Department of Endoscopy, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
J Proteome Res. 2022 Mar 4;21(3):740-746. doi: 10.1021/acs.jproteome.1c00607. Epub 2021 Nov 24.
Branched-chain amino acid (BCAA) metabolism plays an important role in the pancreatic carcinogenesis, but its mechanism remains unclear. Hence, this study was performed to investigate the value of genes related to BCAA catabolism in pancreatic cancer. The online Gene Expression Omnibus database, The Cancer Genome Atlas, and International Cancer Genome Consortium data sets were searched for bioinformatic analysis. Univariate Cox and Lasso regression were applied to construct a predictive model. Human cancer cell lines and tissue microarray (TMA) were applied for validation. From the 48 BCAA-catabolism enzyme (BCE) genes, a 5-gene risk-score (ABAT, ACAT1, BCAT1, BCAT2, and DBT) was constructed. Patients in high-risk and low-risk groups stratified by risk-score indicated significantly different overall survival. Given the clinical parameters, the risk-score was an independent predictor for prognosis. Among the five genes, BCAT2 and ABAT were hub genes with favorable prognosis value, which was validated by TMA immunohistochemistry (IHC) staining. Immune infiltration analysis indicated high-risk group enriched macrophage, and decreased positive cell density of stromal CD68 macrophage in TMA was observed for BCAT2 with low-expression versus high-expression cases. In conclusion, a risk-score involving five BCE genes was proposed to predict the poor prognosis of pancreatic cancer. On the basis of the immune infiltration analysis, the underlying mechanism might be BCAT2 associated stromal macrophage infiltration.
支链氨基酸（BCAA）代谢在胰腺癌发生中起着重要作用，但其中的机制仍不清楚。因此，本研究旨在探讨与 BCAA 分解代谢相关的基因在胰腺癌中的价值。在线基因表达综合数据库、癌症基因组图谱和国际癌症基因组联合会数据库中进行了生物信息学分析。单变量 Cox 和 Lasso 回归被用于构建预测模型。人类癌细胞系和组织微阵列（TMA）用于验证。从 48 个 BCAA 分解代谢酶（BCE）基因中，构建了一个 5 个基因风险评分（ABAT、ACAT1、BCAT1、BCAT2 和 DBT）。按风险评分分层的高危和低危组患者的总生存率有显著差异。在考虑了临床参数后，风险评分是独立的预后预测因子。在这 5 个基因中，BCAT2 和 ABAT 是具有良好预后价值的枢纽基因，这通过 TMA 免疫组化（IHC）染色得到了验证。免疫浸润分析表明，高危组富含巨噬细胞，并且在 BCAT2 低表达与高表达病例中，观察到基质 CD68 巨噬细胞的阳性细胞密度降低。总之，提出了一个涉及 5 个 BCE 基因的风险评分来预测胰腺癌的不良预后。基于免疫浸润分析，其潜在机制可能与 BCAT2 相关的基质巨噬细胞浸润有关。
