Increased level of circulating U2 small nuclear RNA fragments indicates metastasis in melanoma patients.
Background: Melanoma is the most aggressive skin cancer and, despite recent advances in therapy, about 20% of the patients die of their disease. Early relapse detection and monitoring of therapy response are crucial for efficient treatment of advanced melanoma. Thus, there is a need for blood-based biomarkers in melanoma management. Serum-derived U2 small nuclear RNA fragments (RNU2-1f) were previously shown to be blood-based biomarkers for gastrointestinal and gynecologic malignancies. Here we examined whether RNU2-1f may also serve as diagnostic biomarker in advanced melanoma.


METHODS
Circulating RNU2-1f levels were quantified by comparative reverse transcription PCR in a training cohort of patients with metastatic melanoma (n=33, thereof regionally metastasized to skin and lymph nodes, n=23, and distantly metastasized, n=10) vs. patients with benign naevi (n=16) vs. healthy controls (n=39). RESULTS were validated in an independent patient cohort with distant metastasis (n=16) vs. controls (n=18).


RESULTS
Circulating RNU2-1f levels in the training cohort were significantly increased in serum of regionally and distantly metastatic patients, compared with patients with benign naevi or healthy controls (p<0.0001) and allowed accurate detection of regional (AUC 0.80) as well as distant (AUC 0.84) metastasis. In the validation cohort, increased RNU2-1f levels were confirmed and enabled highly specific detection of distant metastasis (sensitivity 81%, specificity 100%, AUC 0.94).


CONCLUSIONS
This is the first report to suggest a blood-based snRNA serving as a diagnostic biomarker for melanoma metastasis. Our data provide a rationale for further defining clinical utility of circulating RNU2-1f in metastasis detection in the management of melanoma patients at risk of relapse and/or with advanced disease.
Jan Dominik
JD
Kuhlmann
Pauline
P
Wimberger
Katja
K
Wilsch
Michael
M
Fluck
Ludwig
L
Suter
Georg
G
Brunner
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000473:pathology*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012342:RNA, Small Nuclear / Q000097:blood*; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood; D012878:Skin Neoplasms / Q000097:blood* / Q000473:pathology*; D055815:Young Adult
D015415:Biomarkers; D012342:RNA, Small Nuclear; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; C405484:U2 small nuclear RNA; D007770:L-Lactate Dehydrogenase