The National Engineering Research Center for Bioengineering Drugs and the Technologies, The Institute of Translational Medicine, Nanchang University, Nanchang, China.
Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Medicine (Baltimore). 2023 Sep 29;102(39):e35348. doi: 10.1097/MD.0000000000035348.
The combination of mRNA and lncRNA profiles for establishing an integrated mRNA-lncRNA prognostic signature has remained unexplored in cholangiocarcinoma (CCA) patients. We utilized a training dataset of 36 samples from The Cancer Genome Atlas dataset and a validation cohort (GSE107943) of 30 samples from Gene Expression Omnibus. Two mRNAs (CFHR3 and PIWIL4) and 2 lncRNAs (AC007285.1 and AC134682.1) were identified to construct the integrated signature through a univariate Cox regression (P-value = 1.35E-02) and a multivariable Cox analysis (P-value = 3.07E-02). Kaplan-Meier curve showed that patients with low risk scores had notably prolonged overall survival than those with high risk scores (P-value = 4.61E-03). Subsequently, the signature was validated in GSE107943 cohort with an area under the curve of 0.750 at 1-year and 0.729 at 3-year. The signature was not only independent from diverse clinical features (P-value = 3.07E-02), but also surpassed other clinical characteristics as prognostic biomarkers with area under the curve of 0.781 at 3-year. Moreover, the weighted gene co-expression network analysis and gene enrichment analyses found that the integrated signature were associated with metabolic-related biological process and lipid metabolism pathway, which has been implicated in the pathogenesis of CCA. Taken together, we developed an integrated mRNA-lncRNA signature that had an independent prognostic value in the risk stratification of patients with CCA.
mRNA 和 lncRNA 谱的联合用于建立综合的 mRNA-lncRNA 预后标志物在胆管癌（CCA）患者中尚未得到探索。我们利用了来自癌症基因组图谱数据集的 36 个样本的训练数据集和来自基因表达综合数据库的 30 个样本的验证队列（GSE107943）。通过单变量 Cox 回归（P 值=1.35E-02）和多变量 Cox 分析（P 值=3.07E-02），鉴定出 2 个 mRNAs（CFHR3 和 PIWIL4）和 2 个 lncRNAs（AC007285.1 和 AC134682.1）来构建综合标志物。Kaplan-Meier 曲线表明，低风险评分的患者总生存期明显长于高风险评分的患者（P 值=4.61E-03）。随后，该标志物在 GSE107943 队列中进行了验证，在 1 年时的曲线下面积为 0.750，在 3 年时为 0.729。该标志物不仅独立于各种临床特征（P 值=3.07E-02），而且作为预后生物标志物的曲线下面积为 0.781，超过了其他临床特征。此外，加权基因共表达网络分析和基因富集分析发现，综合标志物与代谢相关的生物学过程和脂质代谢途径有关，这与 CCA 的发病机制有关。总之，我们开发了一种综合的 mRNA-lncRNA 标志物，在 CCA 患者的风险分层中具有独立的预后价值。
