Pan-Cancer Molecular Patterns and Biological Implications Associated with a Tumor-Specific Molecular Signature

Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Católica de Córdoba, Córdoba X5016DHK, Argentina

Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba X5000HUA, Argentina

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Facultad de Matemática, Astronomía y Física, Universidad Nacional de Córdoba, Córdoba X5000HUA, Argentina

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Laboratorio de Terapia Molecular y Celular—Genocan, Fundación Instituto Leloir, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires C1405BWE, Argentina

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Instituto Académico Pedagógico de Ciencias Básicas y Aplicadas, Universidad Nacional de Villa María, Villa María, Córdoba X5900, Argentina

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Laboratorio de Inmuno Oncología Traslacional, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires C1428ADN, Argentina

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Centro de Investigaciones en Bioquímica Clínica e Inmunología, Consejo Nacional de Investigaciones Científicas y Técnicas, Córdoba X5000HUA, Argentina

Author to whom correspondence should be addressed.

Cells 2021, 10(1), 45; https://doi.org/10.3390/cells10010045

Received: 7 November 2020 / Revised: 25 November 2020 / Accepted: 26 November 2020 / Published: 31 December 2020

(This article belongs to the Special Issue 10th Anniversary of Cells—Advances in Cell Signaling and Regulated Cell Death)

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Abstract

Studying tissue-independent components of cancer and defining pan-cancer subtypes could be addressed using tissue-specific molecular signatures if classification errors are controlled. Since PAM50 is a well-known, United States Food and Drug Administration (FDA)-approved and commercially available breast cancer signature, we applied it with uncertainty assessment to classify tumor samples from over 33 cancer types, discarded unassigned samples, and studied the emerging tumor-agnostic molecular patterns. The percentage of unassigned samples ranged between 55.5% and 86.9% in non-breast tissues, and gene set analysis suggested that the remaining samples could be grouped into two classes (named C1 and C2) regardless of the tissue. The C2 class was more dedifferentiated, more proliferative, with higher centrosome amplification, and potentially more TP53 and RB1 mutations. We identified 28 gene sets and 95 genes mainly associated with cell-cycle progression, cell-cycle checkpoints, and DNA damage that were consistently exacerbated in the C2 class. In some cancer types, the C1/C2 classification was associated with survival and drug sensitivity, and modulated the prognostic meaning of the immune infiltrate. Our results suggest that PAM50 could be repurposed for a pan-cancer context when paired with uncertainty assessment, resulting in two classes with molecular, biological, and clinical implications. View Full-Text

Keywords: tumor-agnostic classification; PAM50; uncertainty assessment; gene expression; cell-cycle

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MDPI and ACS Style

Rocha, D.; García, I.A.; González Montoro, A.; Llera, A.; Prato, L.; Girotti, M.R.; Soria, G.; Fernández, E.A. Pan-Cancer Molecular Patterns and Biological Implications Associated with a Tumor-Specific Molecular Signature. Cells 2021, 10, 45. https://doi.org/10.3390/cells10010045

AMA Style

Rocha D, García IA, González Montoro A, Llera A, Prato L, Girotti MR, Soria G, Fernández EA. Pan-Cancer Molecular Patterns and Biological Implications Associated with a Tumor-Specific Molecular Signature. Cells. 2021; 10(1):45. https://doi.org/10.3390/cells10010045

Chicago/Turabian Style

Rocha, Darío, Iris A. García, Aldana González Montoro, Andrea Llera, Laura Prato, María R. Girotti, Gastón Soria, and Elmer A. Fernández. 2021. "Pan-Cancer Molecular Patterns and Biological Implications Associated with a Tumor-Specific Molecular Signature" Cells 10, no. 1: 45. https://doi.org/10.3390/cells10010045

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Pan-Cancer Molecular Patterns and Biological Implications Associated with a Tumor-Specific Molecular Signature

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