Liquid Biopsy for Cancer Cachexia: Focus on Muscle-Derived microRNAs

Abstract

Cancer cachexia displays a complex nature in which systemic inflammation, impaired energy metabolism, loss of muscle and adipose tissues result in unintentional body weight loss. Cachectic patients have a poor prognosis and the presence of cachexia reduces the tolerability of chemo/radio-therapy treatments and it is frequently the primary cause of death in advanced cancer patients. Early detection of this condition could make treatments more effective. However, early diagnostic biomarkers of cachexia are currently lacking. In recent years, although solid biopsy still remains the “gold standard” for diagnosis of cancer, liquid biopsy is gaining increasing interest as a source of easily accessible potential biomarkers. Moreover, the growing interest in circulating microRNAs (miRNAs), has made these molecules attractive for the diagnosis of several diseases, including cancer. Some muscle-derived circulating miRNA might play a pivotal role in the onset/progression of cancer cachexia. This topic is of great interest since circulating miRNAs might be easily detectable by means of liquid biopsies and might allow an early diagnosis of this syndrome. We here summarize the current knowledge on circulating muscular miRNAs involved in muscle atrophy, since they might represent easily accessible and promising biomarkers of cachexia.

Small non‐coding RNA profiling in patients with gastrointestinal cancer

“…Selected circulating miRNAs (miR‐15b‐5p, miR‐21‐5p, miR‐29a‐3p, and miR‐29b‐3p, miR‐133a‐3p, miR‐206 and miR‐486‐5p) were assessed in 24 out of 25 cancer patients and in 14 out of 15 controls after the exclusion of one blood sample for each group due to specimen deterioration. The selection was based on previous reports involving those miRNAs in muscle homeostasis 10 . In particular, miR‐133a‐3p, miR‐206 and miR‐486‐5p belong to muscle‐specific miRNAs (myomiRs) 13 .…”

“…They are involved in several events such as cell proliferation, differentiation and death, DNA repair and oxidative stress response 9 . MiRNAs have been shown to be stable and able of circulating in blood, either in extracellular vesicles (EVs) or protein‐bound, 10 explaining their ability to act also distally from the site of production and release 11,12 . Some miRNAs, also named myomiR, are enriched in the skeletal muscle, and their involvement in the pathogenesis of muscle wasting during cancer has been hypothesized 13,14 .…”

MicroRNAs: Novel players in the diagnosis and treatment of cancer cachexia (Review)

“…Thus, the diagnostic value of miRNAs for cancer cachexia should be restricted to circulating miRNAs. miRNAs with high stability in body fluids can be potentially used as non-invasive markers (98,99). miRNAs from plasma/serum have been reported as biomarkers for the early diagnosis of different types of tumor, including gastric cancer (100), BC (101) and pancreatic cancer (102).…”

Extracellular vesicles in cancer cachexia: deciphering pathogenic roles and exploring therapeutic horizons

“…The expression profiles of muscle-secreted miRNAs have been extensively studied, revealing their significant role in regulating muscle metabolism during CC [ 33 , 145 , 188 ]. Muscle-specific miRNAs, including miR-1, miR-133a, miR-133b, miR-206, miR-208a, miR-208b, and miR-499, along with muscle-enriched miR-486, are known to influence myogenesis, proliferation, differentiation, apoptosis of myotubes, and protein synthesis in skeletal muscle of CC patients [ 189 , 190 ]. Recent research demonstrates that exosomes from skeletal muscle, containing myomiRs such as miR-1, miR-133a, miR-133b, and miR-206, play a dual role: they enter the circulatory system and facilitate inter-tissue communication between muscles, offering insights into new therapeutic approaches for muscle function [ 190 ].…”