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dc:titleProinflammatory Microenvironment in Adenocarcinoma Tissue of Colorectal Carcinoma
dc:creatorTodorovic, Slobodan
dc:creatorS. Ćeranić, Miljan
dc:creatorTošković, Borislav
dc:creatorDiklić, Miloš
dc:creatorMitrovic Ajtic, Olivera
dc:creatorSuboticki, Tijana
dc:creatorVukotic, Milica
dc:creatorDragojevic, Teodora
dc:creatorŽivković, Emilija
dc:creatorOprić, Svetlana
dc:creatorStojiljkovic, Miodrag
dc:creatorGačić, Jasna
dc:creatorČolaković, Nataša
dc:creatorCrnokrak, Bogdan
dc:creatorČokić, Vladan
dc:creatorĐikić, Dragoslava
dc:subjectcolorectal adenocarcinoma
dc:subjecttumor microenvironment
dc:subjectinflammation
dc:subjectNF-κB signaling
dc:subjectinterleukin-6
dc:subjectS-100 protein
dc:subjectoxidative stress
dc:subject8-hydroxy-2'-deoxyguanosine
dc:subjectnitrotyrosine
dc:subjectβ-catenin
dc:subjectMUC2
dc:subjectCA19-9
dc:subjectmTOR signaling
dc:subjectKi-67
dc:subjecttumor cell proliferation
dc:subjectmetastasis
dc:subjectprognosis
dc:subjectintestinal differentiation
dc:descriptionCancer-promoting proinflammatory microenvironment influences colorectal cancer (CRC) development. We examined the biomarkers of inflammation, intestinal differentiation, and DNA activity correlated with the clinical parameters to observe progression and prognosis in the adenocarcinoma subtype of CRC. Their immunohistology, immunoblotting, and RT-PCR analyses were performed in the adenocarcinoma and neighboring healthy tissues of 64 patients with CRC after routine colorectal surgery. Proinflammatory nuclear factor kappa B (NFκB) signaling as well as interleukin 6 (IL-6) and S100 protein levels were upregulated in adenocarcinoma compared with nearby healthy colon tissue. In contrast to nitrotyrosine expression, the oxidative stress marker 8-Hydroxy-2'-deoxyguanosine (8-OHdG) was increased in adenocarcinoma tissue. Biomarkers of intestinal differentiation β-catenin and mucin 2 (MUC2) were inversely regulated, with the former upregulated in adenocarcinoma tissue and positively correlated with tumor marker CA19-9. Downregulation of MUC2 expression correlated with the increased 2-year survival rate of patients with CRC. Proliferation-related mammalian target of rapamycin (mTOR) signaling was activated, and Ki67 frequency was three-fold augmented in positive correlation with metastasis and cancer stage, respectively. Conclusion: We demonstrated a parallel induction of oxidative stress and inflammation biomarkers in adenocarcinoma tissue that was not reflected in the neighboring healthy colon tissue of CRC. The expansiveness of colorectal adenocarcinoma was confirmed by irregular intestinal differentiation and elevated proliferation biomarkers, predominantly Ki67. The origin of the linked inflammatory factors was in adenocarcinoma tissue, with an accompanying systemic immune response.
dc:publisherBasel : MDPI
dc:date2024
dc:typeinfo:eu-repo/semantics/article
dc:typeinfo:eu-repo/semantics/publishedVersion
dc:identifierhttps://stomatoloskifakultet.rs/nauka/publikacija/810
dc:identifierDOI 10.3390/ijms251810062
dc:identifierISSN 1422-0067
dc:sourceInternational Journal of Molecular Sciences 25(18): 10062
dc:languageen
dc:rightsinfo:eu-repo/semantics/closedAccess
dc:rightsSva prava zadržana