Ling Xiaodong, Zhang Luquan, Fang Chengyuan, Liang Hao, Ma Jianqun
Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang, 150040, China.
Cancer Cell Int. 2024 Sep 9;24(1):310. doi: 10.1186/s12935-024-03497-w.
Phosphofructokinase P (PFKP) is a key rate-limiting enzyme in glycolysis, playing a crucial role in various pathophysiological processes. However, its specific function in tumors remains unclear. This study aims to evaluate the expression and specific role of PFKP across multiple tumor types (Pan-cancer) and to explore its potential clinical significance as a therapeutic target in cancer treatment.
We analyzed the expression of PFKP, immune cell infiltration, and patient prognosis across various cancers using data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Additionally, we conducted a series of experiments in lung cancer cells, including Western blot, CCK-8 assay, colony formation assay, transwell migration assay, scratch wound healing assay, LDH release assay, and flow cytometry, to evaluate the impact of PFKP on tumor cells.
PFKP was found to be highly expressed in most cancers and identified as a prognostic risk factor. Elevated PFKP expression is associated with poorer clinical outcomes, particularly in lung adenocarcinoma (LUAD). Receiver operating characteristic (ROC) curve analysis indicated that PFKP can effectively differentiate between cancerous and normal tissues. The expression of PFKP in most tumors showed significant correlations with tumor mutational burden (TMB), microsatellite instability (MSI), immune score, and immune cell infiltration. In vitro experiments demonstrated that PFKP overexpression promotes lung cancer cell proliferation and migration while inhibiting apoptosis, whereas PFKP deficiency results in the opposite effects.
PFKP acts as an oncogene involved in tumorigenesis and may influence the immune microenvironment within the tumor. Our findings suggest that PFKP could serve as a potential biomarker for predicting prognosis and the efficacy of immunotherapy in tumors.
磷酸果糖激酶P（PFKP）是糖酵解中的关键限速酶，在各种病理生理过程中起关键作用。然而，其在肿瘤中的具体功能仍不清楚。本研究旨在评估PFKP在多种肿瘤类型（泛癌）中的表达和特定作用，并探讨其作为癌症治疗中治疗靶点的潜在临床意义。
我们使用癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）的数据，分析了各种癌症中PFKP的表达、免疫细胞浸润和患者预后。此外，我们在肺癌细胞中进行了一系列实验，包括蛋白质免疫印迹法、CCK-8测定、集落形成测定、Transwell迁移测定、划痕伤口愈合测定、乳酸脱氢酶释放测定和流式细胞术，以评估PFKP对肿瘤细胞的影响。
发现PFKP在大多数癌症中高表达，并被确定为预后危险因素。PFKP表达升高与较差的临床结果相关，尤其是在肺腺癌（LUAD）中。受试者工作特征（ROC）曲线分析表明，PFKP可以有效区分癌组织和正常组织。PFKP在大多数肿瘤中的表达与肿瘤突变负担（TMB）、微卫星不稳定性（MSI）、免疫评分和免疫细胞浸润显著相关。体外实验表明，PFKP过表达促进肺癌细胞增殖和迁移，同时抑制细胞凋亡，而PFKP缺陷则产生相反的效果。
PFKP作为一种参与肿瘤发生的癌基因，可能影响肿瘤内的免疫微环境。我们的研究结果表明，PFKP可作为预测肿瘤预后和免疫治疗疗效的潜在生物标志物。
