Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, Guangdong Province, China.
The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, Guangdong Province, China.
J Cancer Res Clin Oncol. 2024 Feb 24;150(2):103. doi: 10.1007/s00432-023-05552-x.
At present, dysfunctional CD8 T-cells in the nasopharyngeal carcinoma (NPC) tumor immune microenvironment (TIME) have caused unsatisfactory immunotherapeutic effects, such as a low response rate of anti-PD-L1 therapy. Therefore, there is an urgent need to identify reliable markers capable of accurately predicting immunotherapy efficacy.
Utilizing various algorithms for immune-infiltration evaluation, we explored the role of EIF3C in the TIME. We next found the influence of EIF3C expression on NPC based on functional analyses and RNA sequencing. By performing correlation and univariate Cox analyses of CD8 Tcell markers from scRNA-seq data, we identified four signatures, which were then used in conjunction with the lasso algorithm to determine corresponding coefficients in the resulting EIF3C-related CD8 T-cell signature (ETS). We subsequently evaluated the prognostic value of ETS using univariate and multivariate Cox regression analyses, Kaplan-Meier curves, and the area under the receiver operating characteristic curve (AUROC).
Our results demonstrate a significant relationship between low expression of EIF3C and high levels of CD8 T-cell infiltration in the TIME, as well as a correlation between EIF3C expression and progression of NPC. Based on the expression levels of four EIF3C-related CD8 T-cell marker genes, we constructed the ETS predictive model for NPC prognosis, which demonstrated success in validation. Notably, our model can also serve as an accurate indicator for detecting immunotherapy response.
Our findings suggest that EIF3C plays a significant role in NPC progression and immune modulation, particularly in CD8 T-cell infiltration. Furthermore, the ETS model holds promise as both a prognostic predictor for NPC patients and a tool for adjusting individualized immunotherapy strategies.
目前，鼻咽癌（NPC）肿瘤免疫微环境（TIME）中功能失调的 CD8 T 细胞导致免疫治疗效果不理想，如抗 PD-L1 治疗的反应率低。因此，迫切需要识别能够准确预测免疫治疗效果的可靠标志物。
利用免疫浸润评估的各种算法，我们研究了 EIF3C 在 TIME 中的作用。我们接下来通过功能分析和 RNA 测序发现了 EIF3C 表达对 NPC 的影响。通过对单细胞 RNA-seq 数据中 CD8 T 细胞标志物进行相关性和单变量 Cox 分析，我们确定了四个特征，然后结合lasso 算法确定相应的系数在由此产生的与 EIF3C 相关的 CD8 T 细胞特征（ETS）中。我们随后使用单变量和多变量 Cox 回归分析、Kaplan-Meier 曲线和接收器操作特征曲线（AUROC）下的面积来评估 ETS 的预后价值。
我们的结果表明，EIF3C 低表达与 TIME 中 CD8 T 细胞浸润水平高之间存在显著关系，EIF3C 表达与 NPC 进展之间存在相关性。基于四个与 EIF3C 相关的 CD8 T 细胞标记基因的表达水平，我们构建了 NPC 预后的 ETS 预测模型，该模型在验证中取得了成功。值得注意的是，我们的模型还可以作为检测免疫治疗反应的准确指标。
我们的研究结果表明，EIF3C 在 NPC 进展和免疫调节中起着重要作用，特别是在 CD8 T 细胞浸润方面。此外，ETS 模型有望成为 NPC 患者的预后预测指标和调整个体化免疫治疗策略的工具。
