Chen Hualin, Ma Lin, Ji Zhigang, Dong Jie
Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China.
Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
Int J Med Sci. 2025 Aug 11;22(14):3737-3748. doi: 10.7150/ijms.110096. eCollection 2025.
: While the immunomodulatory function of FAM174B in bladder cancer (BLCA) has yet to be fully elucidated, elucidating its biological mechanisms could potentially enhance immunotherapeutic outcomes for this malignancy. : Bulk RNA-seq data from TCGA and GEO databases were analyzed to investigate FAM174B expression patterns and immune landscape characteristics in pan-cancer. The immunoregulatory role of FAM174B in BLCA was systematically evaluated through immune infiltration analysis, immunomodulator profiling, cancer-immunity cycle assessment, and immune checkpoint examination. Validation was performed using the IMvigor210 immunotherapy cohort and a combined GEO dataset (n=871). A machine learning-based immune-related signature was developed for prognostic and therapeutic response prediction. : FAM174B was highly expressed in cancer tissues across multiple human cancer types including BLCA. Specifically, FAM174B negatively correlated with various immunological features including immunoregulators and immune cell infiltration abundances, suggesting that FAM174B remodeled the microenvironment to a non-inflamed phenotype of BLCA. Besides, patients with high-FAM174B expression may process limited sensitivity to immunotherapy and increased likelihood of hyperprogression. Consensus molecular classification analysis indicated that elevated FAM174B is related to a luminal BLCA subtype which was characterized by reduced immune infiltration, inhibited immuno- and chemo-therapeutic responses, yet increased response to angiogenesis inhibitors and targeted therapy. Furthermore, the immune-related signature, formulated through a machine learning-integrated approach, is shown to be a dependable indicator for predicting cancer prognosis and the efficacy of immunotherapy responses for BLCA. : Given the pivotal role of FAM174B in shaping the non-inflamed tumor microenvironment of BLCA, therapeutic targeting of FAM174B may represent a promising strategy for BLCA management. Furthermore, FAM174B expression could serve as a potential biomarker for predicting molecular subtypes and treatment responsiveness in BLCA patients.
虽然FAM174B在膀胱癌（BLCA）中的免疫调节功能尚未完全阐明，但阐明其生物学机制可能会提高这种恶性肿瘤的免疫治疗效果。对来自TCGA和GEO数据库的批量RNA测序数据进行分析，以研究泛癌中FAM174B的表达模式和免疫景观特征。通过免疫浸润分析、免疫调节剂谱分析、癌症-免疫循环评估和免疫检查点检测，系统评估了FAM174B在BLCA中的免疫调节作用。使用IMvigor210免疫治疗队列和一个合并的GEO数据集（n=871）进行验证。开发了一种基于机器学习的免疫相关特征，用于预测预后和治疗反应。FAM174B在包括BLCA在内的多种人类癌症类型的癌组织中高表达。具体而言，FAM174B与包括免疫调节剂和免疫细胞浸润丰度在内的各种免疫特征呈负相关，这表明FAM174B将微环境重塑为BLCA的非炎症表型。此外，FAM174B高表达的患者可能对免疫治疗的敏感性有限，且超进展的可能性增加。共识分子分类分析表明，FAM174B升高与管腔BLCA亚型相关，其特征是免疫浸润减少、免疫和化疗反应受抑制，但对血管生成抑制剂和靶向治疗的反应增加。此外，通过机器学习整合方法制定的免疫相关特征被证明是预测BLCA癌症预后和免疫治疗反应疗效的可靠指标。鉴于FAM174B在塑造BLCA的非炎症肿瘤微环境中的关键作用，靶向FAM174B的治疗可能是BLCA管理的一种有前景的策略。此外，FAM174B表达可作为预测BLCA患者分子亚型和治疗反应性的潜在生物标志物。
