Department of Urology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, China.
The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
J Cell Mol Med. 2024 Nov;28(22):e70196. doi: 10.1111/jcmm.70196.
Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) belongs to the SPARC family of matricellular proteins. However, underlying functions of SPARCL1 in bladder cancer (BCa) remain understudied. We performed an integrated search for the expression patterns of SPARCL1 in relation to various clinicopathological features of BCa. We then carried out Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and gene set enrichment analysis (GSEA). Furthermore, we investigated the correlations between SPARCL1 and immunological features, such as tumour mutation burden (TMB), immune activation processes, immune checkpoint expression, tumour immune dysfunction and exclusion (TIDE) scores, and chemotherapeutic sensitivity in BCa. Our analysis revealed that SPARCL1 was downregulated across multiple cancers. In BCa, elevated SPARCL1 was linked with advanced histopathologic stage, higher T and N stage, and poorer prognosis in the clinical cohort. In vitro experiments demonstrated that increased SPARCL1 expression inhibited cell proliferation, migration, and invasion. Additionally, highly expressed SPARCL1 was linked to elevated immune, stromal and ESTIMATE scores, as well as an increase in naive B cells, M2 macrophages, and resting mast cells. We observed a moderate correlation between SPARCL1 expression and CD163, VSIG4 and MS4A4A, which are markers of M2 macrophages. Furthermore, SPARCL1 expression was positively related to TMB, immune activation processes, TIDE scores, immune checkpoint expression, and chemotherapeutic sensitivity in BCa. Our study highlights the potential involvement of SPARCL1 in macrophage recruitment and polarization and suggests its utility as a biomarker for prognosis in BCa.
分泌型酸性富含半胱氨酸蛋白 1（SPARCL1）属于基质细胞衍生蛋白 SPARC 家族。然而，SPARCL1 在膀胱癌（BCa）中的潜在功能仍有待研究。我们对 SPARCL1 的表达模式与 BCa 的各种临床病理特征之间的关系进行了综合搜索。然后，我们进行了基因本体论（GO）富集分析、京都基因与基因组百科全书（KEGG）通路富集分析和基因集富集分析（GSEA）。此外，我们还研究了 SPARCL1 与免疫特征之间的相关性，例如肿瘤突变负担（TMB）、免疫激活过程、免疫检查点表达、肿瘤免疫功能障碍和排除（TIDE）评分以及 BCa 的化疗敏感性。我们的分析表明 SPARCL1 在多种癌症中下调。在 BCa 中，SPARCL1 升高与较高的组织病理学分期、更高的 T 和 N 分期以及临床队列中的预后较差有关。体外实验表明，增加 SPARCL1 表达可抑制细胞增殖、迁移和侵袭。此外，高表达的 SPARCL1 与较高的免疫、基质和 ESTIMATE 评分以及幼稚 B 细胞、M2 巨噬细胞和静止肥大细胞的增加有关。我们观察到 SPARCL1 表达与 M2 巨噬细胞标志物 CD163、VSIG4 和 MS4A4A 之间存在中等相关性。此外，SPARCL1 表达与 BCa 中的 TMB、免疫激活过程、TIDE 评分、免疫检查点表达和化疗敏感性呈正相关。我们的研究强调了 SPARCL1 参与招募和极化巨噬细胞的潜力，并表明其可作为 BCa 预后的生物标志物。
