Soluble HLA-G expression levels and HLA-G/irinotecan association in metastatic colorectal cancer treated with irinotecan-based strategy.

Lucia Scarabel, Marica Garziera, Sara Fortuna, Fioretta Asaro, Giuseppe Toffoli, Silvano Geremia

Journal: Scientific reports 2020;10(1):8773

PMID: 32471996

Free Full Text on Nature Publishing Group View on PubMed

Abstract

We here explore the soluble Human Leukocyte Antigen-G (sHLA-G) expression level as clinical biomarker in metastatic colorectal cancer (mCRC). To this aim the sHLA-G protein was measured in plasma samples of 40 patients with mCRC treated with the FOLFIRI (irinotecan (CPT-11) plus 5-fluorouracil (5-FU) and leucovorin (LV)) regimen. The results suggest a link between HLA-G levels and irinotecan (CPT-11) pharmacokinetic, leading to hypothesize a molecular interaction between sHLA-G and CPT-11. This interaction was confirmed experimentally by fluorescence spectroscopy. HLA-G is known to exist in a number of polymorphs that affect both the protein expression levels and its peptide-binding cleft. The interaction between HLA-G polymorphs and CPT-11 was explored by means of computational modelling, confirming the hypothesis that CPT-11 could actually target the peptide binding cleft of the most common HLA-G polymorphs.

Address: Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico (CRO), IRCCS, 33081, Aviano, Italy.; Department of Chemical and Pharmaceutical Sciences, University of Trieste, Via L. Giorgieri 1, 34127, Trieste, Italy. [email protected].; Department of Chemical and Pharmaceutical Sciences, University of Trieste, Via L. Giorgieri 1, 34127, Trieste, Italy.

DOI: 10.1038/s41598-020-65424-z

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https://medlineplus.gov/colorectalcancer.html

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https://antibodies.cancer.gov/detail/CPTC-HLA-DQA1...

MeSH Terms: Adenocarcinoma, Aged, Antigens, Neoplasm, Antineoplastic Combined Chemotherapy Protocols, Binding Sites, Camptothecin, Colorectal Neoplasms, Female, Fluorouracil, HLA-G Antigens, Humans, Irinotecan, Leucovorin, Male, Middle Aged, Models, Molecular, Protein Binding, Protein Conformation, Protein Isoforms, Solubility, Spectrometry, Fluorescence