SERPINH1 is a Potential Prognostic Biomarker and Correlated With Immune Infiltration: A Pan-Cancer Analysis

Background: Serpin peptidase inhibitor clade H, member 1 (SERPINH1) is a gene encoding a member of the serpin superfamily of serine proteinase inhibitors. The upregulated of SERPINH1 was associated with poor prognosis in breast cancer, stomach adenocarcinoma, and esophageal carcinoma. However, the role of SERPINH1 in pan-cancer is largely unexplored.Methods: SERPINH1 expression and the correlation with prognosis in human pan-cancer were analyzed by the Cancer Genome Atlas and the Genotype-Tissue Expression dataset. Pearson correlation analysis was applied to evaluate the role of SERPINH1 expression in tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), DNA methyltransferase, and common immunoregulators. Spearman’s correlation test was used to analysis SERPINH1 expression in tumor immune infiltration and infiltrating immune cells via the Tumor Immune Evaluation Resource database. Furtherly, immunohistochemistry staining of SERPINH1 was acquired from the Human Protein Atlas database for validation.Results: SERPINH1 was abnormally expressed in fourteen cancers. The high expression of SERPINH1 significantly reduced the overall survival (OS), disease-specific survival, and progression free interval in eleven cancers. Moreover, SERPINH1 expression was correlated with MMR, MSI, TMB, and DNA methylation in multiple types of cancer. Also, SERPINH1 expression showed strong association with immunoregulators and immune checkpoint markers in testicular germ cell tumors, brain lower grade glioma (LGG), pheochromocytoma and paraganglioma. In addition, SERPINH1 expression was related to immune cell infiltration in multiple cancers, particularly in breast invasive carcinoma, LGG, and liver hepatocellular carcinoma. The result of immunohistochemistry verification shown that SERPINH1 staining was higher in tumor samples than in normal tissue in colon adenocarcinoma, head and neck squamous cell carcinoma, kidney renal papillary cell carcinoma and cervical squamous cell carcinoma, which was consistent with the result of OS.Conclusion: Overall, these results indicate that SERPINH1 may serve as an important prognostic biomarker and correlate with tumor immunity in human pan-cancer.

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Acetyl Coenzyme A Synthase 2 Acts as a Prognostic Biomarker Associated with Immune Infiltration in Cervical Squamous Cell Carcinoma

Cancers ◽

10.3390/cancers13133125 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3125

Author(s):

Chia-Jung Li ◽

Yi-Han Chiu ◽

Chung Chang ◽

Yuan-chin Ivan Chang ◽

Jim Jinn-Chyuan Sheu ◽

...

Keyword(s):

Cervical Cancer ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Coenzyme A ◽

Prognostic Biomarker ◽

Cervical Squamous Cell Carcinoma ◽

Acetyl Coenzyme A ◽

Immune Infiltration ◽

Acetyl Coenzyme A Synthase

Cervical squamous cell carcinoma (CESC) is one of the most common malignant tumors in women worldwide with a low survival rate. Acetyl coenzyme A synthase 2 (ACSS2) is a conserved nucleosidase that converts acetate to acetyl-CoA for energy production. Our research intended to identify the correlations of ACSS2 with clinical prognosis and tumor immune infiltration in CESC. ACSS2 is highly expressed in many tumors and is involved in the progression and metastasis of these tumors. However, it is not clear how ACSS2 affects CESC progression and immune infiltration. Analysis of the cBioPortal, GEPIA2, UALCAN, and TCGA databases showed that ACSS2 transcript levels were significantly upregulated in multiple cancer types including CESC. Quantitative RT-PCR analysis confirmed that ACSS2 expression was significantly upregulated in human cervical cancer cells. Here, we performed tissue microarray analysis of paraffin-embedded tissues from 240 cervical cancer patients recorded at FIGO/TNM cancer staging. The results showed that ACSS2 and PDL1 were highly expressed in human CESC tissues, and its expression was associated with the clinical characteristics of CESC patients. TIMER database analysis showed that ACSS2 expression in CESC was associated with tumor infiltration of B cells, CD4+ and CD8+ T cells, and cancer-associated fibroblasts (CAF). Kaplan–Meier survival curve analysis showed that CESC with high ACSS2 expression was associated with shorter overall survival. Collectively, our findings establish ACSS2 as a potential diagnostic and prognostic biomarker for CESC.

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DOCK8 Serves as a Prognostic Biomarker and Is Related to Immune Infiltration in Patients With HPV Positive Head and Neck Squamous Cell Carcinoma

Cancer Control ◽

10.1177/10732748211011951 ◽

2021 ◽

Vol 28 ◽

pp. 107327482110119

Author(s):

Zeying Zhang ◽

Yandong Bao ◽

Lu Zhou ◽

Yanling Ye ◽

Weineng Fu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Immune Cell ◽

Neck Squamous Cell Carcinoma ◽

Biological Processes ◽

Immune Infiltration ◽

Favorable Prognosis

Purpose: Dedicator of cytokinesis 8 (DOCK8) was reported to have a vital link to immunoregulation. However, the mechanisms by which it drives immune infiltration in cancer remain uncertain. We tried to assess the role of DOCK8 in patients with cancer, especially human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC). Methods: Data on the expression and survival of DOCK8 in patients with various cancers were analyzed using the Oncomine and TIMER databases. The TIMER database assessed the relationship of DOCK8 with immune infiltration levels and various markers of multiple immune cells. Gene set enrichment analysis revealed tumor-associated biological processes related to DOCK8. ENCODE database was used to explore relevant transcription factors of DOCK8, and a PPI network was constructed using GENEMINIA. The expression and survival role of DOCK8 was confirmed in patients from independent GEO datasets. Results: We determined that DOCK8 expression was upregulated or downregulated in various cancers unlike in healthy tissues. A high expression of DOCK8 was significantly correlated with a favorable prognosis in HPV-positive HNSCC and lung adenocarcinoma (LUAD). Furthermore, multivariate Cox regression analysis revealed that DOCK8 was an independent prognostic factor of HPV-positive HNSCC. Additionally, elevated DOCK8 expression was positively correlated with multiple immune cell infiltration levels and immune marker expression associated with particular immune cell subsets. Also, 14 pathways involved in immune activities and carcinogenesis, 22 potential TFs, and co-expression proteins of DOCK8 indicated DOCK8 to be related to tumor-associated biological processes. Ultimately, we verified that DOCK8 is upregulated and confers a favorable overall survival and progression-free survival status in patients with HPV-positive HNSCC. Conclusion: These results elucidate that high expression of DOCK8 indicates a favorable prognosis in patients with HPV-positive HNSCC as well as increased microenvironmental immune infiltration levels. It would provide new insights into the prognosis predicting and clinical regimen decision making in patients with HPV-positive HNSCC.

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Prognostic And Immunological Implications of BTK Expression In Pan-Cancer

10.21203/rs.3.rs-876071/v1 ◽

2021 ◽

Author(s):

Tao Yang ◽

Lizheng Hao ◽

Jian Chen ◽

Xueying Zhu ◽

Keyi Sun ◽

...

Keyword(s):

Gene Expression ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Molecular Mechanisms ◽

B Cell Lymphoma ◽

Gene Set Enrichment Analysis ◽

Lower Grade ◽

Cox Analysis ◽

Pan Cancer

Abstract Background: Cancer poses a serious threat to human health. Clarifying the potential significance of Bruton's tyrosine kinase (BTK)in cancer has potential clinical value. This study examined the prognostic and immunological value of BTK gene expression in pan-cancer.Methods: We evaluated the gene expression of BTK in tumor tissues and normal tissues in different cancers. Survival analysis, including Kaplan–Meier analysis and Cox analysis, were performed to explore the prognostic value of BTK for pan-cancer based on survival data from The Cancer Genome Atlas (TCGA) database. Spearman’s method was conducted to analyze the interrelation between BTK gene expression and tumor mutational burden (TMB)and microsatellite instability (MSI). We explored the association of BTK expression with the tumor microenvironment based on Estimation of STromal and Immune cells in MAlignant Tumour tissues using Expression data (ESTIMATE) algorithm. Co-expression analysis of BTK expression and immune-related genes was performed. We used Gene Set Enrichment Analysis (GSEA) to examine the molecular mechanisms and pathways of BTK in pan-cancer.Results: High BTK expression in cervical squamous cell carcinoma and endocervical adenocarcinoma (CSEC), head and neck squamous cell carcinoma (HNSC), lung adenocarcinoma (LUAD) and skin cutaneous melanoma (SKCM) was positively correlated with patient prognosis, while high expression of BTK in lymphoid neoplasm diffuse large B cell lymphoma (DLBC), brain lower grade glioma (LGG) and esophageal carcinoma (ESCA) corresponded with a worse prognosis. Cox analysis showed that BTK was closely associated to the prognosis of HNSC, LGG, SKCM and LUAD. BTK expression was correlated with clinical stage, TMB and MSI of 10 types of tumors. In HNSC, LGG, LUAD and SKCM, the expression of BTK was positive correlated with immune and stromal scores. Conclusion: BTK expression can act as a prognostic factor in various cancers, especially in HNSC, LGG, LUAD and SKCM, and this may be from its close association with TMB, MSI and immune cell infiltration.

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Identification of NUTF2 as a Candidate Diagnostic and Prognostic Biomarker Associated with Immune Infiltration in Head and Neck Squamous Cell Carcinoma

OncoTargets and Therapy ◽

10.2147/ott.s337469 ◽

2021 ◽

Vol Volume 14 ◽

pp. 5455-5467

Author(s):

Rui Zhang ◽

Ying Gao

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Prognostic Biomarker ◽

Neck Squamous Cell Carcinoma ◽

Immune Infiltration

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Hypomethylation and downregulation of miR-23b-3p are associated with upregulated PLAU: a diagnostic and prognostic biomarker in head and neck squamous cell carcinoma

Cancer Cell International ◽

10.1186/s12935-021-02251-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zirong Huo ◽

Xiaoguang Li ◽

Jieyu Zhou ◽

Yuqin Fan ◽

Zhentao Wang ◽

...

Keyword(s):

Dna Methylation ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Signaling Pathways ◽

Squamous Cell ◽

Prognostic Biomarker ◽

Neck Squamous Cell Carcinoma ◽

Dna Hypomethylation

Abstract Background DNA methylation and miRNA-target genes play an important part in the early development of various tumors and have been studied as tumor biomarkers. Although previous studies have reported a cluster of molecular events (such as aberrant alterations of genomics and epigenetics), little is known of the potential biomarkers for early diagnosis and prognostic evaluation in head and neck squamous cell carcinoma (HNSCC). Methods Multiple bioinformatics tools based on The Cancer Genome Atlas (TCGA) database and clinical samples were applied to evaluate the beneficial biomarkers in HNSCC. We focused on the role of plasminogen activator urokinase (PLAU), including diagnostic and prognostic significance, gene expression analysis, aberrant DNA methylation characteristics, interaction of miRNAs and associated signaling pathways. Results We found that PLAU was aberrantly upregulated in HNSCC, regardless of the mRNA or protein level. The results of receiver operating characteristic (ROC) curve and Cox regression analysis revealed that PLAU was a diagnostic and independent prognostic factor for patients with HNSCC. Hypomethylation of PLAU was closely related to poor survival in HNSCC. Additionally, miR-23b-3p was predicted to target PLAU and was significantly downregulated in HNSCC tissues. Therefore, our findings suggested that PLAU functioned as a promoter in the pathological process of HNSCC. DNA hypomethylation and downregulation of miR-23b-3p were associated with PLAU overexpression. Finally, our findings provided evidence of a significant interaction between PLAU-target and miRNAs-target pathways, indicating that miR-23b-3p suppresses malignant properties of HNSCC by targeting PLAU via Ras/MAPK and Akt/mTOR signaling pathways. Conclusions PLAU is overexpressed and may serve as an independent diagnostic and prognostic biomarker in HNSCC. Hypomethylation and downregulation of miR-23b-3p might account for the oncogenic role of PLAU in HNSCC.

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