Yao Yiyang, Zhu Tong, Shen Xiaoyi, Ma Junyong, Zhu Xudong, Jiang Jie
Department of Gastroenterology, Qidong People's Hospital, Nantong, People's Republic of China.
Department of Breast Surgery, Panjin Central Hospital, Panjin, People's Republic of China.
Int J Gen Med. 2025 Jul 16;18:3933-3950. doi: 10.2147/IJGM.S490019. eCollection 2025.
Lysosomes play an important role in the pathological processes of cancer development. However, its effects on the prognosis and tumor microenvironment of hepatocellular carcinoma (HCC) remain unclear. Therefore, we aim to explore the novel molecular subtypes of HCC via lysosome-related genes (LRGs) for prognosis and therapy prediction in this study.
Using the data of TCGA, differential expression and survival analyses were performed. Consequently, 109 key LRGs were obtained and 374 HCC samples were clustered into two groups: C1 and C2. A three-gene prognostic prediction nomogram was constructed using WCGNA and Cox regression analyses. Furthermore, pathway enrichment conditions, immune infiltration, immune checkpoint expression, and drug sensitivity were analyzed for the two subtypes. RT-qPCR was also used to validate the expression of the selected key LRGs.
Key LRGs were highly expressed in the C1 subtype, and their prognosis was worse. The degree of immune cell infiltration and pathway enrichment results were also significantly different between the two subtypes. Furthermore, the three-gene prognostic prediction nomogram including LAPTM4B, PRKCD and LPCAT1, had a relatively high prognostic prediction ability. Meanwhile, the expression of immune checkpoints, human leukocyte antigen, and TIDE score were higher in the C1 subtype, suggesting that immune evasion was more likely to occur in this subtype. Drug sensitivity analysis showed that several drugs were more sensitive to C1 subtypes and might serve as drug candidates for these patients.
We identified two novel molecular subtypes of HCC based on LRGs, and found that the LRGs related subtypes demonstrated significant efficacy in predicting the prognosis and therapeutic outcomes for patients with HCC. Moreover, a novel prognostic prediction nomogram was also developed, which possessed excellent prognostic prediction capabilities. We hope the novel LRG-related subtypes and nomogram of HCC would provide new insights and guidelines for clinical practice in the future.
溶酶体在癌症发展的病理过程中起重要作用。然而，其对肝细胞癌（HCC）预后和肿瘤微环境的影响仍不清楚。因此，在本研究中，我们旨在通过溶酶体相关基因（LRGs）探索HCC的新型分子亚型，用于预后和治疗预测。
利用TCGA的数据进行差异表达和生存分析。结果，获得了109个关键LRGs，并将374例HCC样本聚类为两组：C1和C2。使用WCGNA和Cox回归分析构建了一个三基因预后预测列线图。此外，还分析了两种亚型的通路富集情况、免疫浸润、免疫检查点表达和药物敏感性。RT-qPCR也用于验证所选关键LRGs的表达。
关键LRGs在C1亚型中高表达，其预后较差。两种亚型之间的免疫细胞浸润程度和通路富集结果也有显著差异。此外，包括LAPTM4B、PRKCD和LPCAT1的三基因预后预测列线图具有相对较高的预后预测能力。同时，C1亚型中免疫检查点、人类白细胞抗原的表达和TIDE评分较高，表明该亚型更易发生免疫逃逸。药物敏感性分析表明，几种药物对C1亚型更敏感，可能作为这些患者的候选药物。
我们基于LRGs鉴定出两种新型HCC分子亚型，发现与LRGs相关的亚型在预测HCC患者的预后和治疗结果方面具有显著效果。此外，还开发了一种新型预后预测列线图，具有出色的预后预测能力。我们希望HCC的新型LRG相关亚型和列线图能为未来的临床实践提供新的见解和指导。
