Xie Jian, Peng Yang, Chen Xiaoyu, Li Qigang, Jian Bin, Wen Zelin, Liu Shengchun
Department of General Surgery, Yong Chuan Hospital of Chongqing Medical University, Chongqing, China.
Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
PLoS One. 2021 Jan 28;16(1):e0245908. doi: 10.1371/journal.pone.0245908. eCollection 2021.
This study aimed to find the prognostic value of Beta-lactamase-like (LACTB) in pancreatic adenocarcinoma (PAAD) patients. The mRNA expression of LACTB was upregulated in PAAD and was correlated with vital status (P = 0.0199). The immunoreactive scores of LACTB protein in human PAAD tissues were significantly higher than those in adjacent noncancerous pancreatic tissues. Receiver operating characteristic (ROC) curve assessment showed that LACTB mRNA expression has high diagnostic value in PAAD. Kaplan-Meier curve and Cox analyses suggested that patients with high LACTB mRNA expression have a poor prognosis, indicating that LACTB mRNA is an independent prognostic factor for overall survival [hazard ratio (HR) = 1.72, P = 0.015, 95% confidence interval (CI) = 1.106-2.253] and disease-specific survival (HR = 1.97, P = 0.004, 95% CI = 1.238-3.152) of PAAD patients. Gene set enrichment analysis (GSEA) revealed that hallmark_g2m_checkpoint, hallmark_myc_targets_v1, hallmark_e2f_targets, and kegg_cell_cycle were differentially enriched in phenotypes with high LACTB expression. In addition, CDC20, CDK4, MCM6, MAD2L1, MCM2 and MCM5 were leading genes intersecting in these four pathways, and a positive correlation between mRNA expression and LACTB was observed in most normal and cancer tissues. Finally, elevated LACTB mRNA expression was significantly related to multiple immune marker sets. Our results elucidate that LACTB is involved in the development of cancer, and that high LACTB expression in patients with PAAD can predict a poor prognosis. High LACTB expression was significantly correlated with cell cycle-related genes and multiple immune marker sets.
本研究旨在探寻β-内酰胺酶样蛋白（LACTB）在胰腺腺癌（PAAD）患者中的预后价值。LACTB的mRNA表达在PAAD中上调，且与生存状态相关（P = 0.0199）。人PAAD组织中LACTB蛋白的免疫反应评分显著高于相邻的非癌胰腺组织。受试者工作特征（ROC）曲线评估显示，LACTB mRNA表达在PAAD中具有较高的诊断价值。Kaplan-Meier曲线和Cox分析表明，LACTB mRNA表达高的患者预后较差，这表明LACTB mRNA是PAAD患者总生存[风险比（HR）= 1.72，P = 0.015，95%置信区间（CI）= 1.106 - 2.253]和疾病特异性生存（HR = 1.97，P = 0.004，95% CI = 1.238 - 3.152）的独立预后因素。基因集富集分析（GSEA）显示，在LACTB高表达的表型中，标志性_g2m_检查点、标志性_myc_靶标_v1、标志性_e2f_靶标和KEGG细胞周期存在差异富集。此外，细胞周期蛋白20（CDC20）、细胞周期蛋白依赖性激酶4（CDK4）、微小染色体维持蛋白6（MCM6）、有丝分裂后期促进复合物2（MAD2L1）、微小染色体维持蛋白2（MCM2）和微小染色体维持蛋白5（MCM5）是这四条通路中的关键基因，且在大多数正常组织和癌组织中观察到mRNA表达与LACTB呈正相关。最后，LACTB mRNA表达升高与多个免疫标志物集显著相关。我们的研究结果表明，LACTB参与癌症的发生发展，PAAD患者中LACTB高表达可预测预后不良。LACTB高表达与细胞周期相关基因和多个免疫标志物集显著相关。
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