Pan Binyang, Shi Haochun, Shan Guangyao, Wu Gujie, Rao Kungeng, Liang Jiaqi, Jin Xing, Bi Guoshu, Zhao Mengnan, Guo Weigang
Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Department of Thoracic Surgery and Urology, Shigatse People's Hospital, Shigatse, Tibet Autonomous Region, China.
Heliyon. 2024 Sep 21;10(19):e38078. doi: 10.1016/j.heliyon.2024.e38078. eCollection 2024 Oct 15.
ESCC presents a significant global health challenge due to its high mortality rates and varying responses to treatment. This underscores the critical need for novel diagnostic and predictive biomarkers to improve treatment outcomes. Initially, we conducted single-cell transcriptome sequencing on a total of 128,688 cells obtained from 10 patients as part of our research. Utilizing machine learning and cross-validation techniques, we developed a model incorporating 12 genes that distinguish malignant cells from non-malignant ones. In vitro, we explored the effects of IGFBP2 knockdown on the proliferation, invasion, and migration of ESCC cells. The clinical relevance of IGFBP2 was confirmed through IHC and Kaplan-Meier survival analyses. Furthermore, using bioinformatics tools such as GSVA and xCell on public databases, we discovered that high expression of IGFBP2 is associated with an immunosuppressive tumor microenvironment in ESCC, characterized by reduced CD8 T cell infiltration. This was validated then through IHC. In summary, our study integrates single-cell sequencing and sophisticated computational techniques to highlight IGFBP2 as a promising biomarker and therapeutic target in ESCC.
由于其高死亡率和对治疗的不同反应,食管癌给全球健康带来了重大挑战。这突出表明迫切需要新的诊断和预测生物标志物来改善治疗效果。最初,作为我们研究的一部分,我们对从10名患者身上获取的总共128,688个细胞进行了单细胞转录组测序。利用机器学习和交叉验证技术,我们开发了一个包含12个基因的模型,该模型可区分恶性细胞和非恶性细胞。在体外,我们研究了IGFBP2基因敲低对食管癌细胞增殖、侵袭和迁移的影响。通过免疫组化和Kaplan-Meier生存分析证实了IGFBP2的临床相关性。此外,我们使用公共数据库上的GSVA和xCell等生物信息学工具发现,IGFBP2的高表达与食管癌中免疫抑制性肿瘤微环境相关,其特征是CD8 T细胞浸润减少。然后通过免疫组化对这一结果进行了验证。总之,我们的研究整合了单细胞测序和复杂的计算技术,以突出IGFBP2作为食管癌中有前景的生物标志物和治疗靶点。