目的:RNA结合蛋白(RBPs)在肿瘤的发生和免疫治疗中起关键作用。富含亮氨酸的五肽重复蛋白(LRPPRC)对于RNA多聚腺苷酸化至关重要,运输,和稳定性。尽管最近的研究表明LRPPRC在肿瘤进展中的潜在作用,其在肿瘤预后中的意义,诊断,免疫学仍不清楚。
方法:我们使用各种数据库全面分析了LRPPRC在肿瘤中的表达,包括人类转录组细胞图谱(HTCA),加州大学圣克鲁斯分校(UCSC),人蛋白质图谱(HPA),Sangerbox,TISIB,遗传狂躁症,GSCALite,还有CellMiner.我们检查了LRPPRC表达水平与预后之间的相关性,免疫浸润,免疫疗法,甲基化,生物学功能,和药物敏感性。使用肿瘤免疫单细胞集线器(TISCH)和CancerSEA软件进行单细胞分析。根据LRPPRC水平对急性髓细胞性白血病(AML)患者进行功能和免疫浸润分析。使用体外实验验证了LRPPRC在癌症中的作用。
结果:我们的研究结果表明,LRPPRC在几乎所有癌症类型中都高表达,表明其显著的预后和诊断潜力。值得注意的是,LRPPRC与多种免疫特征相关,如免疫细胞浸润,免疫检查点基因,肿瘤突变负担,和微卫星不稳定,表明其在指导免疫治疗策略方面的价值。在AML中,高表达组的免疫细胞水平较低,包括CD8+T细胞。体外实验证实了LRPPRC敲低对AML细胞增殖的抑制作用。
结论:本研究强调LRPPRC是一种可靠的泛癌症预后和免疫生物标志物,特别是AML。这为LRPPRC靶向癌症治疗的未来研究奠定了基础。
OBJECTIVE: RNA-binding proteins (RBPs) play pivotal roles in carcinogenesis and immunotherapy. Leucine-rich pentapeptide repeat-containing protein (LRPPRC) is crucial for RNA polyadenylation, transport, and stability. Although recent studies have suggested LRPPRC\'s potential role in tumor progression, its significance in tumor prognosis, diagnosis, and immunology remains unclear.
METHODS: We comprehensively analyzed LRPPRC expression in tumors using various databases, including Human Transcriptome Cell Atlas (HTCA), University of California Santa Cruz (UCSC), Human Protein Atlas (HPA), Sangerbox, TISIDB, GeneMANIA, GSCALite, and CellMiner. We examined the correlation between LRPPRC expression level and prognosis, immune infiltration, immunotherapy, methylation, biological function, and drug sensitivity. Single-cell analysis was performed using Tumor Immune Single Cell Hub (TISCH) and CancerSEA software. Patients with acute myeloid leukemia (AML) were categorized based on LRPPRC levels for functional and immune infiltration analyses. The role of LRPPRC in cancer was validated using in vitro experiments.
RESULTS: Our findings revealed that LRPPRC was highly expressed in almost all cancer types, indicating its significant prognostic and diagnostic potential. Notably, LRPPRC was associated with diverse immune features, such as immune cell infiltration, immune checkpoint genes, tumor mutational burden, and microsatellite instability, suggesting its value in guiding immunotherapy strategies. Within AML, the high-expression group had lower levels of immune cells, including CD8+ T cells. In vitro experiments confirmed the inhibitory effects of LRPPRC knockdown on AML cell proliferation.
CONCLUSIONS: This study highlights LRPPRC as a reliable pan-cancer prognostic and immune biomarker, particularly in AML. It lays the groundwork for future research on LRPPRC-targeted cancer therapies.