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对结直肠鳞状细胞癌的系统全面分析:对诊断和治疗的启示。

A systematic and comprehensive analysis of colorectal squamous cell carcinoma: Implication for diagnosis and treatment.

机构信息

Department of Gastrointestinal Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, China.

Department of Radiation Oncology, North China University of Science and Technology Affiliated People's Hospital, Tangshan, Hebei, China.

出版信息

Cancer Med. 2022 Jun;11(12):2492-2502. doi: 10.1002/cam4.4616. Epub 2022 Feb 23.

Abstract

BACKGROUND

This study was aimed at establishing a nomogram for survival prediction of Colorectal squamous cell carcinoma (CSCC), understanding the molecular pathogenesis, exploring a better treatment, and predicting the potential therapeutic agents.

METHODS

Surveillance, Epidemiology, and End Results (SEER) database was used to obtained CSCC patients and the nomogram was performed. Propensity score matching (PSM), Kaplan-Meier analysis, subgroup analysis, and interaction test were used to explore the better treatment strategy for CSCC. Bioinformatics were used to explore the molecular mechanism and potential therapeutic drugs of CSCC.

RESULTS

A total of 3949 CSCC patients were studied. The nomogram was constructed and evaluated to have a good performance. We found that the radiotherapy had a better effect than surgery, and the difference between radiotherapy and combined therapy was not significant. 821 differentially expressed genes in CSCC were obtained from GSE6988 dataset. DNA damage repair, mismatch repair, and cell cycle pathways might contribute to CSCC occurrence as indicated by KEGGpathway and GSEA analysis. Transcription factors analysis revealed that TP63 and STAT1 may have an important role in occurrence and development of CSCC. 1607 potential drugs against CSCC were found using the CMAP database, and molecular docking was carried out to show the binding energy between TP63 and drugs.

CONCLUSIONS

A good prognosis nomogram was constructed for CSCC. We also have a better understanding of the underlying molecular mechanisms of occurrence and development of CSCC and predicted potential therapeutic drugs, providing a theoretical basis for the treatment of CSCC.

摘要

背景

本研究旨在建立结直肠鳞状细胞癌(CSCC)的生存预测列线图,了解其分子发病机制,探索更好的治疗方法,并预测潜在的治疗药物。

方法

利用监测、流行病学和最终结果(SEER)数据库获取 CSCC 患者,并进行列线图分析。采用倾向评分匹配(PSM)、Kaplan-Meier 分析、亚组分析和交互检验来探讨 CSCC 的最佳治疗策略。利用生物信息学方法探讨 CSCC 的分子机制和潜在的治疗药物。

结果

共纳入 3949 例 CSCC 患者。构建并评估了列线图,结果显示其具有良好的性能。我们发现放疗的效果优于手术,且放疗与联合治疗之间的差异无统计学意义。从 GSE6988 数据集获得了 821 个 CSCC 差异表达基因。KEGGpathway 和 GSEA 分析表明,DNA 损伤修复、错配修复和细胞周期途径可能与 CSCC 的发生有关。转录因子分析表明,TP63 和 STAT1 可能在 CSCC 的发生和发展中起重要作用。利用 CMAP 数据库发现了 1607 种针对 CSCC 的潜在药物,并进行了分子对接,以显示 TP63 与药物的结合能。

结论

构建了 CSCC 的良好预后列线图。我们还进一步了解了 CSCC 发生和发展的潜在分子机制,并预测了潜在的治疗药物,为 CSCC 的治疗提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/527a/9189455/bebd07c29452/CAM4-11-2492-g001.jpg

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