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一种新型三长链非编码 RNA 标志物预测头颈部鳞状细胞癌患者的总生存期。

A Novel Three-lncRNA Signature Predicts the Overall Survival of HNSCC Patients.

机构信息

Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.

出版信息

Ann Surg Oncol. 2021 Jun;28(6):3396-3406. doi: 10.1245/s10434-020-09210-1. Epub 2020 Oct 23.

Abstract

BACKGROUND

A number of long non-coding RNAs (lncRNAs) have been found to be involved in tumor progression and associated with disease prognoses in various types of cancer. Our study identified a novel three-lncRNA signature to predict survival of head and neck squamous cell caner (HNSCC) patients.

METHODS

We utilized The Cancer Genome Atlas (TCGA) cohort to screen out overall survival (OS)-associated lncRNAs in HNSCC and further developed a model to identify a lncRNA signature for evaluating disease status and prognosis. The lncRNA signature was then validated in HNSCC patients from our Fudan University Shanghai Cancer Center (FUSCC) cohort.

RESULTS

LINC02434, AL139327.2, and AC126175.1 were identified by multivariable Cox regression analyses of independent risk factors for deceased status. We built a risk score model based on the three-lncRNA signature using coefficient of multivariable Cox regression and expression value of the three lncRNAs. The high-risk signature score was significantly associated with decreased OS in both the TCGA cohort and the FUSCC cohort. The high-risk group had worse overall survival than the low-risk group in TCGA cohort. To further validate the robustness of three-lncRNA signature risk score model developed in the TCGA dataset, the performance of risk score also evaluated in our institute FUSCC cohort. Additionally, the signature score showed a positive correlation with aggressive outcomes of HNSCC, such as III/IV stage, TP53 mutation, and PI3KCA mutation. The gene set enrichment analysis indicates that the risk score is associated with cancer metastasis-related pathways. Several cancer-related pathways, such as epithelial mesenchymal transition, TNFα signaling via NF-κB, MYC targets, and angiogenesis.

CONCLUSIONS

The three-lncRNA signature could provide a novel prediction insight into the prognosis of HNSCC patients. The three-lncRNA signature was identified as a predictor of poor prognoses in HNSCC, which may serve as a potential therapeutic target.

摘要

背景

许多长链非编码 RNA(lncRNAs)已被发现参与肿瘤进展,并与各种类型癌症的疾病预后相关。我们的研究确定了一个新的三 lncRNA 特征,以预测头颈部鳞状细胞癌(HNSCC)患者的生存。

方法

我们利用癌症基因组图谱(TCGA)队列筛选出与 HNSCC 总生存(OS)相关的 lncRNAs,并进一步开发了一种模型来识别评估疾病状态和预后的 lncRNA 特征。然后在我们复旦大学上海癌症中心(FUSCC)的 HNSCC 患者队列中验证了 lncRNA 特征。

结果

多变量 Cox 回归分析独立死亡状态的危险因素,确定了 LINC02434、AL139327.2 和 AC126175.1。我们使用多变量 Cox 回归的系数和三个 lncRNA 的表达值,基于三个 lncRNA 特征构建了风险评分模型。高风险特征评分与 TCGA 队列和 FUSCC 队列的 OS 降低显著相关。高风险组的总生存明显低于 TCGA 队列的低风险组。为了进一步验证 TCGA 数据集开发的三 lncRNA 特征风险评分模型的稳健性,还在我们的研究所 FUSCC 队列中评估了风险评分的性能。此外,该特征评分与 HNSCC 的侵袭性结局呈正相关,如 III/IV 期、TP53 突变和 PI3KCA 突变。基因集富集分析表明,风险评分与癌症转移相关途径相关。几个癌症相关途径,如上皮间质转化、通过 NF-κB 的 TNFα 信号转导、MYC 靶点和血管生成。

结论

三 lncRNA 特征可为 HNSCC 患者的预后提供新的预测见解。三 lncRNA 特征被确定为 HNSCC 不良预后的预测因子,可能成为潜在的治疗靶点。

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