The prognostic role of HIF-1? and NF-?B expression in RAS wild-type metastatic colorectal cancer: A Turkish Oncology Group (TOG) study

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dc.contributor.authorDemirkiran, Aykut
dc.contributor.authorKilinc, Fahriye
dc.contributor.authorKocak, Mehmet Zahid
dc.contributor.authorDemirkiran, Deniz
dc.contributor.authorKorkmaz, Mustafa
dc.contributor.authorEryilmaz, Melek Karakurt
dc.contributor.authorAraz, Murat
dc.date.accessioned2024-02-23T13:43:51Z
dc.date.available2024-02-23T13:43:51Z
dc.date.issued2023
dc.departmentNEÜen_US
dc.description.abstractBackground Not all RAS wild-type metastatic colorectal cancer (mCRC) patients experience the same benefit from anti-epidermal growth factor receptor (EGFR) treatments. Studies have shown that nuclear factor-kappa B (NF-kappa B), hypoxia-inducible factor-1 alpha (HIF-1 alpha), interleukin 8 (IL-8) and transforming growth factor beta (TGF-beta) may be therapeutic targets for mCRC. The aim of this study was to clarify the prognostic value of NF-kappa B, HIF-1 alpha, IL-8, and TGF-beta expression in patients with left-sided mCRC receiving EGFR inhibitors. Methods Patients with RAS wild-type, left-sided mCRC treated with anti-EGFR on the first line between September 2013 and April 2022 were included. Immunohistochemical staining for NF-kappa B, HIF-1 alpha, IL-8 and TGF-beta was performed from tumor tissues of 88 patients. Patients were divided into NF-kappa B, HIF-1 alpha, IL-8 and TGF-beta expression positive and negative group, moreover, expression positive group were also divided into two group as expression intensity low and high group. The median follow-up was 25.2 months. Results Median progression-free survival (PFS) was 8.1 (6-10.2) months in the cetuximab group, 11.3 (8.5-14) months in the panitumumab group (p = 0.09). Median overall survival (OS) was 23.9 (4.3-43.4) months in the cetuximab group, 26.9 (15.9-31.9) months in the panitumumab group (p = 0.8). Cytoplasmic NF-kappa B expression was present in all patients. The mOS was 19.8 (11-28.6) months in NF-kappa B expression intensity low group and 36.5 (20.1-52.8) months in high group (p = 0.03). The mOS of the HIF-1 alpha expression negative group was significantly longer compared with expression positive group (p = 0.014). There was no significant difference in IL-8 and TGF-beta expression status on mOS and mPFS (for all, p > 0.05). Positive expression of HIF-1 alpha was poor prognostic for mOS in the univariate analysis (HR:2.7, 95% CI 1.18-6.52, p = 0.02) and in multivariate analysis (HR 3.69, 95% CI 1.41-9.6, p = 0.008). High cytoplasmic expression intensity of NF-kappa B was found to have a good prognostic value for mOS (HR 0.47, 95% CI 0.26-0.85, p = 0.01). Conclusion High cytoplasmic expression intensity of NF-kappa B and negative expression of HIF-1 alpha could be a good prognostic marker for mOS in RAS wild-type left-sided mCRC.en_US
dc.description.sponsorshipScientific Research Projects (BAP) unit of Necmettin Erbakan Universityen_US
dc.description.sponsorshipThis study is funded by Scientific Research Projects (BAP) unit of Necmettin Erbakan Universityen_US
dc.identifier.doi10.1007/s00432-023-04628-y
dc.identifier.issn0171-5216
dc.identifier.issn1432-1335
dc.identifier.pmid36808300en_US
dc.identifier.scopus2-s2.0-85148423768en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1007/s00432-023-04628-y
dc.identifier.urihttps://hdl.handle.net/20.500.12452/10950
dc.identifier.wosWOS:000936500000001en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.relation.ispartofJournal Of Cancer Research And Clinical Oncologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectRas Wilden_US
dc.subjectAnti-Egfren_US
dc.subjectSurvivalen_US
dc.subjectHif-1 Alphaen_US
dc.subjectNf-Kappa Ben_US
dc.titleThe prognostic role of HIF-1? and NF-?B expression in RAS wild-type metastatic colorectal cancer: A Turkish Oncology Group (TOG) studyen_US
dc.typeArticleen_US

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