Prognostic Values of Tissue and Serum Angiogenic Growth Factors Depend on the Phenotypic Subtypes of Colorectal Cancer

Jussi Herman Kasurinen; Jaana Hagström; Tuomas Kaprio; Sirpa Jalkanen; Marko Salmi; Camilla Böckelman; Caj Haglund

doi:10.3390/cancers15153871

Prognostic Values of Tissue and Serum Angiogenic Growth Factors Depend on the Phenotypic Subtypes of Colorectal Cancer

Cancers (Basel). 2023 Jul 29;15(15):3871. doi: 10.3390/cancers15153871.

Authors

Jussi Herman Kasurinen¹, Jaana Hagström^{1

2

3}, Tuomas Kaprio^{1

4}, Sirpa Jalkanen⁵, Marko Salmi⁵, Camilla Böckelman^{1

4}, Caj Haglund^{1

2

4}

Affiliations

¹ Translational Cancer Medicine Research Program, Faculty of Medicine, University of Helsinki, 00100 Helsinki, Finland.
² Department of Pathology, University of Helsinki and Helsinki University Hospital, 00100 Helsinki, Finland.
³ Department of Oral Pathology and Radiology, University of Turku, 20014 Turku, Finland.
⁴ Department of Surgery, University of Helsinki and Helsinki University Hospital, 00100 Helsinki, Finland.
⁵ MediCity Research Laboratory and Institute of Biomedicine, University of Turku, 20014 Turku, Finland.

Abstract

We classified colorectal cancer (CRC) patients into four phenotypic subgroups and investigated the prognostic value of angiogenic growth factors across subgroups. Preoperative serum concentrations and tissue expressions of VEGF, bFGF, and PDGF-bb were determined among 322 CRC patients. We classified patients into phenotypic subgroups (immune, canonical, metabolic, and mesenchymal) according to a method described in our earlier work. Among the metabolic subgroup, patients with high serum concentrations of VEGF, bFGF, or PDGF-bb exhibited a significantly improved prognosis. Moreover, those with high VEGF tissue expressions exhibited a significantly improved prognosis among patients in the metabolic subgroup. Among immune patients, a high VEGF serum expression is associated with a worse prognosis. A high serum bFGF concentration is associated with a favorable prognostic factor among patients with a canonical tumor phenotype. A high PDGF-bb tissue expression is associated with non-metastasized disease and with the immune, canonical, and metabolic subtypes. To our knowledge, this is the first study to show that the prognostic value of angiogenic growth factors differs between phenotypic subtypes.

Keywords: CMS; PDGF-bb; VEGF; bFGF; colon cancer; colorectal cancer; immunohistochemistry; survival; tumor phenotype.

Grants and funding

This research was financially supported by the Competitive State Research Financing of the Expert Responsibility of Helsinki University Hospital, the Finnish Cancer Foundation, Finska Läkaresällskapet, Understödsföreningen Liv och Hälsa, the Sigrid Jusélius Foundation and K Albin Johanssons foundation. Open access funding provided by University of Helsinki.