Abstract
Anticancer chemotherapy (CT) produces non-desirable effects on normal healthy cells and tissues. Oxaliplatin is widely used in the treatment of colorectal cancer and responsible for the development of sensory neuropathy in varying degrees, from complete tolerance to chronic neuropathic symptoms. We studied the differential gene expression of peripheral leukocytes in patients receiving oxaliplatin-based chemotherapy to find genes and pathways involved in oxaliplatin-induced peripheral neuropathy. Circulating white cells were obtained prior and after three cycles of FOLFOX or CAPOX chemotherapy from two groups of patients: with or without neuropathy. RNA was purified, and transcriptomes were analyzed. Differential transcriptomics revealed a total of 502 genes, which were significantly up- or down-regulated as a result of chemotherapy treatment. Nine of those genes were expressed in only one of two situations: CSHL1, GH1, KCMF1, IL36G and EFCAB8 turned off after CT, and CSRP2, IQGAP1, GNRH2, SMIM1 and C5orf17 turned on after CT. These genes are likely to be associated with the onset of oxaliplatin-induced peripheral neuropathy. The quantification of their expression in peripheral white cells may help to predict non-desirable side effects and, consequently, allow a better, more personalized chemotherapy.
Highlights
Oxaliplatin (OX), a part of FOLFOX chemotherapy (FOL—Folinic acid, leucovorin, F—Fluorouracil, 5-FU) or CAPOX (CA—capecitabine, OX—oxaliplatin) chemotherapy is a widely used anticancer chemotherapy (CT)-agent for colorectal cancer
MRNA copies of Chorionic somatomammotropin hormone-like 1 (CSHL1), GH1, KCMF1, IL36G, and EF-hand calcium binding domain 8 (EFCAB8) genes were found in white cells previous to CT, after three FOLFOX/CAPOX cycles, no message for these genes was detected
Cysteine and glycine-rich protein 2 (CSRP2), IQ motif containing GTPase activating protein 1 (IQGAP1), Gonadotropin-releasing hormone 2 (GNRH2), chromosome 5 open reading frame 17 (C5orf17) and Small integral membrane protein 1 (SMIM1) genes did not show any expression in white cells pre-chemotherapy, but after CT, mRNA specific to them was found
Summary
Oxaliplatin (OX), a part of FOLFOX chemotherapy (FOL—Folinic acid, leucovorin, F—Fluorouracil, 5-FU) or CAPOX (CA—capecitabine, OX—oxaliplatin) chemotherapy is a widely used anticancer chemotherapy (CT)-agent for colorectal cancer. We performed a genome-wide association analysis in a cohort of patients with colon cancer who received oxaliplatin-based combination chemotherapy to try to identify genes associated with severe oxaliplatin-induced chronic peripheral neuropathy (OXPN). This approach can be used to gain information about genes and specific signal transduction pathways involved in peripheral neural toxicity induced by oxaliplatin. The knowledge of selected markers may provide additional information about the differences between patients more or less likely to develop neuropathy This information can be taken into account for alternative colorectal cancer treatment protocols
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