Background: Cancer represents a widespread global health challenge impacting millions of individuals worldwide. Identifying new targets for cancer treatment is a crucial step in developing more effective therapies. Among these potential targets, Coactosin-like protein 1 (COTL1), a cytoskeleton-associated protein with critical roles in cell migration, adhesion, and signaling, has shown involvement in tumor progression.
Methods: GSCA, TIMER, SangerBox database were used to explore the COTL1 expression across different tumor types. We employed the TCGA Pan-Atlas Cancer Genomics Dataset, which is available through the cBioportal platform, to explore genetic alterations in COTL1. We conduct a comprehensive analysis of COTL1, encompassing gene expression, clinical prognosis, RNA modification, immunotherapy, and cancer stemness through SangerBox database. Clinical samples were validated using immunohistochemistry.
Results: Our analysis revealed that COTL1 is highly expressed in most cancers and correlates with decreased survival in Glioma, Glioblastoma multiforme, and pan-kidney cohorts. Furthermore, COTL1 was found to be associated with DNA and RNA stemness in 20 and 22 different tumor types, respectively. Additionally, COTL1 showed positive correlations with immunological checkpoints and immune infiltration cells. It was also linked to tumor mutation burden (TMB), microsatellite instability (MSI), neoantigen (NEO), and programmed death ligand 1 (PD-L1), all of which are potential targets for immunotherapies. Moreover, a favorable relationship was demonstrated between genomic-instability markers such as heterozygosity (LOH), homologous recombination deficiency (HRD), and mutant allele tumor heterogeneity (MATH) with COTL1. Furthermore, our findings confirmed a positive correlation between COTL1 expression, CD8, and PD-L1 in LGG, as well as an association of high COTL1 expression with decreased patient survival in LGG.
Conclusion: Based on these compelling findings, COTL1 may hold significant clinical implications for the development of novel cancer therapies and serve as a potential target for tumors associated with immunotherapy in the future.



中文翻译：

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辅乳糖蛋白样蛋白 1 (COTL1) 可能成为一种免疫学和预后生物标志物：从泛癌症分析到低级别胶质瘤验证

背景：癌症是一个广泛的全球健康挑战，影响着全世界数百万人。确定癌症治疗的新靶点是开发更有效疗法的关键一步。在这些潜在靶标中，辅乳糖蛋白样蛋白 1 (COTL1) 是一种细胞骨架相关蛋白，在细胞迁移、粘附和信号传导中发挥关键作用，已显示与肿瘤进展有关。
方法：利用GSCA、TIMER、SangerBox数据库探讨COTL1在不同肿瘤类型中的表达情况。我们利用 TCGA 泛阿特拉斯癌症基因组数据集（可通过 cBioportal 平台获取）来探索 COTL1 的遗传改变。我们通过SangerBox数据库对COTL1进行全面分析，包括基因表达、临床预后、RNA修饰、免疫治疗和癌症干性。使用免疫组织化学对临床样本进行验证。
结果：我们的分析显示，COTL1 在大多数癌症中高表达，并与神经胶质瘤、多形性胶质母细胞瘤和泛肾队列的生存率降低相关。此外，发现 COTL1 分别与 20 种和 22 种不同肿瘤类型的 DNA 和 RNA 干细胞相关。此外，COTL1 与免疫检查点和免疫浸润细胞呈正相关。它还与肿瘤突变负荷 (TMB)、微卫星不稳定性 (MSI)、新抗原 (NEO) 和程序性死亡配体 1 (PD-L1) 相关，所有这些都是免疫疗法的潜在靶标。此外，杂合性 (LOH)、同源重组缺陷 (HRD) 和突变等位基因肿瘤异质性 (MATH) 等基因组不稳定标记与 COTL1 之间存在良好的关系。此外，我们的研究结果证实了 LGG 中 COTL1 表达、CD8 和 PD-L1 之间存在正相关性，以及 COTL1 高表达与 LGG 中患者生存率降低之间的关联。
结论：基于这些令人信服的发现，COTL1 可能对新型癌症疗法的开发具有重要的临床意义，并作为未来与免疫疗法相关的肿瘤的潜在靶点。