Department of Oncology, The Third People's Hospital of Chengdu, Chengdu, 610014, China.
Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610042, China.
Sci Rep. 2024 Feb 26;14(1):4686. doi: 10.1038/s41598-024-54937-6.
With the emergence of targeted inhibition strategies for Hedgehog signaling in cancer, multiple Hedgehog signaling pathway-related biomarkers have become the focus of research. SsGSEA algorithm was employed to analyze the Hedgehog pathway scores of samples in TCGA-HNSC dataset and divide them into two groups. Weighted co-expression network analysis was performed to identify modules strongly associated with the Hedgehog pathway. Differentially up-regulated genes in tumor samples in comparison to the normal ones were screened by Limma, in which genes belonging to modules strongly related to Hedgehog pathway were further filtered by LASSO reduction and multivariate Cox regression analysis to develop a model. ESTIMATE and CIBERSORT were served to characterize the tumor microenvironment (TME). TIDE assessed immunotherapy response. Hedgehog pathway activity was significantly higher in head and neck squamous cell carcinoma (HNSCC) tissues than in normal tissues and was correlated with HNSCC survival, glycan, cofactors and vitamins, drug metabolism, and matrix scores. Six genes (SLC2A3, EFNB2, OAF, COX4I2, MT2A and TXNRD1) were captured to form a Hedgehog associated 6-gene signature, and the resulting risk score was an independent indicator of HNSCC prognosis. It was significantly positively correlated with stromal score, metabolism, angiogenesis and inflammatory response. Patients in low-risk group with a low TIDE score had higher immunotherapy sensitivity relative to those in high-risk group. This study revealed novel findings of the Hedgehog pathway in HNSCC progression and opened up a Hedgehog pathology-related signature to help identify risk factors contributing to HNSCC progression and help predict immunotherapy outcomes.
随着针对癌症 Hedgehog 信号传导的靶向抑制策略的出现，多种 Hedgehog 信号传导途径相关生物标志物已成为研究焦点。使用 SsGSEA 算法分析 TCGA-HNSC 数据集样本中的 Hedgehog 途径评分，并将其分为两组。进行加权共表达网络分析以识别与 Hedgehog 途径强烈相关的模块。通过 Limma 筛选肿瘤样本中与正常样本相比上调的基因，通过 LASSO 减少和多变量 Cox 回归分析进一步筛选与 Hedgehog 途径强烈相关的模块中的基因，以开发模型。ESTIMATE 和 CIBERSORT 用于表征肿瘤微环境 (TME)。TIDE 评估免疫治疗反应。Hedgehog 途径活性在头颈部鳞状细胞癌 (HNSCC) 组织中明显高于正常组织，与 HNSCC 生存、聚糖、辅助因子和维生素、药物代谢和基质评分相关。捕获六个基因 (SLC2A3、EFNB2、OAF、COX4I2、MT2A 和 TXNRD1) 形成 Hedgehog 相关的 6 个基因特征，所得风险评分是 HNSCC 预后的独立指标。它与基质评分、代谢、血管生成和炎症反应呈显著正相关。低风险组中 TIDE 评分低的患者相对于高风险组的患者具有更高的免疫治疗敏感性。本研究揭示了 Hedgehog 途径在 HNSCC 进展中的新发现，并开辟了 Hedgehog 病理学相关的特征，以帮助确定导致 HNSCC 进展的风险因素，并帮助预测免疫治疗结果。
