Tetraspanin gene expression levels as potential biomarkers for malignancy of gingival squamous cell carcinoma

4566 Background: Chemoradiotherapy (CRT) is a potential alternative to surgery in patients with squamous cell carcinoma of the esophagus. Complete response (CR) to CRT is essential for a good prognosis and there is a need for a predictive method of CR in CRT. Methods: The pretreatment formalin-fixed, paraffin-embedded endoscopic tumor biopsy material was obtained from 41 patients treated with a definitive concurrent CRT (5-FU/CDDP and 60 Gy) for esophageal cancer (cStage II or III). cDNA was derived from tumor cells of biopsy specimens by the laser capture microdissection and analyzed to determine mRNA expression relative to an internal reference gene (β-actin) using fluorescence-based, real-time reverse transcription PCR. Gene expression levels of thymidylate synthase, thymidine phosphorylase, dihydropyrimidine dehydrogenase, orotate phosphoribosyl transferase (OPRT), metylenetetrahydrofolate reductase, dihydrofolate reductase (DHFR), excision repair cross-complementing gene 1, vascular endothelial growth factor, epidermal growth factor receptor and matrix metalloproteinase 9 (MMP-9) were measured. Results: Median gene expression levels of OPRT and DHFR were significantly higher in CR patients (p=0.0206 and 0.0191, respectively). MMP-9 was significantly lower in CR patients (p=0.0436). When the median values of the gene expression levels were selected as the cutoff values, CR rate was significantly higher in the high OPRT group and high DHFR group (p=0.0104 and 0.0104, respectively). However, there was no statistical difference in CR rate between the low MMP-9 group and the high MMP-9 group. Multivariate analysis, including clinical stage and biomarkers, revealed that high OPRT gene expression was an independent predictive factor of CR (p=0.0329, relative risk=6.65, 95% confidence interval, 1.17–37.89%). Conclusions: The measurement of OPRT gene expression in tumor biopsies may be a predictive factor of CR to CRT in patients with squamous cell carcinoma of the esophagus. No significant financial relationships to disclose.

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Diagnostic value of integrin α3, β4, and β5 gene expression levels for the clinical outcome of tongue squamous cell carcinoma

Cancer ◽

10.1002/cncr.23295 ◽

2008 ◽

Vol 112 (6) ◽

pp. 1272-1281 ◽

Cited By ~ 39

Author(s):

Akira Kurokawa ◽

Masaki Nagata ◽

Nobutaka Kitamura ◽

Arhab A. Noman ◽

Makoto Ohnishi ◽

...

Keyword(s):

Gene Expression ◽

Squamous Cell Carcinoma ◽

Clinical Outcome ◽

Cell Carcinoma ◽

Squamous Cell ◽

Diagnostic Value ◽

Tongue Squamous Cell Carcinoma ◽

Expression Levels ◽

Gene Expression Levels

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PD-1H Expression Associated With CD68 Macrophage Marker Confers an Immune-Activated Microenvironment and Favorable Overall Survival in Human Esophageal Squamous Cell Carcinoma

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.777370 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yuangui Chen ◽

Rui Feng ◽

Bailin He ◽

Jun Wang ◽

Na Xian ◽

...

Keyword(s):

Gene Expression ◽

Overall Survival ◽

Squamous Cell Carcinoma ◽

T Cells ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Expression Levels ◽

Tumor Tissues ◽

Gene Expression Levels

Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal carcinoma (EC) in China. Although the PD-1 inhibitor pembrolizumab has been approved to treat patients with EC, its therapeutic efficacy is limited. Thus, additional immunotherapeutic targets for EC treatment are needed. Programmed Death-1 Homolog (PD-1H) is a negative checkpoint regulator that inhibits antitumor immune responses. Here, PD-1H expression in 114 patients with ESCC was evaluated by immunohistochemistry. Next, 12 randomly selected tumor tissue sections were used to assess the colocalization of PD-1H protein and multiple immune markers by multiplex immunohistochemistry. Our results demonstrated that PD-1H was expressed at high frequency in ESCC tumor tissues (85.1%). PD-1H protein was predominantly expressed in CD68+ tumor-associated macrophages and expressed at low levels in CD4+ T cells and CD8+ T cells in ESCC tumor tissues. Furthermore, based on ESCC data in The Cancer Genome Atlas (TCGA), the gene expression levels of PD-1H were positively associated with the infiltration levels of immune-activated cells especially CD8+ cytotoxic T cells. In contrast, the gene expression levels of PD-1H were negatively correlated with myeloid-derived suppressor cells (MDSCs). Importantly, PD-1H expression in tumor sites was significantly correlated with favorable overall survival in patients with ESCC. Collectively, our findings first provided direct information on the PD-1H expression pattern and distribution in ESCC, and positive correlation of PD-1H expression with overall survival suggested PD-1H expression levels could be a significant prognostic indicator for patients with ESCC. Future studies need to explore the immunoregulatory of PD-1H in the tumor microenvironment of ESCC.

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Clinical Significance and the Role of Guanylate-Binding Protein 5 in Oral Squamous Cell Carcinoma

Cancers ◽

10.3390/cancers13164043 ◽

2021 ◽

Vol 13 (16) ◽

pp. 4043

Author(s):

Pei-Feng Liu ◽

Chih-Wen Shu ◽

Cheng-Hsin Lee ◽

Huei-Cin Sie ◽

Huei-Han Liou ◽

...

Keyword(s):

Gene Expression ◽

Squamous Cell Carcinoma ◽

Cell Differentiation ◽

Oral Cancer ◽

Cell Carcinoma ◽

Cancer Patients ◽

Squamous Cell ◽

Expression Levels ◽

Oral Cancer Patients ◽

Gene Expression Levels

Guanylate binding protein 5 (GBP5) is the interferon (IFN)-inducible subfamily of guanosine triphosphatases (GTPases) and is involved in pathogen defense. However, the role played by GBP5 in cancer development, especially in oral squamous cell carcinoma (OSCC), is still unknown. Herein, next-generation sequencing analysis showed that the gene expression levels of GBP5 were significantly higher in OSCC tissues compared with those found in corresponding tumor adjacent normal tissues (CTAN) from two pairs of OSCC patients. Higher gene expression levels of GBP5 were also found in tumor tissues of 23 buccal mucosal squamous cell carcinoma (BMSCC)/14 tongue squamous cell carcinoma (TSCC) patients and 30 oral cancer patients from The Cancer Genome Atlas (TCGA) database compared with those in CTAN tissues. Immunohistochemical results showed that protein expression levels of GBP5 were also higher in the tumor tissues of 353 OSCC patients including 117 BMSCC, 187 TSCC, and 49 lip squamous cell carcinoma patients. Moreover, TCGA database analysis indicated that high gene expression levels of GBP5 were associated with poor overall survival in oral cancer patients with moderate/poor cell differentiation, and associated with poor disease-free survival in oral cancer patients with moderate/poor cell differentiation and lymph node metastasis. Furthermore, GBP5-knockdowned cells exhibited decreased cell growth, arrest at G1 phase, and decreased invasion/migration. The gene expression of markers for epithelial−mesenchymal transition and cancer stemness was also reduced in GBP5-silenced oral cancer cells. Taken together, GBP5 might be a potential biomarker and therapeutic target for OSCC patients, especially for those with poor cell differentiation and lymph node metastasis.

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Pparg may Promote Chemosensitivity of Hypopharyngeal Squamous Cell Carcinoma

PPAR Research ◽

10.1155/2020/6452182 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Meng Lian ◽

Jiaming Chen ◽

Xixi Shen ◽

Lizhen Hou ◽

Jugao Fang

Keyword(s):

Gene Expression ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Large Scale ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Regulatory Pathways ◽

Hypopharyngeal Squamous Cell Carcinoma ◽

Expression Levels

The upregulation of peroxisome proliferator-activated receptor gamma (PPARG) has been shown to increase the chemosensitivity of several human cancers. This study is aimed at studying if PPARG sensitizes hypopharyngeal squamous cell carcinoma (HSCC) in chemotherapeutic treatments and at dissecting possible mechanisms of observed effects. We integrated large-scale literature data and HSCC gene expression data to identify regulatory pathways that link PPARG and chemosensitivity in HSCC. Expression levels of molecules within the PPARG regulatory pathways were compared in 21 patients that underwent chemotherapy for primary HSCC, including 12 chemotherapy-sensitive patients (CSP) and 9 chemotherapy-nonsensitive patients (CNSP). In the CPS group, expression levels of PPARG were higher than that in the CNSP group (log‐fold‐change=0.50). Structured text mining identified two chemosensitivity-related regulatory pathways driven by PPARG. In the CSP group, expression levels for 7 chemosensitivity-promoting genes were increased, while for 13 chemosensitivity suppressing the gene expression levels were decreased. Our results support the chemosensitivity-promoting role of PPARG in HSCC tumor cells, most likely by affecting both cell proliferation and cell motility pathways.

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Ferroptosis Driver SOCS1 and Suppressor FTH1 Independently Correlate With M1 and M2 Macrophage Infiltration in Head and Neck Squamous Cell Carcinoma

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.727762 ◽

2021 ◽

Vol 9 ◽

Author(s):

Zhang-Wei Hu ◽

Yi-Hui Wen ◽

Ren-Qiang Ma ◽

Lin Chen ◽

Xue-Lan Zeng ◽

...

Keyword(s):

Gene Expression ◽

Squamous Cell Carcinoma ◽

Prognostic Factors ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma ◽

Macrophage Infiltration ◽

M2 Macrophage ◽

Expression Levels

ObjectiveTo investigate the role of ferroptosis, an iron-dependent form of non-apoptotic cell death, in the head and neck squamous cell carcinoma (HNSCC) immune microenvironment.Materials and MethodsA list of ferroptosis-related genes was obtained from the FerrDb database. Gene expression data were acquired from the cancer genome atlas (TCGA) and analyzed using the R language. Protein–protein interaction analysis was conducted using STRING and GeneMANIA. The correlations between gene expression levels and a patient’s survival were analyzed using GEPIA, the Kaplan–Meier estimate, and a multivariate Cox proportional hazards model. The expression results were verified using Oncomine and Human Protein Atlas data. We used the TIMER, GEPIA2, GEPIA2021, and TIMER2 databases to investigate the relationships between gene expression and infiltrating immune cells.ResultsAnalysis of differentially expressed genes (DEGs) identified nine each ferroptosis drivers and ferroptosis suppressors, among which four genes correlated with survival as follows: two drivers (SOCS1, CDKN2A) associated with better survival and two suppressors (FTH1, CAV1) associated with poorer survival. Multivariate Cox survival analysis identified SOCS1 and FTH1 as independent prognostic factors for HNSCC, and their higher expression levels were verified using Oncomine and HPA data. The results acquired using TIMER, GEPIA2, GEPIA2021, and TIMER2 data revealed that the driver SOCS1 and the suppressor FTH1 independently correlated with M1 and M2 macrophage infiltration.ConclusionsThe ferroptosis driver SOCS1 and suppressor FTH1 are independent prognostic factors and that correlate with M1 and M2 macrophage infiltration in HNSCC. Targeting ferroptosis-immunomodulation may serve as a strategy to enhance the activity of immunotherapy.

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Bioinformatics-based discovery of PYGM and TNNC2 as potential biomarkers of head and neck squamous cell carcinoma

Bioscience Reports ◽

10.1042/bsr20191612 ◽

2019 ◽

Vol 39 (7) ◽

Cited By ~ 1

Author(s):

Yu Jin ◽

Ya Yang

Keyword(s):

Gene Expression ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Molecular Mechanisms ◽

Neck Squamous Cell Carcinoma ◽

High Morbidity ◽

Aberrant Expression ◽

Potential Biomarkers

Abstract Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with high morbidity and mortality rates and ranks as the sixth most common cancer all over the world. Despite numerous advancements in therapeutic methods, the prognosis of HNSCC patients still remains poor. Therefore, there is an urgent need to have a better understanding of the molecular mechanisms underlying HNSCC progression and to identify essential genes that could serve as effective biomarkers and potential treatment targets. In the present study, original data of three independent datasets were downloaded from the Gene Expression Omnibus database (GEO) and R language was applied to screen out the differentially expressed genes (DEGs). PYGM and TNNC2 were finally selected from the overlapping DEGs of three datasets for further analyses. Transcriptional and survival data related to PYGM and TNNC2 was detected through multiple online databases such as Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), cBioportal, and UALCAN. Quantitative real-time polymerase chain reaction (qPCR) analysis was adopted for the validation of PYGM and TNNC2 mRNA level in HNSCC tissues and cell lines. Survival curves were plotted to evaluate the association of these two genes with HNSCC prognosis. It was demonstrated that PYGM and TNNC2 were significantly down-regulated in HNSCC and the aberrant expression of PYGM and TNNC2 were correlated with HNSCC prognosis, implying the potential of exploiting them as therapeutic targets for HNSCC treatment or potential biomarkers for diagnosis and prognosis.

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