Department of Otorhinolaryngology Head and Neck Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, China.
Department of Otorhinolaryngology Head and Neck Surgery, Lihuili Hospital affiliated to Ningbo University, Ningbo, China.
Cancer Med. 2022 Dec;11(24):5097-5112. doi: 10.1002/cam4.4819. Epub 2022 May 14.
Pyroptosis plays an essential function in carcinogenesis and the antitumor immune response. Herein, we constructed a pyroptosis-related long noncoding RNA (prLncRNA) signature to predict therapeutic effects and outcomes for head and neck squamous cell carcinoma (HNSCC) patients.
Patients obtained from the TCGA-HNSC project were divided randomly into the training as well as the validation sets at a ratio of 7:3. A novel prognostic prLncRNA signature was constructed from the results of the training set using the least absolute shrinkage and selection operation. The medium value was used as the basis for categorizing all HNSCC patients into a low- or high-risk cohort. Cox regression and Kaplan-Meier (KM) survival analyses were executed to estimate the prognostic value. We also evaluated the functional enrichment, tumor microenvironment, immune cell infiltration, and the sensitivity to chemotherapy and immunotherapy between the high- and low-risk cohorts.
Nineteen prognostic prlncRNAs were identified to establish the prognostic signature. Multivariate Cox regression and KM survival analyses confirmed that this prlncRNA signature might serve as an independent prognostic indicator of patient survival, which was subsequently confirmed using a validating dataset. Multiple ROC curves indicated the prlncRNA signature presented a more predictive power than clinicopathological factors (age, sex, tumor grade, and tumor stage). GO, KEGG, and GSEA enrichment analysis disclosed several immune-related pathways which appeared to be enhanced in the low-risk cohort. ESTIMATE, CIBERSORT, and ssGSEA algorithms indicated considerable differences in the tumor microenvironment and immune cell infiltration in the low- and high-risk cohorts. Furthermore, the low-risk cohort was predicted to achieve a better response to immunotherapeutic drugs, while in contrast, the high-risk cohort would be more sensitive to chemotherapy drugs.
Our findings robustly demonstrate that our constructed prlncRNA signature could serve as an efficient indicator of prognosis, immunotherapy response, and chemosensitivity for HNSCC patients.
细胞焦亡在癌症发生和抗肿瘤免疫反应中起着重要作用。在此，我们构建了一个与细胞焦亡相关的长链非编码 RNA（prLncRNA）特征，以预测头颈部鳞状细胞癌（HNSCC）患者的治疗效果和结局。
从 TCGA-HNSC 项目中获得的患者以 7:3 的比例随机分为训练集和验证集。使用最小绝对收缩和选择算子（LASSO）从训练集结果中构建新的预后 prLncRNA 特征。中位数被用作将所有 HNSCC 患者分为低风险或高风险队列的依据。进行 Cox 回归和 Kaplan-Meier（KM）生存分析以估计预后价值。我们还评估了高低风险队列之间的功能富集、肿瘤微环境、免疫细胞浸润以及对化疗和免疫治疗的敏感性。
确定了 19 个预后 prlncRNA 来建立预后特征。多变量 Cox 回归和 KM 生存分析证实，该 prlncRNA 特征可以作为患者生存的独立预后指标，随后在验证数据集中得到验证。多个 ROC 曲线表明，prlncRNA 特征比临床病理因素（年龄、性别、肿瘤分级和肿瘤分期）具有更高的预测能力。GO、KEGG 和 GSEA 富集分析揭示了几个免疫相关途径在低风险队列中似乎增强。ESTIMATE、CIBERSORT 和 ssGSEA 算法表明，低风险和高风险队列之间的肿瘤微环境和免疫细胞浸润存在显著差异。此外，低风险队列被预测对免疫治疗药物有更好的反应，而相反，高风险队列对化疗药物更敏感。
我们的研究结果有力地证明，我们构建的 prlncRNA 特征可以作为 HNSCC 患者预后、免疫治疗反应和化疗敏感性的有效指标。
