Wang Jingru, Gilani Sana Fatima, Noor Nazia, Ahmed Muhammad Rashid, Munazir Mehmooda, Zubair Ayesha, Sultan Rizwana, Abdel-Maksoud Mostafa A, Saleh Ibrahim A, Zomot Naser, Kodous Ahmad S, Ibrahim Shebl Salah, El-Tayeb Mohamed A, Aufy Mohammed, Zaky Mohamed Y, Hassan Syed Sairum, Hameed Yasir
Mengcheng County Hospital of Chinese Medicine China.
Bozhou Second Chinese Medicine Hospital China.
Am J Transl Res. 2024 Mar 15;16(3):738-754. doi: 10.62347/YORR3755. eCollection 2024.
While dysregulation of DSCC1 (DNA Replication And Sister Chromatid Cohesion 1) has been established in breast cancer and colorectal cancer, its associations with other tumors remain unclear. Therefore, this study was launched to explore the role of DSCC1 in pan-cancer.
In this study, we investigate the biological functions of DSCC1 across 33 solid tumors, elucidating its role in promoting oncogenesis and progression in various cancers through comprehensive analysis of multi-omics data.
We conducted a comprehensive analysis of DSCC1 expression using RNA-seq data from TCGA and GTEx databases across 30 cancer types. Striking variations were observed, with significant overexpression of DSCC1 identified in numerous cancers. Elevated DSCC1 level was strongly associated with poorer prognosis, shorter survival, and advanced tumor stages in kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), as indicated by Kaplan-Meier curves and GEPIA2 analysis. Further investigation into the molecular mechanisms revealed reduced DNA methylation in the DSCC1 promoter region in KIRP, LIHC, and LUAD, supporting enhanced RNA transcription. Protein expression analysis via the Human Protein Atlas (HPA) corroborated mRNA expression findings, showcasing elevated DSCC1 protein in KIRP, LIHC, and LUAD tissues. Mutational analysis using cBioPortal revealed alterations in 0.4% of KIRP, 17% of LIHC, and 5% of LUAD samples, predominantly characterized by amplification. Immune cell infiltration analysis demonstrated robust positive correlations between DSCC1 expression and CD8+ T cells, CD4+ T cells, and B cells, influencing the tumor microenvironment. STRING and gene enrichment analyses unveiled DSCC1's involvement in critical pathways, emphasizing its multifaceted impact. Notably, drug sensitivity analysis highlighted a significant correlation between DSCC1 mRNA expression and responses to 78 anticancer treatments, suggesting its potential as a predictive biomarker and therapeutic target for KIRP, LIHC, and LUAD. Finally, immunohistochemistry staining of clinical samples validated computational results, confirming elevated DSCC1 protein expression.
Overall, this study provides comprehensive insights into the pivotal role of DSCC1 in KIRP, LIHC, and LUAD initiation, progression, and therapeutic responsiveness, laying the foundation for further investigations and personalized treatment strategies.
虽然DSCC1（DNA复制与姐妹染色单体黏连蛋白1）失调在乳腺癌和结直肠癌中已有定论，但其与其他肿瘤的关联仍不明确。因此，本研究旨在探索DSCC1在泛癌中的作用。
在本研究中，我们调查了DSCC1在33种实体瘤中的生物学功能，通过对多组学数据的综合分析，阐明其在促进各种癌症的肿瘤发生和进展中的作用。
我们使用来自TCGA和GTEx数据库的RNA测序数据，对30种癌症类型中的DSCC1表达进行了全面分析。观察到显著差异，在许多癌症中发现DSCC1明显过表达。Kaplan-Meier曲线和GEPIA2分析表明，在肾肾乳头状细胞癌（KIRP）、肝细胞癌（LIHC）、肺腺癌（LUAD）中，DSCC1水平升高与较差的预后、较短的生存期和晚期肿瘤阶段密切相关。对分子机制的进一步研究发现，KIRP、LIHC和LUAD中DSCC1启动子区域的DNA甲基化减少，支持了RNA转录增强。通过人类蛋白质图谱（HPA）进行的蛋白质表达分析证实了mRNA表达结果，显示KIRP、LIHC和LUAD组织中DSCC1蛋白升高。使用cBioPortal进行的突变分析显示，0.4%的KIRP样本、17%的LIHC样本和5%的LUAD样本发生改变，主要特征为扩增。免疫细胞浸润分析表明，DSCC1表达与CD8 + T细胞、CD4 + T细胞和B细胞之间存在强烈的正相关，影响肿瘤微环境。STRING和基因富集分析揭示了DSCC1参与关键通路，强调了其多方面的影响。值得注意的是，药物敏感性分析突出了DSCC1 mRNA表达与78种抗癌治疗反应之间的显著相关性，表明其作为KIRP、LIHC和LUAD的预测生物标志物和治疗靶点的潜力。最后，临床样本的免疫组织化学染色验证了计算结果，证实DSCC1蛋白表达升高。
总体而言，本研究全面深入地揭示了DSCC1在KIRP、LIHC和LUAD的起始、进展和治疗反应性中的关键作用，为进一步研究和个性化治疗策略奠定了基础。
