Department of Gastroenterology, Ningbo First Hospital, Ningbo, China.
Department of Gastrointestinal Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, China.
BMC Cancer. 2020 Apr 15;20(1):305. doi: 10.1186/s12885-020-06743-2.
Colon adenocarcinoma (COAD) is one of the most lethal cancers. It is particularly important to accurately predict prognosis and to provide individualized treatment. Several lines of evidence suggest that genetic factors and clinicopathological characteristics are related to cancer onset and progression. The aim of this study was to identify potential prognostic genes and to develop a nomogram to predict survival and recurrence of COAD.
To identify potential prognostic genes in COAD, microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were obtained from GEO2R. Venn diagram was drawn to select those genes that were overexpressed in all datasets, and survival analyses were performed to determine the prognostic values of the selected genes. New nomograms were developed based on the genes that were significantly associated with prognosis. Clinicopathological data were obtained from The Cancer Genome Atlas (TCGA). Finally, the new nomograms were compared head-to-head comparison with the TNM nomogram.
From GSE21510, GSE110223, GSE113513 and GSE110224, a total of 834, 218, 236 and 613 overexpressed DEGs were screened out, respectively. The Venn diagram revealed that 12 genes appeared in all four profiles. After survival analyses, only INHBA expression was associated with both overall survival (OS) and disease-free survival (DFS). Multivariate analyses revealed that age, pathological N and pathological M were significant independent risk factors for OS. Age, pathological N, pathological M and INHBA were significant independent risk factors for DFS. Two prediction models predicted the probability of 3-year survival and 5-year survival for OS and DFS, respectively. The concordance indexes were 0.785 for 3-year overall survival, 0.759 for 5-year overall survival, 0.789 for 3-year disease-free survival and 0.757 for 5-year disease-free survival. The head-to-head comparison according to time-dependent ROC curves indicated that the new models had higher predictive accuracy. Decision curve analyses (DCA) indicated that the clinical value of the new models were higher than TNM models for predicting disease-free survival.
The combination of INHBA expression with a clinical nomogram improves prognostic power in colon adenocarcinoma, especially for predicting recurrence.
结肠腺癌（COAD）是最致命的癌症之一。准确预测预后并提供个体化治疗尤为重要。有几条证据表明，遗传因素和临床病理特征与癌症的发生和进展有关。本研究的目的是确定潜在的预后基因，并开发一个列线图来预测 COAD 的生存和复发。
为了鉴定 COAD 中的潜在预后基因，从基因表达综合数据库（GEO）中下载了微阵列数据集。使用 GEO2R 获得差异表达基因（DEGs）。绘制 Venn 图以选择在所有数据集中均过表达的基因，并进行生存分析以确定所选基因的预后价值。基于与预后显著相关的基因开发新的列线图。从癌症基因组图谱（TCGA）中获取临床病理数据。最后，将新的列线图与 TNM 列线图进行头对头比较。
从 GSE21510、GSE110223、GSE113513 和 GSE110224 中，分别筛选出 834、218、236 和 613 个过表达的 DEGs。Venn 图显示，在四个图谱中均有 12 个基因出现。经过生存分析，只有 INHBA 的表达与总生存（OS）和无病生存（DFS）均相关。多因素分析显示，年龄、病理 N 和病理 M 是 OS 的显著独立危险因素。年龄、病理 N、病理 M 和 INHBA 是 DFS 的显著独立危险因素。两个预测模型分别预测了 OS 和 DFS 的 3 年生存率和 5 年生存率的概率。一致性指数分别为 0.785 用于 3 年总生存率，0.759 用于 5 年总生存率，0.789 用于 3 年无病生存率，0.757 用于 5 年无病生存率。根据时间依赖性 ROC 曲线的头对头比较表明，新模型的预测准确性更高。决策曲线分析（DCA）表明，新模型在预测无病生存方面的临床价值高于 TNM 模型。
INHBA 表达与临床列线图相结合可提高结肠腺癌的预后能力，特别是对预测复发的能力。
