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五项关键的与预后相关的自噬基因对 40-60 岁女性乳腺癌患者进行分层。

Five crucial prognostic-related autophagy genes stratified female breast cancer patients aged 40-60 years.

机构信息

Surgical Department of Breast Thyroid Surgery, Xuchang Central Hospital, No. 30 Huatuo Road, Weidu District, Xu Chang, 461600, Henan Province, China.

出版信息

BMC Bioinformatics. 2021 Dec 7;22(1):580. doi: 10.1186/s12859-021-04503-y.

Abstract

BACKGROUND

Autophagy is closely related to the progression of breast cancer. The aim at this study is to establish a prognostic-related model comprised of hub autophagy genes (AGs) to assess patient prognosis. Simultaneously, the model can guide clinicians to make up individualized strategies and stratify patients aged 40-60 years based on risk level.

METHODS

The hub AGs were identified with univariate COX regression and LASSO regression. The functions and alterations of these selected AGs were analyzed as well. Moreover, the multivariate COX regression and correlation analysis between hub AGs and clinicopathological parameters were done.

RESULTS

Totally, 33 prognostic-related AGs were obtained from the univariate COX regression (P < 0.05). SERPINA1, HSPA8, HSPB8, MAP1LC3A, and DIRAS3 were identified to constitute the prognostic model by the LASSO regression. The survival curve of patients in the high-risk and low-risk groups was statistically significant (P < 0.05). The 3-year and 5-year ROC displayed that their AUC value reached 0.762 and 0.825, respectively. Stage and risk scores were independent risk factors relevant to prognosis. RB1CC1, RPS6KB1, and BIRC6 were identified as the most predominant mutant genes. It was found that AGs were mainly involved in regulating the endopeptidases synthesis and played important roles in the ErbB signal pathway. SERPIN1, risk score was closely related to the stage (P < 0.05); HSPA8, risk score were closely related to T stag (P < 0.05); HSPB8 was closely related to N stag (P < 0.05).

CONCLUSIONS

Our prognostic model had the relatively robust predictive ability on prognosis for patients aged 40-60 years. If the stage was added into the prognostic model, the predictive ability would be more powerful.

摘要

背景

自噬与乳腺癌的进展密切相关。本研究旨在建立一个由关键自噬基因(AGs)组成的预后相关模型,以评估患者的预后。同时,该模型可以指导临床医生制定个体化策略,并根据风险水平对 40-60 岁的患者进行分层。

方法

使用单因素 COX 回归和 LASSO 回归鉴定关键 AGs。分析这些选定 AGs 的功能和改变。此外,还进行了多因素 COX 回归和关键 AGs 与临床病理参数之间的相关性分析。

结果

从单因素 COX 回归中获得了 33 个与预后相关的 AGs(P<0.05)。通过 LASSO 回归鉴定 SERPINA1、HSPA8、HSPB8、MAP1LC3A 和 DIRAS3 构成预后模型。高风险和低风险组患者的生存曲线具有统计学意义(P<0.05)。3 年和 5 年 ROC 显示,其 AUC 值分别达到 0.762 和 0.825。分期和风险评分是与预后相关的独立危险因素。RB1CC1、RPS6KB1 和 BIRC6 被鉴定为最主要的突变基因。结果表明,AGs 主要参与调节内肽酶的合成,并在 ErbB 信号通路中发挥重要作用。SERPIN1 与风险评分与分期密切相关(P<0.05);HSPA8 与风险评分与 T 分期密切相关(P<0.05);HSPB8 与 N 分期密切相关(P<0.05)。

结论

我们的预后模型对 40-60 岁患者的预后具有较强的预测能力。如果将分期加入到预后模型中,预测能力将更加强大。

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