POPDC3 is a potential biomarker for prognosis and radioresistance in patients with head and neck squamous cell carcinoma

Abstract

Radiotherapy is the primary means of treatment for patients with head and neck squamous cell carcinoma (HNSCC); however, radioresistance-induced recurrence is the primary cause of HNSCC treatment failure. Therefore, identifying specific predictive biomarkers of the response to radiotherapy may improve prognosis. In the present study, to identify the potential candidate genes associated with radioresistance in patients with HNSCC, the microarray datasets GSE9716, GSE61772 and GSE20549 were downloaded from the Gene Expression Omnibus database. The original CEL files were preprocessed using the Affymetrix package and quantile normalization and background correction were conducted using the Core package in Bioconductor. The GSE9716 dataset, consisting of 18 irradiated and 16 non-irradiated samples, was divided into two groups according to their exposure to irradiation: i) Non-irradiation group, which included 8 radioresistant samples and 8 radiosensitive samples; and ii) post-irradiation group, which included 9 radioresistant samples and 9 radiosensitive samples. The two groups were treated as separate datasets and screened. A total of 86 differentially expressed genes (DEGs) were identified in the non-irradiation group and 405 DEGs in the post-irradiation group. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis detected several significant functions associated with the DEGs. In the co-expression analysis, 76 hub genes in the light green module and 917 hub genes with a high connectivity were selected for further analysis. Finally, overlapping the DEGs and hub genes from the two groups yielded a map of 13 shared differentially expressed genes. The 13 genes showed significantly different expression in radioresistant samples compared with the radiosensitive samples before and after irradiation. Out of these genes, popeye domain-containing protein 3 (POPDC3) was highly expressed in the post-irradiation group compared with the non-irradiation group. In survival analysis, high POPDC3 expression correlated with poor a prognosis for patients with HNSCC. The independent prognostic factors were identified using univariate and multivariate Cox analyses based on The Cancer Genome Atlas database. These were incorporated into a nomogram to predict 3- and 5-year overall survival. Receiver operating characteristic curves were used to estimate the accuracy of the nomogram. Together these studies suggest that POPDC3 may serve as a potential predictive biomarker for prognosis and radioresistance of patients with HNSCC as well as clinical diagnosis and treatment of patients.

The role of Popeye domain‐containing protein 1 (POPDC1) in the progression of the malignant phenotype

“…Subsequent rapid expansion of the ISC population was also observed, leading to the conclusion that POPDC1 down-regulation and ensuing stem cell proliferation, in response to radiation therapy may be an underlying cause of resistance to radiotherapy treatment. The same phenomenon has also been observed as a result of POPDC3 down-regulation in other cancers such as HNSCC, lung cancer, and oesophageal cancer (Table 1) (He et al, 2019).…”

“…The extent of POPDC1 glycosylation in cancer cells and the functional relevance of this has yet to be investigated. This extracellular sequence is followed by three transmembrane domains and a larger, intracellular carboxy-terminal domain (CTD) Kim et al, 2010;Luo et al, 2012 Oesophageal and lung cancer -Overexpression of POPDC3 correlates with greater radiotherapy resistance He et al, 2019 Note: Expression of POPDC2 and POPDC3 varies between tissue type and across various cancer types. Dysregulation of POPDC2 is mainly observed in cardiovascular disease and breast cancer.…”

A Novel Glycolysis-related Gene Signature for Survival Prediction in Patients with Head and Neck Squamous Cell Carcinoma

“…High expression was related to tumor category, lymphatic metastasis and pathological stage. Xu He et al [21] downloaded the GSE9716, GSE61772 and GSE20549 from the Gene Expression Omnibus (GEO) database and reported that high POPDC3 expression associated with poor a prognosis for patients with HNSCC. But these genes cannot accurately predict patient survival because a single gene is modulated by many factors.…”

Risk prediction in cutaneous melanoma patients from their clinico-pathological features: superiority of clinical data over gene expression data

“…Table 1 presents a summary of clinicopathological features in the final TCGA-SKCM cohort. Further, the final dataset was normalized by quantile normalization method, which has been extensively used in the past for similar studies [34,35,36].…”