School of Stomatology, Wannan Medical College, Wuhu, China; Anhui Provincial Engineering Research Center for Dental Materials and Application, Wannan Medical College, Wuhu, China.
Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, Nanjing, China.
J Stomatol Oral Maxillofac Surg. 2024 Sep;125(4S):101937. doi: 10.1016/j.jormas.2024.101937. Epub 2024 Jun 4.
Accumulating evidence has suggested that RNA binding protein (RBP) dysregulation plays an essential role during tumorigenesis. Here, we sought to explore the potential biological functions and clinical significance of RBP and develop diagnostic and prognostic signatures based on RBP in patients with head and neck squamous cell carcinoma (HNSCC).
The differently expressed RBPs between HNSCC samples and their normal counterparts were identified using the Limma package. The immunohistochemistry (IHC) images of several RBPs were collected from the Human Protein Atlas database. The diagnostic signature based on RBP was built by LASSO-logistic regression and random forest. The prognostic signature based on RBP was constructed by LASSO and stepwise Cox regression analysis in the training cohort and validated in the validation cohort.
Eighty-four aberrantly expressed RBPs were obtained, comprising 41 up-regulated and 43 down-regulated RBPs. Seven RBP genes (CPEB3, PDCD4, ENDOU, PARP12, DNMT3B, IGF2BP1, EXO1) were identified as diagnostic-related hub genes. They were used to establish a diagnostic RBP signature risk score (DRBPS) model by the coefficients in least absolute shrinkage and selection operator (LASSO)-logistic regression analysis and showed high specificity and sensitivity in the training (area under the receiver operating characteristic curve (AUC) = 0.998), and in all validation cohorts (AUC > 0.95 for all). Similarly, seven RBP genes (MKRN3, ZC3H12D, EIF5A2, AFF3, SIDT1, RBM24, and NR0B1) were identified as prognosis-associated hub genes by LASSO and stepwise multiple Cox regression analyses and were used to construct the prognostic model named as PRBPS. The AUC of the time-dependent receiver operator characteristic curve of the prognostic model was 0.664 at 3 years and 0.635 at 5 years in the training cohort and 0.720, 0.777 in the validation cohort, showing a favorable predictive efficacy for prognosis in HNSCC.
Our results demonstrate the value of consideration of RBP in the diagnosis and prognosis for HNSCC and provide a novel insight into understanding the potential role of dysregulated RBP in HNSCC.
越来越多的证据表明，RNA 结合蛋白（RBP）失调在肿瘤发生过程中起着至关重要的作用。在这里，我们试图探讨 RBP 在头颈部鳞状细胞癌（HNSCC）患者中的潜在生物学功能和临床意义，并基于 RBP 开发诊断和预后特征。
使用 Limma 包鉴定 HNSCC 样本与其正常对应物之间差异表达的 RBP。从人类蛋白质图谱数据库中收集了几种 RBP 的免疫组化（IHC）图像。基于 RBP 的诊断特征通过 LASSO-logistic 回归和随机森林建立。基于 RBP 的预后特征通过训练队列中的 LASSO 和逐步 Cox 回归分析以及验证队列中的验证构建。
获得了 84 个异常表达的 RBP，包括 41 个上调和 43 个下调的 RBP。7 个 RBP 基因（CPEB3、PDCD4、ENDOU、PARP12、DNMT3B、IGF2BP1、EXO1）被鉴定为与诊断相关的枢纽基因。它们通过最小绝对值收缩和选择算子（LASSO）-logistic 回归分析中的系数被用于建立诊断 RBP 特征风险评分（DRBPS）模型，在训练组中具有高特异性和敏感性（AUC = 0.998），并且在所有验证组中（AUC>0.95 所有）。同样，通过 LASSO 和逐步多 Cox 回归分析，7 个 RBP 基因（MKRN3、ZC3H12D、EIF5A2、AFF3、SIDT1、RBM24 和 NR0B1）被鉴定为预后相关的枢纽基因，并用于构建预后模型命名为 PRBPS。该预后模型的时间依赖性接收器工作特征曲线的 AUC 在训练队列中为 3 年时为 0.664，5 年时为 0.635，在验证队列中为 0.720、0.777，显示出对 HNSCC 预后的有利预测效果。
我们的结果证明了在 HNSCC 的诊断和预后中考虑 RBP 的价值，并为理解失调的 RBP 在 HNSCC 中的潜在作用提供了新的见解。
