Zhong Fei, Mao Shining, Peng Shuangfu, Li Jiaqi, Xie YanTeng, Xia Ziqian, Chen Chao, Sun Aijun, Zhang Shasha, Wang Shiyan
Department of Laboratory Medicine, The Affiliated Huai'an Hospital of Xuzhou Medical University, The Second People's Hospital of Huai'an, Huai'an, Jiangsu, China.
Faculty of Life Science and Food Engineering, Huaiyin Institute of Technology, Huaian, Jiangsu, China.
Front Immunol. 2025 Mar 21;16:1521965. doi: 10.3389/fimmu.2025.1521965. eCollection 2025.
The SUSD3 protein, marked by the Sushi domain, plays a key role in cancer progression, with its expression linked to tumor advancement and patient prognosis. Altered SUSD3 levels could serve as a predictive biomarker for cancer progression. Recognized as a novel susceptibility marker, SUSD3 presents a promising target for antibody-based therapies, offering a potential approach for the prevention, diagnosis, and treatment of breast cancer.
Using the HPA and GeneMANIA platforms, the distribution of SUSD3 protein across tissues was analyzed, while expression levels in tumor and healthy tissues were compared using The Cancer Genome Atlas data. The TISCH and STOmics DB databases facilitated the mapping of SUSD3 expression in different cell types and its spatial relationship with cancer markers. Univariate Cox regression assessed the prognostic significance of SUSD3 expression in various cancers. Genomic alterations of SUSD3 were explored through the cBioPortal database. The potential of SUSD3 as a predictor of immunotherapy response was investigated using TIMER2.0, and GSEA/GSVA identified related biological pathways. Drugs targeting SUSD3 were identified through CellMiner, CTRP, and GDSC databases, complemented by molecular docking studies. experiments demonstrated that SUSD3 knockdown in breast cancer cell lines significantly reduced proliferation and migration.
SUSD3 expression variations in pan-cancer cohorts are closely linked to the prognosis of various malignancies. In the tumor microenvironment (TME), SUSD3 is predominantly expressed in monocytes/macrophages and CD4+ T cells. Research indicates a strong correlation between SUSD3 expression and key cancer immunotherapy biomarkers, immune cell infiltration, and immunomodulatory factors. To explore its immune regulatory role, StromalScore, ImmuneScore, ESTIMATE, and Immune Infiltration metrics were employed. Molecular docking studies revealed that selumetinib inhibits tumor cell proliferation. Finally, SUSD3 knockdown reduced cancer cell proliferation and migration.
These findings provide valuable insights and establish a foundation for further exploration of SUSD3's role in pan-carcinomas. Additionally, they offer novel perspectives and potential targets for the development of innovative therapeutic strategies in cancer treatment.
以寿司结构域为标志的SUSD3蛋白在癌症进展中起关键作用，其表达与肿瘤进展和患者预后相关。SUSD3水平的改变可作为癌症进展的预测生物标志物。作为一种新的易感标志物，SUSD3是基于抗体疗法的一个有前景的靶点，为乳腺癌的预防、诊断和治疗提供了一种潜在方法。
使用人类蛋白质图谱（HPA）和基因共表达网络分析工具（GeneMANIA）平台分析SUSD3蛋白在各组织中的分布，同时使用癌症基因组图谱（The Cancer Genome Atlas）数据比较肿瘤组织和健康组织中的表达水平。肿瘤免疫单细胞图谱（TISCH）和肿瘤单细胞数据库（STOmics DB）有助于绘制SUSD3在不同细胞类型中的表达及其与癌症标志物的空间关系。单因素Cox回归评估SUSD3表达在各种癌症中的预后意义。通过cBioPortal数据库探索SUSD3的基因组改变。使用TIMER2.0研究SUSD3作为免疫治疗反应预测指标的潜力，基因集富集分析（GSEA）/基因集变异分析（GSVA）确定相关生物学途径。通过细胞药物筛选数据库（CellMiner）、癌症治疗反应门户（CTRP）和基因表达综合数据库（GDSC）数据库确定靶向SUSD3的药物，并辅以分子对接研究。实验表明，乳腺癌细胞系中SUSD3基因敲低显著降低细胞增殖和迁移。
泛癌队列中SUSD3表达变异与各种恶性肿瘤的预后密切相关。在肿瘤微环境（TME）中，SUSD3主要在单核细胞/巨噬细胞和CD4+T细胞中表达。研究表明SUSD3表达与关键癌症免疫治疗生物标志物、免疫细胞浸润和免疫调节因子之间存在强相关性。为探索其免疫调节作用，采用了基质评分、免疫评分、ESTIMATE和免疫浸润指标。分子对接研究表明，司美替尼抑制肿瘤细胞增殖。最后，SUSD3基因敲低降低了癌细胞的增殖和迁移。
这些发现提供了有价值的见解，并为进一步探索SUSD3在泛癌中的作用奠定了基础。此外，它们为癌症治疗中创新治疗策略的开发提供了新的视角和潜在靶点。
