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C1Q‐TNF‐related peptide 8 (CTRP8) in human prostate cancer

2021· article· en· W3172201792 on OpenAlexafffund
Sai Nivedita Krishnan, Aleksandra Głogowska, Thatchawan Thanasupawat, Leanne Arreza, William B. Wong, Karen S. Sfanos, Bruce J. Trock, M. Bazin, Girish M. Shah, Sabine Hombach‐Klonisch, Thomas Klonisch

Bibliographic record

VenueThe FASEB Journal · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicExtracellular vesicles in disease
Canadian institutionsUniversité LavalUniversity of Manitoba
FundersNatural Sciences and Engineering Research Council of CanadaCancer Research Society
KeywordsProstate cancerBiologyAntiserumCancer researchProstateTissue microarrayCancerImmunohistochemistryPolyclonal antibodiesMolecular biologyAntibodyImmunology

Abstract

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Introduction C1Q Tumor Necrosis Factor related Peptide 8 (CTRP8) is the one of the least characterized members of the C1Q/TNF family of proteins which is engaged in diverse functions ranging from metabolism to immunity and is one of only two CTRP family members absent in the mouse genome. CTRP8 was identified in our lab as a novel ligand of the RXFP1 receptor and was found to promote invasiveness and chemoresistance to temozolomide in glioblastoma (GB)(Glogowska et al., 2013; Thanasupawat et al., 2018). We have generated high‐affinity rabbit antisera to human CTRP8 to identify a selective mast cell subpopulation in human prostate cancer tissues (Hempel Sullivan et al., 2020). Mast cells are innate immune cells which are primarily known for their role in the mediation of allergic responses. They have been detected within prostate cancer tissues and serve as potential prognostic marker in prostate cancer (Johansson et al., 2010; Hempel Sullivan et al., 2020). Methods Affinity‐purified rabbit polyclonal antisera directed against an epitope unique to human CTRP8 were characterized by Western blot, immunofluorescence, and immunohistochemistry in prostate cancer tissue sections and human prostate cancer tissue microarrays (TMAs). Results Of several Flag‐tagged human and mouse CTRP family members transiently expressed in HEK293T cells, the CTRP8 antisera exclusively detected human CTRP8 as assessed by Western blot, demonstrating the specificity of the antisera. We studied the expression of CTRP8 in human prostate tissues. CTRP8 was expressed in a subpopulation of human mast cells distributed in prostate cancer tissues, as demonstrated by co‐localization of CTRP8 immunoreactivity and toluidine blue positive mast cells in prostate cancer tissues. This was further validated by dual immunofluorescence of CTRP8 with Tryptase, a marker for mature mast cells. Initial analysis of prostate cancer tissue microarrays (TMAs) (n= 360) revealed a comparative increase in the proportion of Tryptase+/ CTRP8+ cells versus total number of mast cells (Tryptase+/ CTRP8+ and Tryptase+/ CTRP8‐ cells) in the extra‐tumoral compartment as compared to intra‐tumoral regions for Gleason grades 6 and 7 prostate cancer samples. Weak staining of CTRP8 was detected in prostate epithelial cells. The RXFP1+ human prostate cancer cell line PC3 responded to CTRP8 treatment with increased protein kinase C delta signaling and enhanced motility as determined by real‐time migration assays. Conclusions Here we have identified the expression of adipokine family member CTRP8 in prostate epithelial cells and in a subpopulation of mature mast cells in patient prostate cancer tissues, thus, identifying CTRP8 as a novel player in prostate cancer and associated mast cell compartment. References Glogowska, A., et al. J. Pathol., 231, 466–479, 2013 Thanasupawat, T., et al. Mol. Oncol. 12, 1464–1479, 2018 Johansson, A., Am. J. Pathol, 177, 1031–1041, 2010 Hempel Sullivan H, et al. J. Pathol., 2020 Hempel Sullivan H, et al. Cancer Epidemiol Biomarkers Prev., 2020

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.005
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.265
Teacher spread0.256 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations1
Published2021
Admission routes2
Has abstractyes

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