Feng Lingsong, Ding Guodong, Zhou Yang, Zhu Haiyuan, Jiang Huiming
Department of Urology, Meizhou People's Hospital, Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou, People's Republic of China.
Pharmgenomics Pers Med. 2022 Oct 10;15:857-866. doi: 10.2147/PGPM.S382564. eCollection 2022.
Clear cell renal cell carcinoma (ccRCC), the most prevalent kidney cancer subtype, has a high mortality rate. Crystallin lambda 1 (CRYL1) encodes an enzyme that catalyzes the dehydrogenation of L-gulonate into dehydro-L-gulonate in uronate cycle. CRYL1 dysregulation has been linked to the progression of several cancers. This research aimed to evaluate the prognostic significance of CRYL1 expression in ccRCC prognosis.
Clinical data and gene expression profiles on ccRCC were retrieved from the University of California Santa Cruz Xena platform. Differences (variations) in the expression profiles of CRYL1 in ccRCC and healthy tissues were found using RNA-sequencing data, and these findings were validated using qPCR with real-world samples. CRYL1 expression levels were also linked to clinicopathological characteristics, survival, and immune microenvironments. The potential pathway via which CRYL1 expression levels impact the prognosis of patients with ccRCC was investigated using gene set enrichment analysis (GSEA).
In ccRCC tissues, CRYL1 expression levels were lower compared to healthy renal tissues in TCGA cohort (n = 535, < 0.001), which was validated in another real-world cohort (n = 14, < 0.001). Lower CRYL1 expression levels were linked to unfavorable clinicopathological characteristics and prognoses ( < 0.001). According to multivariate Cox regression analysis (P < 0.001), CRYL1 expression levels in patients with ccRCC could serve as an independent prognostic indicator. Furthermore, a strong link between CRYL1 expression levels and immune microenvironment was observed ( < 0.001). Finally, GSEA revealed that CRYL1 expression levels (P < 0.001) were associated with fatty acid metabolism, G2M checkpoint delays, and epithelial-mesenchymal transitions in ccRCC.
Our study found that lower levels of CRYL1 expression were linked to unfavorable clinicopathological characteristics and worse prognoses, and CRYL1 could serve as a new target for the treatment of ccRCC, which is useful for personalized medicine.
透明细胞肾细胞癌（ccRCC）是最常见的肾癌亚型，死亡率很高。晶状体蛋白λ1（CRYL1）编码一种酶，该酶在糖醛酸循环中催化L-古洛糖酸脱氢生成脱氢-L-古洛糖酸。CRYL1失调与多种癌症的进展有关。本研究旨在评估CRYL1表达在ccRCC预后中的预后意义。
从加利福尼亚大学圣克鲁兹分校Xena平台检索ccRCC的临床数据和基因表达谱。使用RNA测序数据发现ccRCC和健康组织中CRYL1表达谱的差异（变化），并使用qPCR对真实样本进行验证。CRYL1表达水平还与临床病理特征、生存率和免疫微环境相关。使用基因集富集分析（GSEA）研究CRYL1表达水平影响ccRCC患者预后的潜在途径。
在ccRCC组织中，TCGA队列（n = 535，P < 0.001）中CRYL1表达水平低于健康肾组织，这在另一个真实世界队列（n = 14，P < 0.001）中得到验证。较低的CRYL1表达水平与不良的临床病理特征和预后相关（P < 0.001）。根据多变量Cox回归分析（P < 0.001），ccRCC患者的CRYL1表达水平可作为独立的预后指标。此外，观察到CRYL1表达水平与免疫微环境之间存在密切联系（P < 0.001）。最后，GSEA显示CRYL1表达水平（P < 0.001）与ccRCC中的脂肪酸代谢、G2M检查点延迟和上皮-间质转化相关。
我们的研究发现，较低水平的CRYL1表达与不良的临床病理特征和较差的预后相关，CRYL1可作为ccRCC治疗的新靶点，这对个性化医疗有用。
