WNT7A correlates with immunosuppression and predicts adverse prognosis in lung adenocarcinoma: Potential implication of the NF-kappaB/CCL2 Axis

(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)

By: Xiang Guo · Zhengfang Xiao · Yao Zhang · Li Wang · Hui Hu · Ting Liu · Yingjun Kong

7 April 2026 at 18:00

Cytokine. 2026 Apr 6;202:157144. doi: 10.1016/j.cyto.2026.157144. Online ahead of print.

ABSTRACT

BACKGROUND: The remodeling of the tumor immune microenvironment (TME) is a pivotal determinant of therapeutic efficacy and clinical outcome in Lung Adenocarcinoma (LUAD). While WNT signaling is a known oncogenic driver, the specific immunomodulatory role of WNT7A and its potential crosstalk with inflammatory pathways in LUAD remain to be fully elucidated. We sought to define the prognostic value of WNT7A and explore the molecular mechanisms by which it may foster an immunosuppressive TME.

METHODS: We performed a multi-omics analysis utilizing the TCGA-LUAD cohort (N = 508) and validated findings in an independent external cohort (GSE30219, N = 293). The prognostic significance of WNT7A was evaluated using Kaplan-Meier and multivariate Cox regression analyses. TME composition was dissected via ssGSEA, focusing on myeloid-derived suppressor cell (MDSC) infiltration. Mechanistic pathways were identified using Gene Set Enrichment Analysis (GSEA) and gene co-expression networks.

RESULTS: High WNT7A expression was identified as a significant predictor of poor Overall Survival (OS) in the TCGA cohort (P < 0.05) and validated in the external cohort (P < 0.05). Multivariate analysis confirmed WNT7A as an independent prognostic risk factor (HR = 1.085, P = 0.036). Immunologically, WNT7A expression was positively correlated with MDSC infiltration (R = 0.43, P < 0.001), suggesting a shift towards an immune-tolerant phenotype. Mechanistically, GSEA revealed a robust activation of inflammatory signaling in the high-WNT7A group. Specifically, the TNFA Signaling via NF-κB pathway was significantly enriched(NES = 2.52, P < 0.001). Consistent with this pathway activation, WNT7A showed a statistically significant positive correlation with CCL2 (P < 0.001), a critical chemokine for MDSC recruitment, implicating the NF-κB/CCL2 axis in this process.

CONCLUSION: WNT7A serves as a prognostic biomarker linked to immune evasion in LUAD, potentially by modulating the NF-κB/CCL2/MDSC axis. This study identifies WNT7A as a potential therapeutic target to remodel the immune microenvironment, providing a rationale for future investigations into WNT-targeted strategies to improve immunotherapy efficacy.

PMID:41946008 | DOI:10.1016/j.cyto.2026.157144

WNT7A correlates with immunosuppression and predicts adverse prognosis in lung adenocarcinoma: Potential implication of the NF-kappaB/CCL2 Axis

Omics In Lung

By: Xiang Guo · Zhengfang Xiao · Yao Zhang · Li Wang · Hui Hu · Ting Liu · Yingjun Kong

7 April 2026 at 18:00

Cytokine. 2026 Apr 6;202:157144. doi: 10.1016/j.cyto.2026.157144. Online ahead of print.

ABSTRACT

BACKGROUND: The remodeling of the tumor immune microenvironment (TME) is a pivotal determinant of therapeutic efficacy and clinical outcome in Lung Adenocarcinoma (LUAD). While WNT signaling is a known oncogenic driver, the specific immunomodulatory role of WNT7A and its potential crosstalk with inflammatory pathways in LUAD remain to be fully elucidated. We sought to define the prognostic value of WNT7A and explore the molecular mechanisms by which it may foster an immunosuppressive TME.

METHODS: We performed a multi-omics analysis utilizing the TCGA-LUAD cohort (N = 508) and validated findings in an independent external cohort (GSE30219, N = 293). The prognostic significance of WNT7A was evaluated using Kaplan-Meier and multivariate Cox regression analyses. TME composition was dissected via ssGSEA, focusing on myeloid-derived suppressor cell (MDSC) infiltration. Mechanistic pathways were identified using Gene Set Enrichment Analysis (GSEA) and gene co-expression networks.

RESULTS: High WNT7A expression was identified as a significant predictor of poor Overall Survival (OS) in the TCGA cohort (P < 0.05) and validated in the external cohort (P < 0.05). Multivariate analysis confirmed WNT7A as an independent prognostic risk factor (HR = 1.085, P = 0.036). Immunologically, WNT7A expression was positively correlated with MDSC infiltration (R = 0.43, P < 0.001), suggesting a shift towards an immune-tolerant phenotype. Mechanistically, GSEA revealed a robust activation of inflammatory signaling in the high-WNT7A group. Specifically, the TNFA Signaling via NF-κB pathway was significantly enriched(NES = 2.52, P < 0.001). Consistent with this pathway activation, WNT7A showed a statistically significant positive correlation with CCL2 (P < 0.001), a critical chemokine for MDSC recruitment, implicating the NF-κB/CCL2 axis in this process.

CONCLUSION: WNT7A serves as a prognostic biomarker linked to immune evasion in LUAD, potentially by modulating the NF-κB/CCL2/MDSC axis. This study identifies WNT7A as a potential therapeutic target to remodel the immune microenvironment, providing a rationale for future investigations into WNT-targeted strategies to improve immunotherapy efficacy.

PMID:41946008 | DOI:10.1016/j.cyto.2026.157144

A Hierarchical Error-Corrective Graph Framework for Autonomous Agents with LLM-Based Action Generation

cs.AI, q-bio.NC updates on arXiv.org

By: Cong Cao · Jingyao Zhang · Kun Tong

7 April 2026 at 12:00

arXiv:2603.08388v4 Announce Type: replace Abstract: We propose a Hierarchical Error-Corrective Graph FrameworkforAutonomousAgentswithLLM-BasedActionGeneration(HECG),whichincorporates three core innovations: (1) Multi-Dimensional Transferable Strategy (MDTS): by integrating task quality metrics (Q), confidence/cost metrics (C), reward metrics (R), and LLM-based semantic reasoning scores (LLM-Score), MDTS achieves multi-dimensional alignment between quantitative performance and semantic context, enabling more precise selection of high-quality candidate strate gies and effectively reducing the risk of negative transfer. (2) Error Matrix Classification (EMC): unlike simple confusion matrices or overall performance metrics, EMC provides structured attribution of task failures by categorizing errors into ten types, such as Strategy Errors (Strategy Whe) and Script Parsing Errors (Script-Parsing-Error), and decomposing them according to severity, typical actions, error descriptions, and recoverability. This allows precise analysis of the root causes of task failures, offering clear guidance for subsequent error correction and strategy optimization rather than relying solely on overall success rates or single performance metrics. (3) Causal-Context Graph Retrieval (CCGR): to enhance agent retrieval capabilities in dynamic task environments, we construct graphs from historical states, actions, and event sequences, where nodes store executed actions, next-step actions, execution states, transferable strategies, and other relevant information, and edges represent causal dependencies such as preconditions for transitions between nodes. CCGR identifies subgraphs most relevant to the current task context, effectively capturing structural relationships beyond vector similarity, allowing agents to fully leverage contextual information, accelerate strategy adaptation, and improve execution reliability in complex, multi-step tasks.

Reading view