Development and Validation of an Immune-Related Signature for the Prediction of Recurrence Risk of Patients With Laryngeal Cancer

Abstract

ObjectiveOur purpose was to develop and verify an immune-related signature for predicting recurrence risk of patients with laryngeal cancer.MethodsRNA-seq data of 51 recurrence and 81 non-recurrence laryngeal cancer samples were downloaded from TCGA database, as the training set. Microarray data of 34 recurrence and 75 non-recurrence cancer samples were obtained from GEO dataset, as the validation set. Single factor cox regression was utilized to screen prognosis-related immune genes. After LASSO regression analysis, an immune-related signature was constructed. Recurrence free survival (RFS) between high- and low- recurrence risk patients was presented, followed by ROC. We also evaluated the correlation between immune infiltration and the signature using the CIBERSORT algorithm. The genes in the signature were validated in laryngeal cancer tissues by western blot or RT-qPCR. After RCN1 knockdown, migration and invasion of laryngeal cancer cells were investigated.ResultsTotally, 43 prognosis-related immune genes were identified for laryngeal cancer. Among them, eight genes were used for constructing a prognostic signature. High risk group exhibited a higher recurrence risk than low risk group. The AUC for 1-year was separately 0.803 and 0.715 in the training and verification sets, suggesting its well efficacy for predicting the recurrence. Furthermore, this signature was closely related to distinct immune cell infiltration. RCN1, DNAJA2, LASP1 and IBSP were up-regulated in laryngeal cancer. RCN1 knockdown restrained migrated and invasive abilities of laryngeal cancer cells.ConclusionOur findings identify a reliable immune-related signature that can predict the recurrence risk of patients with laryngeal cancer.

Transcriptional subtypes of glottic cancer characterized by differential activation of canonical oncogenic programming

“…This empirical data, however, has not been, or has not been able to be, leveraged to affect clinical outcomes—a recent Surveillance, Epidemiology, and End Results (SEER) analysis, for example, stipulated a 25% relative increase in case‐fatality rate between 1986 and 2016, based on a larynx cancer dataset wherein the majority of tumors were of glottic origin 12 . Though a few published efforts to systematically sequence the laryngeal cancer genome have led to the identification of discrete genetic perturbations, 13–15 the complex interplay between the wide spectrum of tumor molecular features and both patient‐centric and disease‐centric clinical characteristics necessitates a deeper, coherent approach to understand the functional consequences of these genetic alterations to guide improvements in GSCC treatment and prognostication. Moreover, investigations into prognostic molecular changes among laryngeal cancers that group all subsites together neglect the potentially disparate clinical implications and heterogenous downstream effects of these genetic perturbations; in fact, studies have identified significant molecular differences among tumors originating from the different laryngeal subsites 13 …”

Downregulation of RCN1 promotes pyroptosis in acute myeloid leukemia cells

“…RCN1 has been demonstrated to be highly expressed in a variety of tumor cells and is correlated with patient prognosis in renal cell carcinoma, prostate cancer, glioblastoma, non-small cell lung cancer, oral squamous cell carcinoma, nasopharyngeal cancer, colon cancer, laryngeal cancer, highly aggressive breast cancer, sorafenib-resistant hepatocellular carcinoma cells, and gemcitabine-insensitive human pancreatic adenocarcinoma cells, among others [20][21][22]24,25,27,[55][56][57][58][59][60][61][62][63]. Yoshida et al [64] reported that RCN1 was expressed in lymphatic endothelial cells (T-LECs) and lung cancer cells in lung tumors, but not in lymphatic endothelial cells (N-LECs) in nontumor tissues.…”