According to a study published in Nature Communications, a panel of 7 circulating microRNAs (miRNAs) capable of discriminating between malignant sarcomas and benign tumors or healthy controls with a high sensitivity and specificity was identified through comprehensive miRNA profiling of serum specimens from a large number of patients with bone or soft tissue sarcomas.
Bone and soft tissue sarcomas are a very rare and diverse group of cancers that are represented by over 50 histological subtypes; all are associated with a poor prognosis. Furthermore, there are many different types of soft tissue tumors; these can be classified as malignant (ie, sarcomas), intermediate (ie, those that are locally aggressive but rarely metastasize), and benign. At present, sarcomas can only be diagnosed through histopathologic examination, and are frequently diagnosed at a later stage; hence, a need exists for biomarkers of sarcoma to facilitate early detection.
In this study, comprehensive microarray analysis or quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis of miRNAs, small noncoding RNAs that function as posttranscriptional regulators of gene expression, was performed on 897 serum specimens from patients with bone and soft tissue tumors (414 patients with sarcomas; 144 patients with intermediate tumors; 339 patients with benign tumors) as part of a national project undertaken in Japan involving more than 10,000 serum specimens of patients with 13 different types of cancer.
Following distribution of the specimens from patients with sarcomas and benign soft tissue tumors into discovery, training, and validation sets, as well as the incorporation of specimens from healthy volunteers into the training and validation sets, a panel of 7 serum miRNAs (called Index VI and including miR-4736, miR-6836-3p, miR-4281, miR-762, miR-658, miR-4649-5p, and miR-4665-3p) was found that was able to identify sarcoma with a sensitivity of 0.96 (95% CI, 0.92–0.99), and a specificity of 0.95 (95% CI, 0.92–0.97).
Interestingly, Index VI was not found to be affected by histological subtype, primary site, or tumor stage/burden. Furthermore, there was no correlation between miRNA profiles in matched tumor and serum specimens.
“Together, these observations suggest that, unlike tumor-released conventional biomarkers, these miRNA biomarkers are not secreted from tumors,” the study authors commented. Rather, the authors hypothesized that “the serum levels of the 7-component miRNAs reflect the reactivity change induced by cancer-associated conditions in the different tumor types.”
In addition, Index VI values for serum specimens of patients with intermediate soft tissue tumors that were combined in an exploratory set with specimens from patients with benign soft tissue tumors and sarcomas were similar to those observed for sarcomas or benign soft tissue tumors “suggesting that serum miRNA profiles might reflect the premalignant potential of these [intermediate] subtypes.”
In conclusion, because the study authors had limited availability of serum samples across histological subtypes — a limitation they acknowledged — they proposed that “for the time being, Index VI
should be restricted to the differential diagnosis of benign and malignant bone and soft tissue tumors, and/or differential diagnosis of sarcoma and other cancers.”
- Asano N, Matsuzaki J, Ichikawa M, et al. A serum microRNA classifier for the diagnosis of sarcomas of various histological subtypes. Nat Commun. 2019;10(1):1299.