Circulating microRNAs Capture Inflammatory and Muscle Wasting Phenotypes in Patients with Gastrointestinal Cancer
4 affiliations
- 1Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy
- 2Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, 00185 Rome, Italy
- 3Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, 00185 Rome, Italy
- 4Department of Interdisciplinary Studies on WellBeing, Health and Environmental Sustainability (BeSSA), Sapienza University of Rome, 00185 Rome, Italy
Abstract
Background: Cancer cachexia (CC) is a multifactorial syndrome marked by systemic inflammation and skeletal muscle (SM) wasting. Circulating microRNAs (miRNAs) may regulate tumor–host interactions. This study investigated whether circulating miRNAs are associated with inflammatory cytokines, CC, and CT-derived SM mass in treatment-naïve patients with gastrointestinal cancer. Methods: Fifty-four newly diagnosed patients with gastrointestinal cancer and 15 controls were studied. CC was defined according to Fearon criteria. SM mass was assessed using the CT-derived L3 SM index. Plasma levels of miR-15b, -21, -29a, -29b, -133a, -206, and -486 were quantified by RT-qPCR. Serum concentrations of IL-6, IL-8, IL-10, and TNF-α were measured with a multiplex assay. Results: Compared to controls, patients had higher miR-15b (p = 0.003), miR-21 (p < 0.001), and miR-29b (p < 0.001), whereas miR-133a (p = 0.007), miR-206 (p = 0.022), and miR-486 (p = 0.001) were lower. Serum IL-6, IL-8, IL-10, and TNF-α were all elevated in patients vs controls (all p < 0.001). miR-29b was higher in cachectic vs non-cachectic patients (p = 0.003) and remained independently associated with CC (p = 0.007; OR = 10.926; 95% CI: 1.933–61.756). miR-133a was reduced in patients with low SM mass vs. controls (p = 0.007). miR-29b was higher in patients with low SM mass and CC vs. those with high SM mass without CC (p = 0.026). miR-133a (p = 0.004) and miR-206 (p = 0.002) were reduced in patients with low SM mass and CC vs. controls. Conclusions: Circulating miRNAs showed distinct associations with systemic inflammation, CC, and SM status in treatment-naïve gastrointestinal cancer. These findings support the concept that miRNA alterations reflect distinct biological dimensions of tumor–host interactions and warrant validation in larger longitudinal studies.
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BibTeX
@article{tambaro2026circulating,
title = {{Circulating microRNAs Capture Inflammatory and Muscle Wasting Phenotypes in Patients with Gastrointestinal Cancer}},
author = {Federica Tambaro and Simona Orlando and Giovanni Imbimbo and Carmen Gallicchio and Veronica Rizzo and Elena Belloni and Giuseppe Nigri and Alessio Molfino and Maurizio Muscaritoli},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18213509},
url = {https://www.mdpi.com/2072-6694/18/21/3509},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Circulating microRNAs Capture Inflammatory and Muscle Wasting Phenotypes in Patients with Gastrointestinal Cancer
AU - Federica Tambaro
AU - Simona Orlando
AU - Giovanni Imbimbo
AU - Carmen Gallicchio
AU - Veronica Rizzo
AU - Elena Belloni
AU - Giuseppe Nigri
AU - Alessio Molfino
AU - Maurizio Muscaritoli
PY - 2026
DA - 2026/10/31
JO - Cancers
DO - 10.3390/cancers18213509
UR - https://www.mdpi.com/2072-6694/18/21/3509
AB - Background: Cancer cachexia (CC) is a multifactorial syndrome marked by systemic inflammation and skeletal muscle (SM) wasting. Circulating microRNAs (miRNAs) may regulate tumor–host interactions. This study investigated whether circulating miRNAs are associated with inflammatory cytokines, CC, and CT-derived SM mass in treatment-naïve patients with gastrointestinal cancer. Methods: Fifty-four newly diagnosed patients with gastrointestinal cancer and 15 controls were studied. CC was defined according to Fearon criteria. SM mass was assessed using the CT-derived L3 SM index. Plasma levels of miR-15b, -21, -29a, -29b, -133a, -206, and -486 were quantified by RT-qPCR. Serum concentrations of IL-6, IL-8, IL-10, and TNF-α were measured with a multiplex assay. Results: Compared to controls, patients had higher miR-15b (p = 0.003), miR-21 (p < 0.001), and miR-29b (p < 0.001), whereas miR-133a (p = 0.007), miR-206 (p = 0.022), and miR-486 (p = 0.001) were lower. Serum IL-6, IL-8, IL-10, and TNF-α were all elevated in patients vs controls (all p < 0.001). miR-29b was higher in cachectic vs non-cachectic patients (p = 0.003) and remained independently associated with CC (p = 0.007; OR = 10.926; 95% CI: 1.933–61.756). miR-133a was reduced in patients with low SM mass vs. controls (p = 0.007). miR-29b was higher in patients with low SM mass and CC vs. those with high SM mass without CC (p = 0.026). miR-133a (p = 0.004) and miR-206 (p = 0.002) were reduced in patients with low SM mass and CC vs. controls. Conclusions: Circulating miRNAs showed distinct associations with systemic inflammation, CC, and SM status in treatment-naïve gastrointestinal cancer. These findings support the concept that miRNA alterations reflect distinct biological dimensions of tumor–host interactions and warrant validation in larger longitudinal studies.
SN - 2072-6694
ER -