Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance.

Abstract Human papillomavirus (HPV)-associated cervical cancer represents one of the leading causes of cancer death worldwide. Although low-middle income countries are disproportionately affected, our knowledge of the disease predominantly originates from populations in high-income countries. Using the largest multi-omic analysis of cervical squamous cell carcinoma (CSCC) to date, totalling 643 tumours and representing patient populations from the USA, Europe and Sub-Saharan Africa, we identify two CSCC subtypes (C1 and C2) with differing prognosis. C1 tumours are largely HPV16-driven, display increased cytotoxic T-lymphocyte infiltration and frequently harbour PIK3CA and EP300 mutations. C2 tumours are associated with shorter overall survival, are frequently driven by HPVs from the HPV18-containing alpha-7 clade, harbour alterations in the Hippo signalling pathway and increased expression of immune checkpoint genes, B7-H3 (also known as CD276) and NT5E (also known as CD73) and PD-L2 (also known as PDCD1LG2). In conclusion, we identify two novel, therapy-relevant CSCC subtypes that share the same defining characteristics across three geographically diverse cohorts.

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Integrated Analysis Reveals ENDOU as a Biomarker in Head and Neck Squamous Cell Carcinoma Progression

Frontiers in Oncology ◽

10.3389/fonc.2020.522332 ◽

2021 ◽

Vol 10 ◽

Author(s):

Chengzhi Xu ◽

Yunbin Zhang ◽

Yupeng Shen ◽

Yong Shi ◽

Ming Zhang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Prognostic Significance ◽

Neck Squamous Cell Carcinoma ◽

Integrated Analysis ◽

Pathway Enrichment Analysis ◽

And Migration ◽

Proliferation And Migration

BackgroundHead and neck squamous cell carcinoma (HNSCC) is a leading cancer with high morbidity and mortality worldwide. The aim is to identify genes with clinical significance by integrated bioinformatics analysis and investigate their function in HNSCC.MethodsWe downloaded and analyzed two gene expression datasets of GSE6631 and GSE107591 to screen differentially expressed genes (DEGs) in HNSCC. Common DEGs were functionally analyzed by Gene ontology and KEGG pathway enrichment analysis. Protein-protein interaction (PPI) network was constructed with STRING database and Cytoscape. ENDOU was overexpressed in FaDu and Cal-27 cell lines, and cell proliferation and migration capability were evaluated with MTT, scratch and transwell assay. The prognostic performance of ENDOU and expression correlation with tumor infiltrates in HNSCC were validated with TCGA HNSCC datasets.ResultsNinety-eight genes shared common differential expression in both datasets, with core functions like extracellular matrix organization significantly enriched. 15 genes showed prognostic significance, and COBL and ENDOU serve as independent survival markers in HNSCC. In-vitro ENDOU overexpression inhibited FaDu and Cal-27 cells proliferation and migration, indicating its tumor-suppressing role in HNSCC progression. GSEA analysis indicated ENDOU down-stream pathways like DNA replication, mismatch repair, cell cycle and IL-17 signaling pathway. ENDOU showed relative lower expression in HNSCC, especially HPV-positive HNSCC samples. At last, ENDOU showed negative correlation with tumor purity and tumor infiltrating macrophages, especially M2 macrophages.ConclusionThis study identified ENDOU as a biomarker with prognostic significance in HNSCC progression.

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Prognostic significance of the Fas-receptor/Fas-ligand system in cervical squamous cell carcinoma

Virchows Archiv ◽

10.1007/s00428-007-0535-z ◽

2007 ◽

Vol 452 (1) ◽

pp. 65-74 ◽

Cited By ~ 9

Author(s):

Enrique Lerma ◽

Marisa Romero ◽

Alberto Gallardo ◽

Cristina Pons ◽

Josefina Muñoz ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Fas Ligand ◽

Prognostic Significance ◽

Cervical Squamous Cell Carcinoma ◽

Fas Receptor ◽

Ligand System

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Prognostic significance of CD24 protein expression in patients treated with adjuvant radiotherapy after radical hysterectomy for cervical squamous cell carcinoma

Radiotherapy and Oncology ◽

10.1016/j.radonc.2010.01.007 ◽

2010 ◽

Vol 95 (3) ◽

pp. 359-364 ◽

Cited By ~ 8

Author(s):

Chang Ohk Sung ◽

Won Park ◽

Yoon-La Choi ◽

Geunghwan Ahn ◽

Sang Yong Song ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Protein Expression ◽

Cell Carcinoma ◽

Squamous Cell ◽

Radical Hysterectomy ◽

Adjuvant Radiotherapy ◽

Prognostic Significance ◽

Cervical Squamous Cell Carcinoma

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Prognostic significance of histone methyltransferase enhancer of zeste homolog 2 in patients with cervical squamous cell carcinoma

Oncology Letters ◽

10.3892/ol.2015.3319 ◽

2015 ◽

Vol 10 (2) ◽

pp. 857-862 ◽

Cited By ~ 8

Author(s):

MINFEI JIN ◽

ZUJING YANG ◽

WEIPING YE ◽

XIAOWEI YU ◽

XIAOLIN HUA

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Prognostic Significance ◽

Cervical Squamous Cell Carcinoma ◽

Histone Methyltransferase ◽

Enhancer Of Zeste

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HIF1α and SOX2 expression in cervical squamous cell carcinoma

Vojnosanitetski pregled ◽

10.2298/vsp171213043m ◽

2019 ◽

Vol 76 (12) ◽

pp. 1253-1260

Author(s):

Svetlana Milenkovic ◽

Tatjana Terzic ◽

Boris Vranes ◽

Ivan Soldatovic

Keyword(s):

Squamous Cell Carcinoma ◽

Lymph Nodes ◽

Cell Carcinoma ◽

Squamous Cell ◽

Hypoxia Inducible Factor ◽

Prognostic Significance ◽

Tumor Grade ◽

Cervical Squamous Cell Carcinoma ◽

Histopathological Analysis ◽

Significant Difference

Background/Aim. Hypoxia is one of the major changes that occurs in the tumor microenvironment. It has been observed that there are pluripotent cancer cells in the cancer cell population that affect tumor growth and their resistance to therapy. The aim of this study was to examine the expression of hypoxia-inducible factor-1 alpha (HIF-1?), endogenous marker of hypoxia, and SOX2, marker of the pluripotent stem cells existing in the normal adult tissues, in the cervical squamous cell carcinoma (SCC). Methods. The study was conducted in 90 women with invasive cervical SCC, divided into two groups ? 60 women in the Group A, with FIGO IB1 < 20 mm tumors (no metastases in the lymph nodes), and 30 women in the group B with tumors FIGO I?II (positive lymph nodes). The basic clinical parameters were determined by standard histopathological analysis, and the expression of HIF-1? and SOX2 by immunohistochemical examination. Results. There was a significant difference between the groups A and B, in the expression of HIF-1? (p = 0.024), but not in the expression of SOX2 (p = 0.566). Expression of HIF-1? was significantly higher in the group with lymph node metastases and invasion of lymphovascular spaces (p <0.001) but not associated with tumor size (p = 0.291) or lymphocytic stromal response (p = 0.940). The tumor grade significantly influenced the expression of HIF-1? (p = 0.013). The expression of SOX2 did not significantly correlate with any of the established clinical tumor parameters. Conclusion. A significant difference in the expression of HIF-1 ? between the group with and that without metastases in lymph nodes in invasive cervical SCC could distinguish HIF-1? as a parameter of poor prognosis of the disease. The prognostic significance of SOX2 as well as a significant correlation between expression of HIF-1? and SOX2 were not established.

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