Lu Xiangyun, Pei Yuhui, Peng Hao, Li Man, Li Jing, Yao Yongkun, Wang Lianghai
NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital/School of Medicine, Shihezi University, Shihezi, Xinjiang, China.
Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China.
World J Surg Oncol. 2025 Jun 9;23(1):225. doi: 10.1186/s12957-025-03879-y.
Esophageal squamous cell carcinoma (ESCC) is a common tumor characterized by a poor prognosis. PINK1 is strongly associated with tumorigenesis. However, the role of PINK1 in the progression of ESCC has not been elucidated.
The expression levels of PINK1 in tumor samples and corresponding normal tissues were evaluated using RNA-sequencing and gene expression array datasets. Pathway enrichment and immune infiltration analyses were performed to explore the role of PINK1 in ESCC development. Subsequently, cell counting kit-8, colony-forming assay, and Transwell assays were implemented to measure the proliferation and motility of ESCC cells. The glucose, ATP, pyruvate, and lactate concentrations were measured using suitable assay kits.
PINK1 expression was significantly lower in ESCC samples across independent cohorts. In vitro assays demonstrated that PINK1 could inhibit the proliferation, migration, and invasive capabilities of ESCC cells. Furthermore, PINK1 could decrease intracellular glucose, lactic acid, pyruvic acid, and ATP levels in ESCC cells, whereas the glycolytic inhibitor 2-DG could abrogate its effect. Additionally, immunosuppressive-related gene sets were enriched in the PINK1 low-expression group. Immune infiltration analysis revealed that PINK1 expression was positively correlated with dendritic cells and T helper 1 cells within the tumor microenvironment.
PINK1 inhibits cell growth, movement, glycolysis, and immune activation in ESCC, making it a promising therapeutic target.
食管鳞状细胞癌（ESCC）是一种常见肿瘤，预后较差。PINK1与肿瘤发生密切相关。然而，PINK1在ESCC进展中的作用尚未阐明。
利用RNA测序和基因表达阵列数据集评估肿瘤样本及相应正常组织中PINK1的表达水平。进行通路富集和免疫浸润分析以探讨PINK1在ESCC发生发展中的作用。随后，采用细胞计数试剂盒-8、集落形成试验和Transwell试验检测ESCC细胞的增殖和运动能力。使用合适的检测试剂盒测量葡萄糖、ATP、丙酮酸和乳酸浓度。
在独立队列的ESCC样本中，PINK1表达显著降低。体外试验表明，PINK1可抑制ESCC细胞的增殖、迁移和侵袭能力。此外，PINK1可降低ESCC细胞内葡萄糖、乳酸、丙酮酸和ATP水平，而糖酵解抑制剂2-DG可消除其作用。此外，免疫抑制相关基因集在PINK1低表达组中富集。免疫浸润分析显示，PINK1表达与肿瘤微环境中的树突状细胞和辅助性T细胞1呈正相关。
PINK1抑制ESCC中的细胞生长、运动、糖酵解和免疫激活，使其成为一个有前景的治疗靶点。
