Zhang Jing, Xiang Honglin, Jiang Ling, Wang Mei, Yang Guodong
Department of Gastroenterology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.
Department of Orthopaedics, Laboratory of Biological Tissue Engineering and Digital Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.
Oncol Lett. 2024 Oct 4;28(6):592. doi: 10.3892/ol.2024.14725. eCollection 2024 Dec.
Platelet activity in the tumor microenvironment (TME) is crucial for the development of tumors. However, the roles and clinical potential of platelet activity in the TME for virus-related hepatocellular carcinoma (HCC) remain unclear. The present study aimed to identify a novel signature based on platelet activity for prognostic prediction and treatment decisions in virus-related HCC. First, a novel platelet signature score (PSS) for each patient with virus-related HCC from The Cancer Genome Atlas was calculated using gene set variation analysis, and the patients were divided into two subgroups (high and low PSS). It was demonstrated that the patients with a high PSS had a worse prognosis, higher platelet activity, stronger inflammation and immunosuppression in TME than patients with a low PSS. Furthermore, 137 differentially expressed genes (DEGs; fold change >2; P<0.05) were identified using 'DESeq2' and 'edgeR' software. Subsequently, 3 genes (cyclin-J-Like protein, nuclear receptor subfamily 0 group B member 1 and tripartite motif containing 54) were identified from DEGs using univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses. Risk score (RS) was calculated based on gene expression and coefficients from LASSO. Patients were divided into high and low RS groups according to the median value, and the 3-gene model was used to predict prognoses and drug responses. Notably, it was demonstrated that patients with a low RS may be better candidates for immune therapy due to lower levels of tumor immune dysfunction and exclusion scores. Moreover, patients with a high RS may be better candidates for nonimmune therapy due to lower half-maximal inhibitory concentration values of drugs (such as AKT inhibitors and gemcitabine). Finally, it was demonstrated that patients with a high PSS and RS had a higher platelet activity, inflammation status, tumor hallmarks and the worst prognosis than patients with a low PSS and RS. This helped to better find patients with these characteristics and suitable treatments using this method. Collectively, the findings of the present study indicate that PSS combined with RS has great potential to evaluate the prognosis of patients with virus -related HCC and assist in deciding treatment strategies.
肿瘤微环境（TME）中的血小板活性对肿瘤的发展至关重要。然而，血小板活性在TME中对病毒相关肝细胞癌（HCC）的作用和临床潜力仍不清楚。本研究旨在基于血小板活性确定一种新的特征，用于病毒相关HCC的预后预测和治疗决策。首先，使用基因集变异分析计算来自癌症基因组图谱的每位病毒相关HCC患者的新型血小板特征评分（PSS），并将患者分为两个亚组（高PSS和低PSS）。结果表明，高PSS患者的预后较差，血小板活性较高，TME中的炎症和免疫抑制作用比低PSS患者更强。此外，使用“DESeq2”和“edgeR”软件鉴定出137个差异表达基因（DEG；倍数变化>2；P<0.05）。随后，使用单变量Cox和最小绝对收缩和选择算子（LASSO）分析从DEG中鉴定出3个基因（细胞周期蛋白J样蛋白、核受体亚家族0 B组成员1和含三联基序54）。根据基因表达和LASSO系数计算风险评分（RS）。根据中位数将患者分为高RS组和低RS组，并使用三基因模型预测预后和药物反应。值得注意的是，结果表明，低RS患者由于肿瘤免疫功能障碍和排除评分较低，可能是免疫治疗的更好候选者。此外，高RS患者由于药物（如AKT抑制剂和吉西他滨）的半数最大抑制浓度值较低，可能是非免疫治疗的更好候选者。最后，结果表明，高PSS和RS患者比低PSS和RS患者具有更高的血小板活性、炎症状态、肿瘤特征和最差的预后。这有助于使用该方法更好地找到具有这些特征的患者和合适的治疗方法。总的来说，本研究结果表明，PSS与RS相结合在评估病毒相关HCC患者的预后和协助决定治疗策略方面具有巨大潜力。
