Zhao Yan, Xu Xu, Wang Yue, Wu Lin D, Luo Rui L, Xia Ren P
Department of Organ Transplantation, Kunming Medical University First Affiliated Hospital, Kunming, China.
Department of Urology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China.
Front Oncol. 2023 Jun 26;13:1197898. doi: 10.3389/fonc.2023.1197898. eCollection 2023.
Tumor purity takes on critical significance to the progression of solid tumors. The aim of this study was at exploring potential prognostic genes correlated with tumor purity in hepatocellular carcinoma (HCC) by bioinformatics analysis.
The ESTIMATE algorithm was applied for determining the tumor purity of HCC samples from The Cancer Genome Atlas (TCGA). The tumor purity-associated genes with differential expression (DEGs) were identified based on overlap analysis, weighted gene co-expression network analysis (WGCNA), and differential expression analysis. The prognostic genes were identified in terms of the prognostic model construction based on the Kaplan-Meier (K-M) survival analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses. The expression of the above-described genes was further validated by the GSE105130 dataset from the Gene Expression Omnibus (GEO) database. We also characterized the clinical and immunophenotypes of prognostic genes. Gene set enrichment analysis (GSEA) was carried out for exploring the biological signaling pathway.
A total of 26 tumor purity-associated DEGs were identified, which were involved in biological processes such as immune/inflammatory responses and fatty acid elongation. Ultimately, we identified ADCK3, HK3, and PPT1 as the prognostic genes for HCC. Moreover, HCC patients exhibiting higher ADCK3 expression and lower HK3 and PPT1 expressions had a better prognosis. Furthermore, high HK3 and PPT1 expressions and low ADCK3 expression resulted in high tumor purity, high immune score, high stromal score, and high ESTIMATE score. GSEA showed that the abovementioned prognostic genes showed a significant correlation with immune-inflammatory response, tumor growth, and fatty acid production/degradation.
In conclusion, this study identified novel predictive biomarkers (ADCK3, HK3, and PPT1) and studied the underlying molecular mechanisms of HCC pathology initially.
肿瘤纯度对实体瘤的进展具有至关重要的意义。本研究旨在通过生物信息学分析探索与肝细胞癌（HCC）肿瘤纯度相关的潜在预后基因。
应用ESTIMATE算法确定来自癌症基因组图谱（TCGA）的HCC样本的肿瘤纯度。基于重叠分析、加权基因共表达网络分析（WGCNA）和差异表达分析，鉴定出具有差异表达（DEG）的肿瘤纯度相关基因。基于Kaplan-Meier（K-M）生存分析和最小绝对收缩和选择算子（LASSO）回归分析构建预后模型，从而鉴定出预后基因。通过来自基因表达综合数据库（GEO）的GSE105130数据集进一步验证上述基因的表达。我们还对预后基因的临床和免疫表型进行了表征。进行基因集富集分析（GSEA）以探索生物信号通路。
共鉴定出26个与肿瘤纯度相关的DEG，它们参与免疫/炎症反应和脂肪酸延长等生物学过程。最终，我们鉴定出ADCK3、HK3和PPT1作为HCC的预后基因。此外，ADCK3表达较高且HK3和PPT1表达较低的HCC患者预后较好。此外，HK3和PPT1高表达以及ADCK3低表达导致肿瘤纯度高、免疫评分高、基质评分高和ESTIMATE评分高。GSEA表明，上述预后基因与免疫炎症反应、肿瘤生长和脂肪酸产生/降解显著相关。
总之，本研究鉴定出了新的预测生物标志物（ADCK3、HK3和PPT1），并初步研究了HCC病理的潜在分子机制。
