頭頸部癌におけるIL32 mRNA発現の亢進

Cancer-related sarcopenia (CRS) is a significant complication of head and neck carcinoma (HNC), characterised by muscle degeneration and poor clinical outcomes. Although various dietary and therapeutic interventions have been explored, most of them remain empirical, and the molecular mechanisms underlying CRS are not yet fully understood.

Transcription profiles of muscle fragments from 29 HNC patients and 8 control donors were analysed by bulk RNA sequencing (6/29 and 3/8) and/or RT-qPCR (29/29 and 5/8). In parallel, differentiating human myoblasts (AB1190) were subjected to indirect co-culture with two types of effector cells: HNC cells (FaDu) or control epithelial cells (NHEK). The contactless effects of effector cells on target myoblasts were investigated using cell imaging to assess muscular differentiation, RT-qPCR and Western blot to assess gene expression.

Bulk RNA sequencing identified 789 differentially expressed transcripts between HNC and control samples. Subsequent RT-qPCR analysis focused on IL32 and BIRC3 mRNAs (up-regulated in HNC samples) and ACE1 mRNA (down-regulated). Among male HNC patients, the IL32/ACE1 mRNA ratio was significantly elevated in CRS cases (p = 0.0001, effect size r = 0.57) and correlated with the severity of muscle atrophy (negative correlation with the Skeletal Muscle Index at a threshold of 10%: p = 0.093, r = -0.41). In contrast, no such trend was observed for the BIRC3/ACE1 ratio. Exposure of human myoblasts to HNC cells induced inhibition of myogenesis and strong up-regulation of IL32 mRNA and protein. In contrast, these effects were absent or much smaller under exposure to NHEK controls.

IL32 is a potential biomarker for CRS in HNC patients. In addition, the HNC-myoblast co-cultivation model provides a promising in vitro system to study CRS mechanisms, potentially reducing the reliance on animal models.