Sun Dawei, Duan Xiaohong, Li Ning, Qiao Ou, Hou Yingjie, Ma Zihuan, Liu Siyao, Gong Yanhua, Liu Zichuan
School of Disaster and Emergency Medicine, Faculty of Medicine, Tianjin University, No. 92 Weijin Road, Nankai District, Tianjin, 300072, China.
Institute of Disaster and Emergency Medicine, Faculty of Medicine, Tianjin University, Tianjin, China.
Sci Rep. 2025 Apr 6;15(1):11787. doi: 10.1038/s41598-025-92177-4.
Lung adenocarcinoma is the most prevalent lung cancer type. Ubiquitination, a critical post-translational modification process that regulates protein degradation and signaling pathways, has been implicated in various cancers, including LUAD. We aimed to explore the associations between ubiquitination and lung adenocarcinoma. TCGA-LUAD cohort served as the training set. Unsupervised clustering, univariate Cox regression, Random Survival Forests, and least absolute shrinkage and selection operator (LASSO) Cox regression were applied to identify ubiquitination-related genes (URGs), then ubiquitination-related risk scores (URRS) were calculated using gene expression and the univariate Cox's coefficient. Comparisons between the high and the low URRS group regarding chemotherapy drug response, immune infiltration level, tumor mutation burden (TMB), tumor neoantigen load (TNB), PD1/L1 expression, and enriched pathways were performed. URRS was calculated based on the expression of DTL, UBE2S, CISH, and STC1. Patients with higher URRS had a worse prognosis (Hazard Ratio [HR] = 0.54, 95% Confidence Interval [CI]: 0.39-0.73, p < 0.001), and the prognosis of the URRS was further confirmed in 6 external validation cohorts (Hazard Ratio [HR] = 0.58, 95% Confidence Interval [CI]: 0.36-0.93, p = 0.023). The high URRS group had higher PD1/L1 expression level (p < 0.05), TMB (p < 0.001), TNB (p < 0.001), and TME scores (p < 0.001). The IC50 values of various chemotherapy drugs were lower in the high URRS group. In addition, we found that upregulation of STC1, UBE2S, and DTL was associated with worse, while upregulation of CISH was associated with better prognosis. We also performed a reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for validation. In conclusion, the ubiquitination-based signature might serve as a biomarker to help evaluate the prognosis, biological features, and appropriate treatment for patients with lung adenocarcinoma.
肺腺癌是最常见的肺癌类型。泛素化是一种关键的翻译后修饰过程，可调节蛋白质降解和信号通路，已被证明与包括肺腺癌在内的多种癌症有关。我们旨在探讨泛素化与肺腺癌之间的关联。TCGA-LUAD队列用作训练集。应用无监督聚类、单变量Cox回归、随机生存森林和最小绝对收缩和选择算子（LASSO）Cox回归来识别泛素化相关基因（URG），然后使用基因表达和单变量Cox系数计算泛素化相关风险评分（URRS）。对高URRS组和低URRS组在化疗药物反应、免疫浸润水平、肿瘤突变负担（TMB）、肿瘤新抗原负荷（TNB）、PD1/L1表达和富集通路方面进行比较。URRS是根据DTL、UBE2S、CISH和STC1的表达计算得出的。URRS较高的患者预后较差（风险比[HR]=0.54，95%置信区间[CI]：0.39-0.73，p<0.001），并且在6个外部验证队列中进一步证实了URRS的预后情况（风险比[HR]=0.58，95%置信区间[CI]：0.36-0.93，p=0.023）。高URRS组具有更高的PD1/L1表达水平（p<0.05）、TMB（p<0.001）、TNB（p<0.001）和肿瘤微环境（TME）评分（p<0.001）。高URRS组中各种化疗药物的半数抑制浓度（IC50）值较低。此外，我们发现STC1、UBE2S和DTL的上调与较差的预后相关，而CISH的上调与较好的预后相关。我们还进行了逆转录定量聚合酶链反应（RT-qPCR）以进行验证。总之，基于泛素化的特征可能作为一种生物标志物，有助于评估肺腺癌患者的预后、生物学特征和合适的治疗方法。
