Journal Article

DKFZ-2023-00385

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Bovine meat and milk factor protein expression in tumor-free mucosa of colorectal cancer patients coincides with macrophages and might interfere with patient survival.

Nikitina, E. (First author)DKFZ* ; Burk-Körner, A. (First author)DKFZ* ; Wiesenfarth, M.DKFZ* ; Alwers, E.DKFZ* ; Heide, D.DKFZ* ; Tessmer, C.DKFZ* ; Ernst, C.DKFZ* ; Krunic, D.DKFZ* ; Schrotz-King, P.DKFZ* ; Chang-Claude, J.DKFZ* ; von Winterfeld, M. ; Herpel, E. ; Brobeil, A. ; Brenner, H.DKFZ* ; Heikenwälder, M.DKFZ* ; Hoffmeister, M.DKFZ* ; Kopp-Schneider, A.DKFZ* ; Bund, T. (Last author)DKFZ*

2024
John Wiley & Sons, Inc. Hoboken, NJ

This record in other databases:  

Please use a persistent id in citations: doi:10.1002/1878-0261.13390

Abstract: Bovine milk and meat factors (BMMFs) are plasmid-like DNA molecules isolated from bovine milk and serum, as well as the peritumor of colorectal cancer (CRC) patients. BMMFs have been proposed as zoonotic infectious agents and drivers of indirect carcinogenesis of CRC, inducing chronic tissue inflammation, radical formation and increased levels of DNA damage. Data on expression of BMMFs in large clinical cohorts to test an association with co-markers and clinical parameters were not previously available and were therefore assessed in this study. Tissue sections with paired tumor-adjacent mucosa and tumor tissues of CRC patients [individual cohorts and tissue microarrays (TMAs) (n = 246)], low-/high-grade dysplasia (LGD/HGD) and mucosa of healthy donors were used for immunohistochemical quantification of the expression of BMMF replication protein (Rep) and CD68/CD163 (macrophages) by co-immunofluorescence microscopy and immunohistochemical scoring (TMA). Rep was expressed in the tumor-adjacent mucosa of 99% of CRC patients (TMA), was histologically associated with CD68+ /CD163+ macrophages and was increased in CRC patients when compared to healthy controls. Tumor tissues showed only low stromal Rep expression. Rep was expressed in LGD and less in HGD but was strongly expressed in LGD/HGD-adjacent tissues. Albeit not reaching statistical significance, incidence curves for CRC-specific death were increased for higher Rep expression (TMA), with high tumor-adjacent Rep expression being linked to the highest incidence of death. BMMF Rep expression might represent a marker and early risk factor for CRC. The correlation between Rep and CD68 expression supports a previous hypothesis that BMMF-specific inflammatory regulations, including macrophages, are involved in the pathogenesis of CRC.

Keyword(s): bovine meat and milk factors ; chronic inflammation ; colorectal cancer ; infectious indirect carcinogenesis

Note: #EA:F200#LA:F200# / 2024 May;18(5):1076-1092

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Contributing Institute(s):

1. Arbeitsgruppe Episomal-Persistierende DNA in Krebs- und chron. Erkrankungen (F200)
2. C060 Biostatistik (C060)
3. C070 Klinische Epidemiologie und Alternf. (C070)
4. Chronische Entzündung und Krebs (F180)
5. Monoklonale Antikörper (W170)
6. Lichtmikroskopie (W210)
7. Präventive Onkologie (C120)
8. C020 Epidemiologie von Krebs (C020)
9. DKTK HD zentral (HD01)

Research Program(s):

1. 316 - Infektionen, Entzündung und Krebs (POF4-316) (POF4-316)

Appears in the scientific report 2023

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