key: cord-0860363-sp02scpa
authors: Klebanov, Nikolai; Perez-Chada, Lourdes M.; Gupta, Sameer; Gottlieb, Alice B.; Merola, Joseph F.
title: Low gene expression of TNF, IL17A, IL23A, and IL12B in tumors: a safety surrogate to predict cancer survival associated with biologic therapies
date: 2020-08-18
journal: J Am Acad Dermatol
DOI: 10.1016/j.jaad.2020.08.050
sha: fb73bb354ccd0eb384511d03fd76e944bbc9f27a
doc_id: 860363
cord_uid: sp02scpa

nan

J o u r n a l P r e -p r o o f revolutionized psoriasis management, their safety in patients with active or recent malignancy 61 remains an area of unmet need. 1 We explored the relationship between low expression of key 62 genes encoding the respective targets of these biologic molecules, as a surrogate for targeted 63 biologic therapy, and overall survival across multiple cancers using data from The Cancer 64 Genome Atlas (TCGA). We retrieved clinical data and tumor RNA-Seq gene expression data for 65 31 malignancies. All patients had active cancer during sample collection. We used cox-66 proportional hazards to model overall survival as a function of low and high TNF, IL17A, IL23A, 67 and IL12B expression (split by median expression value). To mitigate the false discovery rate 68 (FDR) owing to multiple testing among distinct cancers, we applied a highly-conservative FDR 69 p-value correction to the results of the multivariate hazards models after adjusting for sex, age at 70 diagnosis, and pathologic tumor stage. 71

After removing cohorts that had relatively low (<10 th percentile) numbers of patients, 27 72 malignancies were evaluated (9274 patients, Table 1 ). In general, we found a reassuring pattern 73 of no impact on survival across multiple malignancies. Four potentially 'harmful' associations 74 were identified (Figure 1) 

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