Kim Chi Young, Lee Eun Hye, Kwak Se Hyun, Lee Sang Hoon, Kim Eun Young, Park Min Kyoung, Cha Yoon Jin, Chang Yoon Soo
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Tuberc Respir Dis (Seoul). 2024 Oct;87(4):494-504. doi: 10.4046/trd.2023.0166. Epub 2024 Aug 16.
Ubiquitin C-terminal hydrolase L1 (UCHL1), which encodes thiol protease that hydrolyzes a peptide bond at the C-terminal glycine residue of ubiquitin, regulates cell differentiation, proliferation, transcriptional regulation, and numerous other biological processes and may be involved in lung cancer progression. UCHL1 is mainly expressed in the brain and plays a tumor-promoting role in a few cancer types; however, there are limited reports regarding its role in lung cancer.
Single-cell RNA (scRNA) sequencing using 10X chromium v3 was performed on a paired normal-appearing and tumor tissue from surgical specimens of a patient who showed unusually rapid progression. To validate clinical implication of the identified biomarkers, immunohistochemical (IHC) analysis was performed on 48 non-small cell lung cancer (NSCLC) tissue specimens, and the correlation with clinical parameters was evaluated.
We identified 500 genes overexpressed in tumor tissue compared to those in normal tissue. Among them, UCHL1, brain expressed X-linked 3 (BEX3), and midkine (MDK), which are associated with tumor growth and progression, exhibited a 1.5-fold increase in expression compared to that in normal tissue. IHC analysis of NSCLC tissues showed that only UCHL1 was specifically overexpressed. Additionally, in 48 NSCLC specimens, UCHL1 was specifically upregulated in the cytoplasm and nuclear membrane of tumor cells. Multivariable logistic analysis identified several factors, including smoking, tumor size, and high-grade dysplasia, to be typically associated with UCHL1 overexpression. Survival analyses using The Cancer Genome Atlas (TCGA) datasets revealed that UCHL1 overexpression is substantially associated with poor survival outcomes. Furthermore, a strong association was observed between UCHL1 expression and the clinicopathological features of patients with NSCLC.
UCHL1 overexpression was associated with smoking, tumor size, and high-grade dysplasia, which are typically associated with a poor prognosis and survival outcome. These findings suggest that UCHL1 may serve as an effective biomarker of NSCLC.
泛素 C 末端水解酶 L1（UCHL1）编码硫醇蛋白酶，该酶可水解泛素 C 末端甘氨酸残基处的肽键，调节细胞分化、增殖、转录调控及许多其他生物学过程，可能参与肺癌进展。UCHL1 主要在大脑中表达，在少数癌症类型中发挥促肿瘤作用；然而，关于其在肺癌中的作用报道有限。
对一名进展异常迅速的患者手术标本中的配对正常外观组织和肿瘤组织进行了使用 10X 铬 v3 的单细胞 RNA（scRNA）测序。为验证所鉴定生物标志物的临床意义，对 48 例非小细胞肺癌（NSCLC）组织标本进行了免疫组织化学（IHC）分析，并评估了其与临床参数的相关性。
与正常组织相比，我们在肿瘤组织中鉴定出 500 个过表达基因。其中，与肿瘤生长和进展相关的 UCHL1、脑表达 X 连锁 3（BEX3）和中期因子（MDK），其表达较正常组织增加了 1.5 倍。NSCLC 组织的 IHC 分析表明，只有 UCHL1 特异性过表达。此外，在 48 例 NSCLC 标本中，UCHL1 在肿瘤细胞的细胞质和核膜中特异性上调。多变量逻辑分析确定了包括吸烟、肿瘤大小和高级别发育异常等几个因素通常与 UCHL1 过表达相关。使用癌症基因组图谱（TCGA）数据集进行的生存分析显示，UCHL1 过表达与不良生存结果显著相关。此外，观察到 UCHL1 表达与 NSCLC 患者的临床病理特征之间存在密切关联。
UCHL1 过表达与吸烟、肿瘤大小和高级别发育异常相关，这些通常与预后不良和生存结果相关。这些发现表明，UCHL1 可能作为 NSCLC 的有效生物标志物。
