Circulating MicroRNAs Reflect Systemic Inflammation and Metabolic Dysfunction in Oesophageal Squamous Cell Carcinoma-Associated Cachexia.

BACKGROUND

Cachexia in oesophageal squamous cell carcinoma is driven by systemic inflammation and malnutrition and is associated with poor survival. We evaluated whether circulating miRNAs can identify ESCC cachexia and reflect its inflammatory-nutritional phenotype.

METHODS

We enrolled 126 participants: 42 healthy controls and 84 treatment-naïve patients with ESCC, equally classified as noncachectic or cachectic using international consensus criteria. Small-RNA sequencing in a discovery subset (n = 4/group) was followed by cohort-wide qRT-PCR. Exploratory within-cohort discrimination was assessed by receiver operating characteristic (ROC) analysis; survival associations were evaluated using Kaplan-Meier and univariate Cox analyses.

RESULTS

Cachectic ESCC was characterized by lower albumin, total protein and prealbumin and higher IL-6, TNF-α, CRP and IL-1β than noncachectic ESCC (all p < 0.05). Circulating hsa-miR-5187-5p and hsa-miR-4433b-3p increased stepwise from controls to noncachectic and cachectic ESCC. For noncachectic versus cachectic ESCC, AUCs were 0.8594 and 0.8175, respectively (both p < 0.0001); for controls versus cachectic ESCC, AUCs were 0.9439 and 0.8889. Cachexia was associated with shorter overall survival (HR 1.708, 95% CI 1.011-2.887; p = 0.026), as were high miR-5187-5p (HR 3.635) and miR-4433b-3p (HR 3.190) expression. Correlations with inflammatory markers and albumin were weak to moderate.

CONCLUSIONS

hsa-miR-5187-5p and hsa-miR-4433b-3p are candidate circulating indicators of ESCC-associated cachexia and its inflammatory-metabolic milieu. Their discriminatory and prognostic performance remains exploratory because analyses were conducted within the same cohort and were not comprehensively adjusted for tumour stage or other clinicopathological factors.