heterogeneity and neuroendocrine differentiation. Despite its clinical significance, the functional landscape of neuroendocrine function, while neuroactive-signaling-related genes (NRGs) in SCLC pathogenesis remains poorly characterized. Therefore, the aim of this study is to classify SCLC based on neuroactive signaling networks and to analyze the characteristics of these classifications in relation to the immune microenvironment. Methods: Through integrated analysis of bulk transcriptomic profiling from 79 primary SCLC tumors and single-cell transcriptomic profiling from 11 SCLC tumors, we employed a consensus clustering algorithm to deconvolute transcriptional programs underlying neuroactive signaling networks. Molecular functions and tumor-infiltrated immune cells were estimated from bulk transcriptomes using bioinformatics methods. Single-cell transcriptomic analysis was implemented for cross-validation and cellular characterization. Results: Bulk-seq analyses reported that the transcriptional variability of three major clusters of tumors were associated with different clinical outcomes and biological pathways. Clinical, genomic, and immunological characteristics were observed among three clusters. Furthermore, the key genes module of cluster with the worst survival were identified as neuroactive-signaling-related signature (NRS) and used to classify tumor samples into two distinct intra-tumoral subtypes (H-NRS and L-NRS) with single-cell transcriptomic data. At single-cell level, malignant cells in H-NRS tumor were in later cell state and had more frequent cellular communication. And NRS subsequently was identified as a biomarker correlated with better prognosis for patients receiving chemoimmunotherapy. It was found that Natriuretic Peptide C (NPPC), as one of the key genes in NRS, was overexpressed in SCLC tumor cells and correlated with poor prognosis. Treatment with C-type natriuretic peptide (CNP) facilitates cellular migration and metastatic potential. Conclusions: This study proposes a novel molecular taxonomy for SCLC grounded in neuroactive signaling networks, suggests a potential prognostic biomarker to aid in therapeutic stratification, and identifies NPPC as a candidate therapeutic target worthy of further investigation in metastatic SCLC. Our findings may help bridge gaps in understanding between neuroendocrine biology and tumor microenvironment (TME) dynamics during SCLC evolution.

Indexed as

immunotherapyNeuroactive signalingtumor microenvironment (TME)

Identifiers

PMID41367585
PMCPMC12683401

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