Chemotherapy-induced cytokines and prognostic gene signatures vary across breast and colorectal cancer.
Academic Article
Overview
abstract
The mechanisms by which chemotherapeutic drugs mediate efficacy and toxicity in patients across cancers are not fully understood. A poorly understood aspect of the tumor cell response to chemotherapy is cytokine regulation. Some drug-induced cytokines promote the anti-cancer activity of the drugs, but others may promote proliferation, metastasis, and drug resistance. We evaluated effects of clinical chemotherapeutics oxaliplatin, cisplatin, 5-fluorouracil (5-FU), doxorubicin, paclitaxel, docetaxel, and carboplatin on a panel of 52 cytokines in MCF7 breast cancer (BC) cells. We observed pan-drug effects, such as the upregulation of TRAIL-R2 and Chitinase 3-like 1 and drug-specific effects on interleukin and CXCL cytokines. We compared cytokine regulation in MCF7 BC and HCT116 colorectal cancer (CRC) cells, revealing tissue-specific drug effects such as enhanced upregulation of TRAIL-R2 and downregulation of IFN-β and TRAIL in MCF7 by cisplatin, oxaliplatin, and 5-FU. We found that chemotherapy-inducible transcripts have varying potential for prognostic significance in CRC versus BC. Among the non-prognostic CRC genes that were prognostic in BC were NFKBIA and GADD45A, both of which support anti-cancer drug mechanisms. Thus, we establish a novel 7-drug, 52-cytokine signature in MCF7 BC cells and a 3-drug, 40-cytokine signature in HCT116 CRC cells that suggest drug-specific and tissue-specific cytokine regulation. Distinct differences across prognostic gene signatures in BC and CRC further support tissue specificity in the relative impact of drug-regulated genes on patient survival.
