Shi Chunlei, Xie Yongjie, Li Xueyang, Li Guangming, Liu Weishuai, Pei Wenju, Liu Jing, Yu Xiaozhou, Liu Tong
Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Tianjin General Surgery Institute, Tianjin, China.
Front Cell Dev Biol. 2022 Jan 26;9:815104. doi: 10.3389/fcell.2021.815104. eCollection 2021.
Colon adenocarcinoma (COAD) is one of the most prevalent cancers worldwide and has become a leading cause of cancer death. Although many potential biomarkers of COAD have been screened with the bioinformatics method, it is necessary to explore novel markers for the diagnosis and appropriate individual treatments for COAD patients due to the high heterogeneity of this disease. Epithelial-to-mesenchymal transition (EMT)-mediated tumor metastasis suggests poor prognosis of cancers. Ferroptosis is involved in tumor development. EMT signaling can increase the cellular sensitivity to ferroptosis in tumors. The aim of our study is finding novel prognostic biomarkers to determine COAD patients for predicting efficiency of metastasis status and targeting precise ferroptosis-related therapy. A novel gene signature related to metastasis and ferroptosis was identified combing with risk model and WGCNA analysis with R software. The biological functions and predictive ability of the signature in COAD were explored through bioinformatics analysis. We established a four-gene prognostic signature (MMP7, YAP1, PCOLCE, and HOXC11) based on EMT and ferroptosis related genes and validated the reliability and effectiveness of this model in COAD. This four-gene prognostic signature was closely connected with metastasis and ferroptosis sensitivity of COAD. Moreover, WGCNA analysis further confirmed the correlation between PCOLCE, HOXC11, and liver and lymphatic invasion of COAD. The four genes may become potential prognostic biomarkers to identify COAD patients with metastasis. Moreover, this four-gene signature may be able to determine the COAD suitable with ferroptosis induction therapy. Finally, PCOLCE2 and HOXC11 were selected individually because of their novelties and precise prediction ability. Overall, this signature provided novel possibilities for better prognostic evaluation of COAD patients and may be of great guiding significance for individualized treatment and clinical decision.
结肠腺癌（COAD）是全球最常见的癌症之一，已成为癌症死亡的主要原因。尽管已通过生物信息学方法筛选出许多COAD的潜在生物标志物，但由于该疾病的高度异质性，仍有必要探索新的标志物用于COAD患者的诊断和个体化治疗。上皮-间质转化（EMT）介导的肿瘤转移提示癌症预后不良。铁死亡参与肿瘤发展。EMT信号可增加肿瘤细胞对铁死亡的敏感性。本研究的目的是寻找新的预后生物标志物，以确定COAD患者的转移状态预测效率，并靶向精确的铁死亡相关治疗。结合风险模型和R软件的WGCNA分析，鉴定了一个与转移和铁死亡相关的新基因特征。通过生物信息学分析探索了该特征在COAD中的生物学功能和预测能力。我们基于EMT和铁死亡相关基因建立了一个四基因预后特征（MMP7、YAP1、PCOLCE和HOXC11），并验证了该模型在COAD中的可靠性和有效性。这个四基因预后特征与COAD的转移和铁死亡敏感性密切相关。此外，WGCNA分析进一步证实了PCOLCE、HOXC11与COAD肝转移和淋巴转移之间的相关性。这四个基因可能成为识别有转移的COAD患者的潜在预后生物标志物。此外，这个四基因特征可能能够确定适合铁死亡诱导治疗的COAD患者。最后，由于PCOLCE2和HOXC11的新颖性和精确预测能力，分别对它们进行了选择。总体而言，该特征为更好地评估COAD患者的预后提供了新的可能性，可能对个体化治疗和临床决策具有重要指导意义。
