Development of a Novel Autophagy-related Prognostic Signature for Serous Ovarian Cancer.
Development of a Novel Autophagy-related Prognostic Signature for Serous Ovarian Cancer.
复制标题
DOI：
10.7150/jca.25587
复制
发表时间：
2018
影响因子：
3.9
通讯作者：
Yang Q
中科院分区：
文献类型：
--
作者：
An Y;Bi F;You Y;Liu X;Yang Q
目的：大量证据表明，自噬在卵巢癌的生物学过程中起着至关重要的作用。本研究的目的是开发一种新的自噬相关的浆液性卵巢癌预后标志。研究方法：采用单变量考克斯比例回归模型分析mRNA微阵列和癌症基因组图谱（TCGA）中的临床数据，以筛选自噬相关的预后基因。多变量考克斯比例回归模型和生存分析用于开发八基因预后标记。多因素考克斯分析和分层分析表明，该标志是浆液性卵巢癌患者的独立预后因素。通过主成分分析和基因集富集分析（GSEA）研究了其生物信息学功能。最后，在浆液性卵巢癌中进一步分析了预后标志和基因突变状态之间的相关性，特别是关于BRCA 1和BRCA 2（BRCA 1/2）基因的突变状态。结果：自噬相关基因在正常卵巢组织和浆液性卵巢癌组织中的表达谱存在明显差异。我们分析了一组自噬相关基因，并确定了8个对浆液性卵巢癌具有重要预后价值的基因。随后，构建了自噬相关的卵巢癌风险特征，并根据其特征识别出预后不良的高风险或低风险患者。高风险患者的总生存期（OS）和无病生存期（DFS）时间明显短于低风险患者。GSEA结果表明，与低风险患者相比，高风险患者的自噬调节强度增强。当作为浆液性卵巢癌的独立预后因素进行研究时，在分层队列中可以看到该特征的显著预后价值。对于临床使用，我们开发了一个列线图，其中包括预后分类和七个临床风险因素。此外，我们确定了浆液性卵巢癌患者中发现的10个最常见的突变基因，并分析了它们在高风险和低风险患者中的差异。在293名患者中，62名患者有BRCA 1/2基因突变，这一结果与自噬相关的预后标志显著相关。结论：我们的研究结果表明，八基因自噬相关的签名可以作为浆液性卵巢癌病例的独立预后指标。
Purpose: Considerable evidence suggests that autophagy plays a crucial role in the biological processes of ovarian cancer. The aim of this study was to develop a novel autophagy-related prognostic signature for serous ovarian cancer. Methods: A univariate Cox proportional regression model was used to analyze mRNA microarray and clinical data in The Cancer Genome Atlas (TCGA) for the purpose of selecting autophagy-related prognostic genes. A multivariate Cox proportional regression model and the survival analysis were used to develop an eight-gene prognostic signature. The multivariate Cox and stratification analysis suggested that this signature was an independent prognostic factor for serous ovarian cancer patients. Bioinformatics functions were investigated by a principal components analysis and gene set enrichment analysis (GSEA). Finally, the correlation between the prognostic signature and gene mutation status was further analyzed in serous ovarian cancer, and especially with regard to the mutation status of BRCA1 and BRCA2 (BRCA1/2) genes. Results: Distinctly different autophagy-related gene expression profiles were identified in normal ovarian tissues and serous ovarian cancer tissues. We profiled an autophagy-related gene set and identified eight genes with significant prognostic values for serous ovarian cancer. Subsequently, an autophagy-related ovarian cancer risk signature was constructed, and patients at a high-risk or low-risk for poor prognosis were identified based on their signature. High-risk patients had significantly shorter overall survival (OS) and disease-free survival (DFS) times than low-risk patients. GSEA results suggested an enhanced intensity of autophagy regulation in high-risk patients when compared with low-risk patients. When studied as an independent prognostic factor for serous ovarian cancer, the significant prognostic value of this signature could be seen in the stratified cohorts. For clinical use, we developed a nomogram that included the prognostic classifier and seven clinical risk factors. Additionally, we identified the 10 most frequently mutated genes found in serous ovarian cancer patients, and analyzed them for their differences in high-risk and low-risk patients. Among 293 patients, 62 had BRCA1/2 gene mutations, and this result was significantly correlated with the autophagy-related prognostic signature. Conclusions: Our findings suggest that the eight-gene autophagy-related signature could serve as an independent prognostic indicator for cases of serous ovarian cancer.
登录
查看更多内容
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
--
作者：
Lili LN;Matyunina LV;Walker LD;Benigno BB;McDonald JF
通讯作者：
McDonald JF
影响因子：
10.5
作者：
Mathew, Robin;Kongara, Sameera;White, Eileen
通讯作者：
White, Eileen
影响因子：
10.5
作者：
Guo, Jessie Yanxiang;Chen, Hsin-Yi;White, Eileen
通讯作者：
White, Eileen
影响因子：
158.5
作者：
Lossos, IS;Czerwinski, DK;Levy, R
通讯作者：
Levy, R