Kidney renal clear cell carcinoma (KIRC) is the subtype pf kidney cancer having the highest mortality as well as the highest potential of invasion and metastasis. The expression of HADH, encoding a key enzyme in fatty acid β-oxidation, has rarely been reported to correlate with prognosis and immune infiltration in cancers. This study aimed to explore the prognostic value of HADH in patients with KIRC. Gene expression profiles and clinical data of KIRC patients were acquired from The Cancer Genome Atlas. We compared the expression of HADH between KIRC tissues and normal tissues. Then, the relationship between HADH expression and the clinicopathological characteristics (survival, age, gender, stage, and grade) of KIRC was explored. Data from several online databases and paraffin-embedded specimens from two cohorts were used for external validation (10 cases from Meizhou People's Hospital and another 75 cases from a tissue chip, with both cohorts including KIRC samples and paired normal tissues). We also predicted the fractions of tumor-infiltrating immune cells (TIICs) in various tissues using CIBERSORT. Next, we estimated the prognostic value of differences in TIIC proportions between the high and low HADH expression groups. Finally, gene set enrichment analysis (GSEA) was performed to explore the potential mechanisms by which HADH expression influences patient survival. The expression of HADH was significantly lower in KIRC tissue than in normal tissue. Decreased expression of HADH was significantly correlated with high histologic grade, advanced stage, and poor prognosis. The differential expression of HADH was validated at the protein level by immunohistochemistry. Multivariate Cox regression analysis indicated that HADH was an independent prognostic factor for KIRC. In addition, HADH expression was significantly associated with the accumulation of several TIICs, especially regulatory T cells. Finally, GSEA revealed that the transcriptome of the low HADH expression group was significantly enriched in genes involved in not only epithelial-mesenchymal transition and inflammatory response but also TNF-α, IL-6-JAK-STAT3, and interferon-γ signaling. In conclusion, our study demonstrated that decreased expression of HADH is related to poor prognosis and immune infiltration in KIRC; this finding may provide crucial information for the development of immunotherapies.

肾肾透明细胞癌（KIRC）是肾癌中死亡率最高、侵袭转移潜力最高的亚型 pf 肾癌。HADH的表达，编码脂肪酸 β 氧化的关键酶，很少被报道与癌症的预后和免疫浸润相关。本研究旨在探讨HADH在 KIRC 患者中的预后价值。KIRC 患者的基因表达谱和临床数据来自 The Cancer Genome Atlas。我们比较了KIRC组织和正常组织之间 HADH 的表达。那么，HADH之间的关系探讨了KIRC的表达和临床病理特征（生存期、年龄、性别、分期和分级）。来自多个在线数据库的数据和来自两个队列的石蜡包埋样本用于外部验证（10 例来自梅州人民医院，另外 75 例来自组织芯片，​​两个队列都包括 KIRC 样本和配对的正常组织）。我们还使用 CIBERSORT 预测了各种组织中肿瘤浸润性免疫细胞 (TIIC) 的分数。接下来，我们估计了高和低HADH表达组之间 TIIC 比例差异的预后价值。最后，进行基因集富集分析 (GSEA) 以探索HADH表达影响患者生存的潜在机制。的表达KIRC组织中的 HADH 显着低于正常组织。HADH表达降低与高组织学分级、晚期和预后不良显着相关。通过免疫组织化学在蛋白质水平上验证了HADH的差异表达。多变量 Cox 回归分析表明HADH是 KIRC 的独立预后因素。此外，HADH表达与几种 TIIC 的积累显着相关，尤其是调节性 T 细胞。最后，GSEA 揭示了低HADH的转录组表达组显着富集的基因不仅参与上皮-间质转化和炎症反应，还参与TNF-α、IL-6-JAK-STAT3和干扰素-γ信号传导。总之，我们的研究表明，HADH 的表达降低与KIRC的不良预后和免疫浸润有关。这一发现可能为免疫疗法的发展提供重要信息。