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. 2023 Jul 4;24:374. doi: 10.1186/s12864-023-09462-7

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 9 — Summary figure. Females and males display different timelines in the transcriptional response to tumor development and cancer cachexia. Females display an early dysregulation in extracellular matrix remodeling and cellular structure-associated pathways followed by an increase in JAK-STAT pathways-associated gene expression. Interestingly, besides the maintenance of gastrocnemius muscle mass, downregulation of interferon type II genes is unique to females through cancer cachexia development. Delayed transcriptomic changes in mitochondrial pathways match functional mitochondrial impairments previously reported. Males show upregulation inflammation pathways, and interferon signaling genes at pre-cachectic and cachectic states. Additionally, males show early disruption in mitochondrial function that precedes the loss of gastrocnemius mass and major transcriptomic changes in mitochondrial genes. Invert expression profiling of interferon-associated genes between biological sexes represents a transcriptomic signature to each biological sex in response to cancer cachexia development and suggests a potential target for muscle loss during cancer-induced cachexia. Created with BioRender.com