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.
Sarcopenia has emerged as a significant predictor of adverse outcomes in cancer. Specifically, this is also true for patients with bladder cancer undergoing radical cystectomy (RC). This retrospective study investigates the roles of the biomarkers interleukin-6 (IL-6) and growth differentiation factor-15 (GDF-15), in the context of sarcopenia, assessing their impact on oncological and survival outcomes.
Preoperative serum IL-6 and GDF-15 levels were analysed in 179 patients undergoing RC. Their association with sarcopenia, adverse pathological features and survival outcomes was investigated.
Elevated IL-6 and GDF-15 levels were significantly correlated with the presence of sarcopenia (p = 0.04 and p = 0.03, respectively). IL-6 and GDF-15 levels in serum showed a positive correlation (Spearman r = 0.45, 95%CI 0.32–0.56, p < 0.01). Higher IL-6 and GDF-15 levels were also associated with higher tumour stages (both p < 0.01), positive lymph nodes (p = 0.02 and p < 0.01) and unfavourable surgical margins (both p < 0.01). Patients with both sarcopenia and high IL-6 or GDF-15 levels exhibited significantly worse overall survival and cancer-specific survival in multivariate Cox regression analysis.
These findings highlight the interplay between IL-6, GDF-15, sarcopenia and tumour progression, suggesting that IL-6 and GDF-15 may serve as valuable prognostic biomarkers and potential therapeutic targets. Further research is warranted to explore targeted therapeutic strategies aimed at mitigating sarcopenia and systemic inflammation in this patient population.
Aromatase inhibitors (AIs) significantly increase the risk of osteoporosis and related fractures in postmenopausal women with hormone receptor (HR)–positive early breast cancer (EBC), posing a substantial clinical and economic burden. Effective fracture prevention strategies are critical, especially in resource-constrained settings such as China.
A Markov microsimulation model was developed to evaluate the cost-effectiveness of fracture prevention strategies for 60-year-old postmenopausal women with HR-positive EBC treated with AIs in China. Six strategies were compared: (a) no intervention, (b) one-time bone mineral density (BMD) screening followed by anti-osteoporotic medication for patients with osteoporosis or osteopenia, (c) annual BMD screening followed by anti-osteoporotic medication for patients with osteoporosis or osteopenia and (d) universal anti-osteoporotic medication without prior BMD screening. Outcomes included incremental cost-effectiveness ratios (ICERs) per quality-adjusted life-year (QALY) gained versus China's willingness-to-pay (WTP) threshold (3 × GDP/capita = $38 223/QALY).
All interventions reduced fractures but increased costs versus no intervention. For women aged 60–64 years, one-time BMD screening followed by therapy for osteoporosis (T-score ≤ −2.5) achieved an ICER of $17 368/QALY, below the WTP threshold. Annual screening yielded marginally higher QALYs (+0.0096) but higher costs (+$895.09), resulting in an ICER exceeding $38 223/QALY. For women ≥ 65 years, both one-time screening for osteoporosis or osteopenia and universal therapy were cost-effective. Universal therapy dominated in high-risk subgroups (history of falls/fractures), achieving the highest QALY gains.
One-time BMD screening with selective alendronate for osteoporosis is cost-effective for Chinese women aged ≥ 60 receiving AIs, aligning with China's healthcare constraints. Universal therapy becomes favourable for older or high-risk subgroups. These data-driven findings support tailored strategies to optimise bone health management and resource allocation.
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