Department of Gastroenterology, the Second Hospital of Dalian Medical University, Dalian, 116023, China.
Department of Pathology, the Second Hospital of Dalian Medical University, Dalian, 116023, China.
BMC Cancer. 2022 Aug 5;22(1):855. doi: 10.1186/s12885-022-09961-y.
Colorectal cancer (CRC) is the third most common cancer worldwide. However, limited effective biomarkers are associated with the tumorigenesis and prognosis of CRC.
The present study identified potential signatures from The Cancer Genome Atlas (TCGA) database and further validated the identified biomarkers in CRC tissues by immunohistochemistry (IHC).
The expression of insulin-like growth factor 1 receptor (IGF-1R) and Livin gene was significantly upregulated in CRC samples compared to the adjacent normal samples in the TCGA dataset. IHC indicated that IGF-1R and Livin protein levels are increased in CRC and adenoma tissues compared to normal tissues. Notably, the IGF-1R protein levels differed significantly between adenoma and CRC. The elevated IGF-1R and Livin expression was associated with CRC clinicopathological features, including age, gender, histological subtype, individual cancer stages, nodal metastasis, and TP53-mutant in TCGA. Additionally, the IGF-1R promoter methylation level was closely related to CRC. Consistent with the TCGA study, IHC indicated that overexpressed IGF-1R and Livin proteins were independent risk factors for stage and metastasis. A marked correlation was established between IGF-1R and Livin expression in CRC, while the survival map showed no significant correlation with CRC. Kaplan-Meier survival curves showed that CRC patients with high IGF-1R or Livin expression had a prolonged overall disease-free survival than those with low expression in TCGA.
IGF-1R and Livin are associated with CRC tumorigenesis and might be valuable for novel biomarker identification and targeted therapeutic strategy development.
结直肠癌(CRC)是全球第三大常见癌症。然而,与 CRC 的肿瘤发生和预后相关的有效生物标志物有限。
本研究从癌症基因组图谱(TCGA)数据库中鉴定出潜在的特征,并通过免疫组织化学(IHC)进一步验证了在 CRC 组织中鉴定出的生物标志物。
TCGA 数据集显示,与相邻正常样本相比,CRC 样本中胰岛素样生长因子 1 受体(IGF-1R)和 Livin 基因的表达显著上调。IHC 表明,与正常组织相比,CRC 和腺瘤组织中 IGF-1R 和 Livin 蛋白水平升高。值得注意的是,腺瘤和 CRC 之间的 IGF-1R 蛋白水平有显著差异。IGF-1R 和 Livin 表达的升高与 CRC 的临床病理特征相关,包括年龄、性别、组织学亚型、个体癌症分期、淋巴结转移和 TCGA 中的 TP53 突变。此外,IGF-1R 启动子甲基化水平与 CRC 密切相关。与 TCGA 研究一致,IHC 表明过度表达的 IGF-1R 和 Livin 蛋白是分期和转移的独立危险因素。在 CRC 中,IGF-1R 和 Livin 表达之间存在显著相关性,而生存图显示与 CRC 无显著相关性。Kaplan-Meier 生存曲线显示,在 TCGA 中,IGF-1R 或 Livin 高表达的 CRC 患者的总无病生存率长于低表达的患者。
IGF-1R 和 Livin 与 CRC 的肿瘤发生有关,可能对新型生物标志物的鉴定和靶向治疗策略的发展具有重要价值。