Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Department of Thoracic Surgery, Third Affiliated Hospital of Naval Medical University, Shanghai 201805, China.
Aging (Albany NY). 2023 Oct 6;15(19):10473-10500. doi: 10.18632/aging.205089.
Precisely forecasting the prognosis of esophageal squamous cell carcinoma (ESCC) patients is a formidable challenge. Cuproptosis has been implicated in ESCC pathogenesis; however, the prognostic value of cuproptosis-associated long noncoding RNAs (CuRLs) in ESCC is unclear.
Transcriptomic and clinical data related to ESCC were sourced from The Cancer Genome Atlas (TCGA). Using coexpression and Cox regression analysis to identify prognostically significant CuRLs, a prognostic signature was created. Nomogram models were established by incorporating the risk score and clinical characteristics. Tumor Immune Dysfunction and Rejection (TIDE) scores were derived by conducting an immune landscape analysis and evaluating the tumor mutational burden (TMB). Drug sensitivity analysis was performed to explore the underlying molecular mechanisms and guide clinical dosing.
Our risk score based on 5 CuRLs accurately predicted poorer prognosis in high-risk ESCC patients across almost all subgroups. The nomogram that included the risk score provided more precise prognostic predictions. Immune pathways, such as the B-cell receptor signaling pathway, were enriched in the datasets from high-risk patients. High TMB in high-risk patients indicated a relatively poor prognosis. High-risk patients with lower TIDE scores were found to benefit more from immunotherapy. High-risk patients exhibited greater responsiveness to Nilotinib, BI-2536, P22077, Zoledronate, and Fulvestrant, as revealed by drug sensitivity analysis. Real-time PCR validation demonstrated significant differential expression of four CuRLs between ESCC and normal cell lines.
The above risk score and nomogram can accurately predict prognosis in ESCC patients and provide guidance for chemotherapy and immunotherapy.
准确预测食管鳞状细胞癌（ESCC）患者的预后是一项艰巨的挑战。铜死亡与 ESCC 的发病机制有关；然而，铜死亡相关长链非编码 RNA（CuRLs）在 ESCC 中的预后价值尚不清楚。
从癌症基因组图谱（TCGA）中获取与 ESCC 相关的转录组和临床数据。使用共表达和 Cox 回归分析来识别具有预后意义的 CuRLs，构建预后签名。通过纳入风险评分和临床特征，建立列线图模型。通过进行免疫景观分析并评估肿瘤突变负担（TMB），得出肿瘤免疫功能障碍和排斥（TIDE）评分。进行药物敏感性分析，以探索潜在的分子机制并指导临床给药。
我们基于 5 个 CuRLs 的风险评分能够准确预测高风险 ESCC 患者在几乎所有亚组中的预后较差。包含风险评分的列线图提供了更精确的预后预测。在高风险患者的数据集，B 细胞受体信号通路等免疫途径被富集。高风险患者的 TMB 较高，提示预后相对较差。高风险患者中 TIDE 评分较低者，从免疫治疗中获益更多。药物敏感性分析表明，高风险患者对尼罗替尼、BI-2536、P22077、唑来膦酸和氟维司群的反应性更高。实时 PCR 验证表明，ESCC 与正常细胞系之间存在 4 个 CuRLs 的显著差异表达。
上述风险评分和列线图可以准确预测 ESCC 患者的预后，并为化疗和免疫治疗提供指导。
