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Elevated expression...
Elevated expression of complement factor I in lung cancer cells associates with shorter survival–Potentially via non-canonical mechanism
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- Felberg, Anna (author)
- Medical University of Gdansk
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- Bieńkowski, Michał (author)
- Medical University of Gdansk
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- Stokowy, Tomasz (author)
- University of Bergen
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- Myszczyński, Kamil (author)
- Medical University of Gdansk
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- Polakiewicz, Zuzanna (author)
- University of Gdansk
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- Kitowska, Kamila (author)
- University of Gdansk
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- Sądej, Rafał (author)
- University of Gdansk
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- Mohlin, Frida (author)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups
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- Kuźniewska, Alicja (author)
- Medical University of Gdansk
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- Kowalska, Daria (author)
- Medical University of Gdansk
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- Stasiłojć, Grzegorz (author)
- Medical University of Gdansk
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- Jongerius, Ilse (author)
- Academic Medical Center of University of Amsterdam (AMC)
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- Spaapen, Robbert (author)
- Academic Medical Center of University of Amsterdam (AMC)
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- Mesa-Guzman, Miguel (author)
- University of Navarra
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- Montuenga, Luis M. (author)
- Health Research Institute of Navarra (IDISNA),University of Navarra,Spanish Center for Biomedical Research Network in Oncology (CIBERONC)
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- Blom, Anna M. (author)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Protein Chemistry, Malmö,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Pio, Ruben (author)
- Health Research Institute of Navarra (IDISNA),Spanish Center for Biomedical Research Network in Oncology (CIBERONC),University of Navarra
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- Okrój, Marcin (author)
- Medical University of Gdansk
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(creator_code:org_t)
- 2024
- 2024
- English 13 s.
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In: Translational Research. - 1931-5244. ; 269, s. 1-13
- Related links:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
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- While numerous membrane-bound complement inhibitors protect the body's cells from innate immunity's autoaggression, soluble inhibitors like complement factor I (FI) are rarely produced outside the liver. Previously, we reported the expression of FI in non-small cell lung cancer (NSCLC) cell lines. Now, we assessed the content of FI in cancer biopsies from lung cancer patients and associated the results with clinicopathological characteristics and clinical outcomes. Immunohistochemical staining intensity did not correlate with age, smoking status, tumor size, stage, differentiation grade, and T cell infiltrates, but was associated with progression-free survival (PFS), overall survival (OS) and disease-specific survival (DSS). Multivariate Cox analysis of low vs. high FI content revealed HR 0.55, 95 % CI 0.32-0.95, p=0.031 for PFS, HR 0.51, 95 % CI 0.25-1.02, p=0.055 for OS, and HR 0.32, 95 % CI 0.12-0.84, p=0.021 for DSS. Unfavorable prognosis might stem from the non-canonical role of FI, as the staining pattern did not correlate with C4d - the product of FI-supported degradation of active complement component C4b. To elucidate that, we engineered three human NSCLC cell lines naturally expressing FI with CRISPR/Cas9 technology, and compared the transcriptome of FI-deficient and FI-sufficient clones in each cell line. RNA sequencing revealed differentially expressed genes engaged in intracellular signaling pathways controlling proliferation, apoptosis, and responsiveness to growth factors. Moreover, in vitro colony-formation assays showed that FI-deficient cells formed smaller foci than FI-sufficient NSCLC cells, but their size increased when purified FI protein was added to the medium. We postulate that a non-canonical activity of FI influences cellular physiology and contributes to the poor prognosis of lung cancer patients.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Complement system
- Immunohistochemistry
- Innate immunity
- Lung cancer
- NSCLC
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Felberg, Anna
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Bieńkowski, Mich ...
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Stokowy, Tomasz
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Myszczyński, Kam ...
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Polakiewicz, Zuz ...
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Kitowska, Kamila
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show more...
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Sądej, Rafał
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Mohlin, Frida
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Kuźniewska, Alic ...
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Kowalska, Daria
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Stasiłojć, Grzeg ...
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Jongerius, Ilse
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Spaapen, Robbert
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Mesa-Guzman, Mig ...
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Montuenga, Luis ...
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Blom, Anna M.
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Pio, Ruben
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Okrój, Marcin
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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Translational Re ...
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Lund University