Department of Urology, Hunan Aerospace Hospital, Changsha, China.
Xiangya School of Medicine, Central South University, Changsha, China.
Sci Rep. 2024 Nov 3;14(1):26545. doi: 10.1038/s41598-024-77971-w.
Bladder cancer (BLCA), ranking as the tenth most prevalent malignancy globally, imposes a substantial public health and socio-economic challenge. Despite ongoing efforts by urologists to identify novel molecular subtypes and treatment paradigms, the intrinsic heterogeneity of BLCA continues to obstruct the efficacy of current diagnostic and therapeutic evaluations, leaving a gap in the comprehensive management of BLCA. This necessitates an in-depth investigation into the BLCA tumor microenvironment (TME) to identify pivotal molecules like MFAP3L. Our research concentrated on MFAP3L, commencing with a pan-cancer analysis of its immune profile. We discovered that MFAP3L exhibits a significant negative correlation with numerous immune components and markers in BLCA, a trend not observed in other cancer types. Within the TCGA-BLCA cohort, patients were classified into High-MFAP3L and Low-MFAP3L groups according to their MFAP3L transcript levels. Our exploration into the BLCA TME delved into immune infiltration, molecular subtype patterns, and treatment preferences within these MFAP3L groups. High MFAP3L expression was linked to favorable prognoses, luminal subtypes, and low immune infiltration, inversely associated with various immune molecules and characteristics. Additionally, high MFAP3L expressors exhibited diminished immune checkpoint levels, suggesting enhanced immunotherapy tolerance and sensitivity to oncogenic pathway targeting. Conversely, low MFAP3L expression correlated with poor outcomes, basal subtypes, increased immune infiltration, and heightened gene mutation rates, alongside sensitivity to radiotherapy, EGFR-targeted treatments, and immunotherapy. Hence, MFAP3L emerges as a critical yet underexplored gene in BLCA, offering insights into immune status within the TME and aiding in molecular subtyping and therapeutic decision-making.
膀胱癌（BLCA），作为全球第十大常见恶性肿瘤，对公共卫生和社会经济构成了重大挑战。尽管泌尿科医生一直在努力寻找新的分子亚型和治疗模式，但 BLCA 的固有异质性仍然阻碍了当前诊断和治疗评估的效果，导致 BLCA 的综合管理存在空白。这需要深入研究 BLCA 的肿瘤微环境（TME），以确定像 MFAP3L 这样的关键分子。我们的研究集中在 MFAP3L 上，从其免疫特征的泛癌症分析开始。我们发现 MFAP3L 在 BLCA 中与许多免疫成分和标志物呈显著负相关，而在其他癌症类型中则没有观察到这种趋势。在 TCGA-BLCA 队列中，根据 MFAP3L 转录水平将患者分为高 MFAP3L 和低 MFAP3L 组。我们对 BLCA TME 的探索深入研究了这些 MFAP3L 组中的免疫浸润、分子亚型模式和治疗偏好。高 MFAP3L 表达与良好的预后、腔型亚型和低免疫浸润有关，与各种免疫分子和特征呈负相关。此外，高 MFAP3L 表达者表现出免疫检查点水平降低，表明增强了免疫治疗耐受性和对致癌途径靶向治疗的敏感性。相反，低 MFAP3L 表达与不良结局、基底型亚型、增加的免疫浸润和更高的基因突变率相关，同时对放疗、EGFR 靶向治疗和免疫治疗敏感。因此，MFAP3L 是 BLCA 中一个关键但未被充分探索的基因，为 TME 中的免疫状态提供了深入了解，并有助于分子亚型分类和治疗决策。
