Dataset Information

CCTs as new biomarkers for the prognosis of head and neck squamous cancer.

ABSTRACT: The chaperonin-containing T-complex protein 1 (CCT) subunits participate in diverse diseases. However, little is known about their expression and prognostic values in human head and neck squamous cancer (HNSC). This article aims to evaluate the effects of CCT subunits regarding their prognostic values for HNSC. We mined the transcriptional and survival data of CCTs in HNSC patients from online databases. A protein-protein interaction network was constructed and a functional enrichment analysis of target genes was performed. We observed that the mRNA expression levels of CCT1/2/3/4/5/6/7/8 were higher in HNSC tissues than in normal tissues. Survival analysis revealed that the high mRNA transcriptional levels of CCT3/4/5/6/7/8 were associated with a low overall survival. The expression levels of CCT4/7 were correlated with advanced tumor stage. And the overexpression of CCT4 was associated with higher N stage of patients. Validation of CCTs' differential expression and prognostic values was achieved by the Human Protein Atlas and GEO datasets. Mechanistic exploration of CCT subunits by the functional enrichment analysis suggests that these genes may influence the HNSC prognosis by regulating PI3K-Akt and other pathways. This study implies that CCT3/4/6/7/8 are promising biomarkers for the prognosis of HNSC.

SUBMITTER: Dong Y

PROVIDER: S-EPMC7706129 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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CCTs as new biomarkers for the prognosis of head and neck squamous cancer.

Dong Yanbo Y Lu Siyu S Wang Zhenxiao Z Liu Liangfa L

Open medicine (Warsaw, Poland) 20200713 1

The chaperonin-containing T-complex protein 1 (CCT) subunits participate in diverse diseases. However, little is known about their expression and prognostic values in human head and neck squamous cancer (HNSC). This article aims to evaluate the effects of CCT subunits regarding their prognostic values for HNSC. We mined the transcriptional and survival data of CCTs in HNSC patients from online databases. A protein-protein interaction network was constructed and a functional enrichment analysis o ...[more]

PMID: 33313411

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Project description:Background: Head and neck squamous carcinoma (HNSC) is one of the most common malignant tumors with high incidence and poor prognosis. Transmembrane emp24 structural domain (TMED) proteins are involved in protein transport and vesicle budding processes, which have implicated various malignancies' progression. However, the roles of TMEDs in HNSC, especially in terms of development and prognosis, have not been fully elucidated. Methods: We applied TIMER 2.0, UALCAN, GEPIA 2, Kaplan-Meier plotter, GEO, The Human Protein Atlas (HPA), cBioPortal, Linkedomics, Metascape, GRNdb, STRING, and Cytoscape to investigate the roles of TMED family members in HNSC. Results: Compared with normal tissues, the mRNA expression levels of TMED1/2/4/5/7/8/9/10 were significantly increased in the TCGA HNSC dataset. And we combined GEPIA 2 and Kaplan-Meier Plotter to select TMED2/9/10 with prognostic value. Then we detected the levels of mRNA in the GEO HNSC database and the protein expression in HPA. It was found that the mRNA and protein expression levels of TMED2/9/10 were increased in HNSC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that TMED2/9/10 and their co-expressed genes promoted the malignant behavior of tumors by participating in biological processes such as intracellular transferase complex, protein transport, focal adhesion, intracellular protein processing. Single-cell analysis and immune infiltration analysis suggested that immune responses of cancer-associated fibroblasts and endothelial cells might be associated with prognosis. Finally, the transcription factors-genes network and protein-protein functional interaction network pointed to genes such as X-box binding protein 1 (XBP1) and TMED7, which might cooperate with TMED2/9/10 to change the progression of HNSC. Conclusions: Our study implied that TMED2/9/10 and related genes mightjointly affect the prognosis of HNSC, providing specific clues for further experimental research, personalized diagnosis strategies, and targeted clinical therapy for HNSC.

Project description:BackgroundHead and neck squamous cell carcinoma (HNSCC) is a frequently lethal malignancy, and the mortality is considerably high. The tumor microenvironment (TME) has been identified as a critical participation in cancer development, treatment, and prognosis. However, competing endogenous RNA (ceRNA) networks grouping with immune/stromal scores of HNSCC patients need to be further illustrated. Therefore, our study aimed to provide clues for searching promising prognostic markers of TME in HNSCC.Materials and methodsESTIMATE algorithm was used to calculate immune scores and stromal scores of the enrolled HNSCC patients. Differentially expressed genes (DEGs), lncRNAs (DELs), and miRNAs (DEMs) were identified by comparing the expression difference between high and low immune/stromal scores. Then, a ceRNA network and protein-protein interaction (PPI) network were constructed for selecting hub regulators. In addition, survival analysis was performed to access the association between immune scores, stromal scores, and differentially expressed RNAs in the ceRNA network and the overall survival (OS) of HNSCC patients. Then, the GSE65858 datasets from Gene Expression Omnibus (GEO) database was used for verification. At last, the difference between the clinical characteristics and immune cell infiltration in different expression groups of IL10RA, PRF1, and IL2RA was analyzed.ResultsSurvival analysis showed a better OS in the high immune score group, and then we constructed a ceRNA network composed of 97 DEGs, 79 DELs and 22 DEMs. Within the ceRNA network, FOXP3, IL10RA, STAT5A, PRF1, IL2RA, miR-148a-3p, miR-3065-3p, and lncRNAs, including CXCR2P1, HNRNPA1P21, CTA-384D8.36, and IGHV1OR15-2, were closely correlated with the OS of HNSCC patients. Especially, using the data from GSE65858, we successfully verified that IL10RA, PRF1, and IL2RA were not only significantly upregulated in patients high immune scores, but also their high expressions were associated with longer survival time. In addition, stratified analysis showed that PRF1 and IL2RA might be involved in the mechanism of tumor progress.ConclusionIn conclusion, we constructed a ceRNA network related to the TME of HNSCC, which provides candidates for therapeutic intervention and prognosis evaluation.

Project description:Background: Cuproptosis is a new type of cell death that induces protein toxic stress and eventually leads to cell death. Hence, regulating cuproptosis in tumor cells is a new therapeutic approach. However, studies on cuproptosis-related long noncoding RNA (lncRNA) in head and neck squamous cell carcinoma (HNSC) have not been found. This study aimed to explore the cuproptosis-related lncRNAs prognostic marker and their relationship to immune microenvironment in HNSC by using bioinformatics methods. Methods: RNA sequencing, genomic mutations, and clinical data of TCGA_HNSC were downloaded from The Cancer Genome Atlas. HNSC patients were randomly assigned to either a training group or a validation cohort. The least absolute shrinkage and selection operator Cox regression and multivariate Cox regression models were used to determine the prognostic model in the training cohort, and its independent prognostic effect was further confirmed in the validation and entire cohorts. Results: Based on previous literature, we collected 19 genes associated with cuproptosis. Afterward, 783 cuproptosis-related lncRNAs were obtained through coexpression. Cox model revealed and constructed eight cuproptosis-related lncRNAs prognostic marker (AL132800.1, AC090587.1, AC079160.1, AC011462.4, AL157888.1, GRHL3-AS1, SNHG16, and AC021148.2). Patients were divided into high- and low-risk groups based on the median risk score. The Kaplan–Meier survival curve revealed that the overall survival between the high- and low-risk groups was statistically significant. The receiver operating characteristic curve and principal component analysis demonstrated the accurate prognostic ability of the model. Univariate and multivariate Cox regression analysis showed that risk score was an independent prognostic factor. In addition, we used multivariate Cox regression to establish a nomogram of the predictive power of prognostic markers. The tumor mutation burden showed significant differences between the high- and low-risk groups. HNSC patients in the high-risk group responded better to immunotherapy than those in the low-risk group. We also found that risk scores were significantly associated with drug sensitivity in HNSC. Conclusion: In summary, our study identified eight cuprotosis-related lncRNAs signature of HNSC as the prognostic predictor, which may be promising biomarkers for predicting the benefit of HNSC immunotherapy as well as drug sensitivity.

Project description:Human papillomavirus (HPV) is an accepted cause of head and neck squamous cell carcinoma (HNSCC), and patients with HPV-associated HNSCC have a favorable prognosis. Currently, there is no general guidance on the most appropriate biomarkers for clinical assessment of HPV in these malignancies. We compared PCR-based and serologic HPV assays, as well as p16 immunohistochemistry, individually and in combination in a single population-based study to assess their associations with overall survival among patients with HNSCC, and thus their potential value as biomarkers. HPV16 serology was determined for 488 patients; immunohistochemical detection of p16 expression in tumors was conducted in a subset of 233 cases, and PCR-based methods to assess the presence of HPV16 DNA in a subset of 179 cases of tumors. Considering each biomarker individually in the subset of patients studied for all endpoints, seropositivity for the E6 and E7 proteins was significantly associated with enhanced all-cause survival in oropharyngeal disease [HR(E6/E7+) = 0.1, 95% confidence interval (CI) = 0.02-0.3]. Neither the presence of HPV16 DNA nor p16 immunostaining was associated with significant enhanced overall survival in oropharyngeal disease (HR(DNA) = 0.9, 95% CI = 0.3-2.9; HR(p16) = 0.3, 95% CI = 0.1-1.1). However, the combination of HPV-positive DNA and E6 or E7 serology was associated with enhanced overall survival in oropharyngeal disease (HR(DNA+/E6/E7+) = 0.1, 95% CI = 0.02-1.0), whereas E6/E7 seronegative patients with evidence of HPV in tumor DNA did not show any evidence of favorable survival (HR(DNA+/E6-/E7-) = 3.4, 95% CI = 0.6-18.1). Furthermore, patients with p16 staining and E6 or E7 seropositivity had favorable survival from oropharyngeal disease (HR(p16+/E6/E7+) = 0.1, 95% CI = 0.02-0.4), whereas patients who were p16 positive and E6/E7 seronegative had significantly increased hazard of all causes of death (HR(p16+/E6-/E7-) = 3.1, 95% CI = 1.2-7.7). A stronger association of HPV presence with prognosis (assessed by all-cause survival) is observed when "HPV-associated" HNSCC is defined using tumor status (HPV DNA status or P16) and HPV E6/E7 serology in combination rather using tumor HPV status alone.

Dataset Information

CCTs as new biomarkers for the prognosis of head and neck squamous cancer.

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CCTs as new biomarkers for the prognosis of head and neck squamous cancer.

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