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 harbourPIK3CAandEP300mutations. 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 asCD276) andNT5E(also known asCD73) andPD-L2(also known asPDCD1LG2). 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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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 29. Sept. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chakravarthy, Ankur [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2020.04.02.019711 |
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| PPN (Katalog-ID): |
XBI000843180 |
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| 245 | 1 | 0 | |a Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance |
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| 520 | |a 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 harbourPIK3CAandEP300mutations. 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 asCD276) andNT5E(also known asCD73) andPD-L2(also known asPDCD1LG2). 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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| 700 | 1 | |a Jeyakumar, Maxmilan |4 aut | |
| 700 | 1 | |a Rodriguez, Daniela Rothschild |4 aut | |
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| 700 | 1 | |a McDermott, Jacqueline |4 aut | |
| 700 | 1 | |a Su, Xiaoping |4 aut | |
| 700 | 1 | |a Egawa, Nagayasau |4 aut | |
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| 700 | 1 | |a Skingen, Vilde Eide |4 aut | |
| 700 | 1 | |a Halle, Mari Kyllesø |4 aut | |
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| 700 | 1 | |a Sprung, Susanne |4 aut | |
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| 700 | 1 | |a Fenton, Tim R |0 (orcid)0000-0002-4737-8233 |4 aut | |
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