Dataset Information

Identification of a Cancer Stem Cells Signature of Head and Neck Squamous Cell Carcinoma.

ABSTRACT: Background: Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most widespread and deadly cancer. In recent times, it has been determined that undifferentiated cell populations with stem cell-like properties in HNSCC are major factors influencing recurrence and progression. Method: In this study, we determine key genes related to stemness by merging WGCNA with HNSCC mRNAsi based on the online database. Results: We first download the mRNA expression-based stemness index (mRNAsi) data and contrast the expression levels of mRNAsi in cancers and control samples; we found significantly elevated mRNAsi expressions in HNSCC tissues (p = 0.002). Moreover, the brown module showed a relatively high negative correlation with mRNAsi (cor = -0.8). Thus, we selected the brown module as the interesting module and used it for following analysis. We screened 20 key genes (PDGFRB, PLPP4, CALU, ADAMTS14, COL5A3, KCNE4, LOXL1, CLEC11A, PODN,BGN, AEBP1, COL1A2, LAMA4, LOXL2, LRRC15, THY1, SPON2, COL1A1, NID2, and AC134312.5) including and as to decide the neighbor genes biological interaction network of these 20 stemness-related genes in HNSCC. The top 10 frequent alterations were PIK3CA, FGF3, FGF19, FGF4, DVL3, P3H2, GNB4, COL22A1, COL14A1, and PLOD2. Conclusion: This study showed the critical role of stemness-related genes in HNSCC. However, more related studies are needed to confirm these results.

SUBMITTER: Wu ZH

PROVIDER: S-EPMC9132479 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Identification of a Cancer Stem Cells Signature of Head and Neck Squamous Cell Carcinoma.

Wu Zeng-Hong ZH Li Cheng C Zhang You-Jing YJ Zhou Wen W

Frontiers in genetics 20220511

Background: Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most widespread and deadly cancer. In recent times, it has been determined that undifferentiated cell populations with stem cell-like properties in HNSCC are major factors influencing recurrence and progression. Method: In this study, we determine key genes related to stemness by merging WGCNA with HNSCC mRNAsi based on the online database. Results: We first download the mRNA expression-based stemne ...[more]

PMID: 35646104

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Project description:Cancer stem cell (CSC) subpopulations within moderately differentiated head and neck cutaneous squamous cell carcinoma (MDHNcSCC) express the components of the renin-angiotensin system (RAS). This study investigated the expression of cathepsins B, D, and G, which constitute bypass loops of the RAS, by CSCs in MDHNcSCC.MethodsImmunohistochemical staining was performed on MDHNcSCC tissue samples from 15 patients to determine the expression of cathepsins B, D, and G. Co-localization of these cathepsins with the embryonic stem cell markers Octamer-binding transcription factor 4 (OCT4) and c-MYC was investigated with immunofluorescence staining. Reverse transcription quantitative polymerase chain reaction was performed on 5 MDHNcSCC tissue samples to investigate transcript expression of cathepsins B, D and G. Western blotting and enzymatic activity assays were performed on 5 MDHNcSCC tissue samples and 6 MDHNcSCC-derived primary cell lines to confirm protein expression, transcript expression, and functional activity of these cathepsins, respectively.ResultsImmunohistochemical staining demonstrated the expression of cathepsins B, D, and G in all MDHNcSCC tissue samples. Immunofluorescence staining showed localization of cathepsins B and D to the c-MYC+ CSC subpopulations and the OCT4+ CSC subpopulations within the tumor nests and the peritumoral stroma. Cathepsin G was expressed on the tryptase+/c-MYC+ cells within the peritumoral stroma. Reverse transcription quantitative polymerase chain reaction demonstrated transcript expression of cathepsins B, D and G in the MDHNcSCC tissue samples. Western blotting and enzymatic activity assays confirmed protein expression and functional activity of cathepsins B and D in the MDHNcSCC tissue samples and MDHNcSCC-derived primary cell lines, respectively.ConclusionsCathepsins B, D, and G are expressed in MDHNcSCC with functionally active cathepsins B and D localizing to the CSC subpopulations, and cathepsin G is expressed by mast cells, suggesting the potential use of cathepsin inhibitors in addition to RAS blockade to target CSCs in MDHNcSCC.

Project description:BackgroundHead and neck squamous cell carcinoma (HNSCC) is a life-threatening disease with poor prognosis. Pyroptosis has been recently disclosed as a programmed cell death triggered by invasive infection, involved in cancer development. However, the prognosis role of pyroptosis-related genes in HNSCC has not been discussed.MethodsThe RNA sequence data of pyroptosis-related genes were obtained from The Cancer Genome Atlas (TCGA) database. Cox regression and the least absolute shrinkage and selection operator (LASSO) analysis were performed to screen the HNSCC survival-related signature genes. We established a HNSCC risk model with the identified prognostic genes, then divided the HNSCC patients into low- and high-risk subgroups according to median risk score. Moreover, we utilized Gene Expression Omnibus (GEO) dataset to validate the risk model. Go and KEGG analyses were conducted to reveal the potential function of differential expression of genes that identified between low- and high-risk subgroups. ESTIMATE algorithm was performed to investigate the immune infiltration of tumors. Correlation between signature gene expression and drug-sensitivity was disclosed by Spearman's analysis.ResultsWe constructed a HNSCC risk model with identified seven pyroptosis-related genes (CASP1, GSDME, IL6, NLRP1, NLRP2, NLRP6, and NOD2) as prognostic signature genes. High-risk subgroup of HNSCC patients in TCGA cohort correlated with lower survival probability than patients from low-risk subgroup (p < .001), and the result is verified with GEO dataset. In addition, 161 genes were identified differentially expressed between the low- and high-risk subgroups in the TCGA cohort, mainly related to immune response. Higher PD-L1 expression level was found in the high-risk subgroup that indicated the possible employment of immune checkpoint inhibitors. IL6 was positively correlated with WZ3105 and MPS-1-IN-1 in the cancer therapeutics response portal database.ConclusionWe built and verified a risk model for HNSCC prognosis using seven pyroptosis-related signature genes, which could predict the overall survival of HNSCC patients and facilitate treatment.

Project description:BackgroundHead and neck squamous cell carcinoma (HNSCC) are the most common cancers in the head and neck. Therapeutic response-related genes (TRRGs) are closely associated with carcinogenesis and prognosis in HNSCC. However, the clinical value and prognostic significance of TRRGs are still unclear. We aimed to construct a prognostic risk model to predict therapy response and prognosis in TRRGs-defined subgroups of HNSCC.MethodsThe multiomics data and clinical information of HNSCC patients were downloaded from The Cancer Genome Atlas (TCGA). The profile data GSE65858 and GSE67614 chip was downloaded from public functional genomics data Gene Expression Omnibus (GEO). Based on TCGA-HNSC database, patients were divided into a remission group and a non-remission group according to therapy response, and differentially expressed TRRGs between those two groups were screened. Using Cox regression analysis and Least absolute shrinkage and selection operator (LASSO) analysis, candidate TRRGs that can predict the prognosis of HNSCC were identified and used to construct a TRRGs-based signature and a prognostic nomogram.ResultA total of 1896 differentially expressed TRRGs were screened, including 1530 upregulated genes and 366 downregulated genes. Then, 206 differently expressed TRRGs that was significantly associated with the survival were chosen using univariate Cox regression analysis. Finally, a total of 20 candidate TRRGs genes were identified by LASSO analysis to establish a signature for risk prediction, and the risk score of each patient was calculated. Patients were divided into a high-risk group (Risk-H) and a low-risk group (Risk-L) based on the risk score. Results showed that the Risk-L patients had better overall survival (OS) than Risk-H patients. Receiver operating characteristic (ROC) curve analysis revealed great predictive performance for 1-, 3-, and 5-year OS in TCGA-HNSC and GEO databases. Moreover, for patients treated with post-operative radiotherapy, Risk-L patients had longer OS and lower recurrence than Risk-H patients. The nomogram involves risk score and other clinical factors had good performance in predicting survival probability.ConclusionsThe proposed risk prognostic signature and Nomogram based on TRRGs are novel promising tools for predicting therapy response and overall survival in HNSCC patients.

Dataset Information

Identification of a Cancer Stem Cells Signature of Head and Neck Squamous Cell Carcinoma.

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Identification of a Cancer Stem Cells Signature of Head and Neck Squamous Cell Carcinoma.

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