研究工作表明长链非编码 RNA (lncRNA) 在透明细胞肾细胞癌 (ccRCC) 发病机制中的作用。 lncRNA HAGLR 在多种恶性肿瘤中进行了研究，但尚未在 ccRCC 中进行研究。根据肾透明细胞癌癌症基因组图谱 (TCGA-KIRC) 数据集，我们分析了 HAGLR 的分子改变，并构建了具有相关 miRNA 和 mRNA 的竞争性内源 RNA (ceRNA) 网络。进行基因本体分析以确定富含 HAGLR 回收 mRNA 的重要途径。评估了 HAGLR 和相关 mRNA 的临床重要性，并使用 TIMER 研究了所选 mRNA 编码基因对肿瘤免疫浸润的影响。 HAGLR 表达在 ccRCC 中比正常肾脏中降低，并且与基因启动子甲基化显着相关。肿瘤中低 HAGLR 水平显示出诊断效力，并且与临床病理学参数（分期/分级/转移）和患者生存率低相关。 HAGLR 相关的 ceRNA 网络由 TCGA-KIRC 数据集中差异表达的 13 个 miRNA 和 23 个 mRNA 组成。从 HAGLR 恢复的 mRNA 编码基因中，我们在训练数据集中开发了 5 个基因（PAQR5、ARHGAP24、HABP4、PDLIM5 和 RPS6KA2）预后特征，并在测试和整个数据集中对其进行了验证。特征基因的表达水平与免疫细胞的肿瘤浸润呈负相关，对ccRCC预后产生不利影响，并且还与促进浸润的肿瘤衍生趋化因子呈负相关。总之，HAGLR 似乎在 ccRCC 中发挥肿瘤抑制作用。 HAGLR 和相关基因特征可能有助于改善现有的预后措施并开发有效的 ccRCC 免疫治疗策略。© 2023。作者获得 Springer Science Business Media, LLC（Springer Nature 旗下子公司）的独家许可。

Research works suggested the role of long non-coding RNAs (lncRNAs) in pathogenesis of clear cell renal cell carcinoma (ccRCC). lncRNA HAGLR is studied in several malignancies, but not in ccRCC. From The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) dataset, we analyzed molecular alterations of HAGLR and constructed a competitive endogenous RNA (ceRNA) network with related miRNAs and mRNAs. Gene Ontology analysis was done to identify important pathways enriched with HAGLR recovered mRNAs. Clinical importance of HAGLR and related mRNAs was assessed and, the impact of selected mRNA-encoding genes on tumor immune infiltration was studied using TIMER. HAGLR expression was reduced in ccRCC than in normal kidneys, and correlated significantly with gene promoter methylation. Low HAGLR level in tumors showed diagnostic potency, and was associated with clinicopathological parameters (stage/grade/metastasis) and poor patient survival. The HAGLR-associated ceRNA network constituted 13 miRNAs and 23 mRNAs differentially expressed in the TCGA-KIRC dataset. From HAGLR recovered mRNA-encoding genes, we developed a 5-gene (PAQR5, ARHGAP24, HABP4, PDLIM5, and RPS6KA2) prognostic signature in the training dataset and validated it in testing as well as entire datasets. The expression level of signature genes showed negative correlation with tumor infiltration of immune cells having adverse impact on ccRCC prognosis and also with tumor derived chemokines facilitating the infiltration. In conclusion, HAGLR seemed to play a tumor suppressive role in ccRCC. HAGLR and associated gene signature may have implementation in improving existing prognostic measure and developing effective immunotherapeutic strategies for ccRCC.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.