肾细胞癌(RCC)是最常见的肾脏恶性肿瘤之一。对临床诊断和治疗提出了重大挑战。巨噬细胞在RCC中起着至关重要的作用,促进肿瘤进展,需要进一步研究。以前的研究已经确定LHFPL2是一种与生殖相关的跨膜蛋白,但其与肿瘤或巨噬细胞的关系尚未讨论。这项研究利用TCGA数据库中609名KIRC患者的转录组测序数据和34,326个肾癌细胞的单细胞测序数据进行后续分析。我们综合评价了LHFPL2的表达及其与临床特征的关系,肿瘤预后,免疫浸润,和突变。此外,我们使用单细胞数据进一步评估了LHFPL2与巨噬细胞M2极化之间的相关性,并通过分子对接探索了其作为癌症治疗靶点的潜力.结果表明,LHFPL2在RCC中上调,并与低生存率相关。在临床分期中,高LHFPL2组的恶性和高转移患者比例高于低LHFPL2组.此外,我们发现LHFPL2影响RCC免疫浸润,其表达与各种免疫检查点和M2相关基因表达呈正相关,与M2巨噬细胞浸润呈正相关,与活化的NK细胞呈负相关。此外,LHFPL2在巨噬细胞中显示出特异性表达,高表达亚组表现出更高的M2极化,缺氧,免疫逃避,和血管生成评分,促进肿瘤进展。最后,我们预测了几种靶向LHFPL2的潜在药物,如科尼伐普坦和尼洛替尼.我们的分析详细描绘了LHFPL2在肿瘤微环境中的免疫特征及其与巨噬细胞M2极化的正相关性,为肿瘤免疫治疗提供新的见解。我们还提出了针对该基因的潜在FDA批准的药物,应该在未来的研究中测试它们与LHFPL2的结合作用。
Renal cell carcinoma (RCC) is one of the most common malignant tumors of the kidney, presenting significant challenges for clinical diagnosis and treatment. Macrophages play crucial roles in RCC, promoting tumor progression and warranting further investigation. Previous studies have identified LHFPL2 as a transmembrane protein associated with reproduction, but its relationship with tumors or macrophages has not been discussed. This study utilized transcriptomic sequencing data from 609 KIRC patients in the TCGA database and single-cell sequencing data from 34,326 renal carcinoma cells for subsequent analysis. We comprehensively evaluated the expression of LHFPL2 and its relationship with clinical features, tumor prognosis, immune infiltration, and mutations. Additionally, we further assessed the correlation between LHFPL2 and macrophage M2 polarization using single-cell data and explored its potential as a cancer therapeutic target through molecular docking. The results demonstrated that LHFPL2 is upregulated in RCC and associated with poor survival rates. In clinical staging, the proportion of malignant and high-metastasis patients was higher in the high-LHFPL2 group than in the low-LHFPL2 group. Furthermore, we found that LHFPL2 influences RCC immune infiltration, with its expression positively correlated with various immune checkpoint and M2-related gene expressions, positively associated with M2 macrophage infiltration, and negatively correlated with activated NK cells. Moreover, LHFPL2 showed specific expression in macrophages, with the high-expression subgroup exhibiting higher M2 polarization, hypoxia, immune evasion, and angiogenesis scores, promoting tumor progression. Finally, we predicted several potential drugs targeting LHFPL2, such as conivaptan and nilotinib. Our analysis elaborately delineates the immune characteristics of LHFPL2 in the tumor microenvironment and its positive correlation with macrophage M2 polarization, providing new insights into tumor immunotherapy. We also propose potential FDA-approved drugs targeting this gene, which should be tested for their binding effects with LHFPL2 in future studies.