10-gene, RNA-based signature detects circulating tumour cells from HCC
A novel, multi-gene, RNA-based molecular signature can detect circulating tumour cells (CTCs) from hepatocellular carcinomas (HCCs) with high specificity and sensitivity, a new study claims.
A CTC-iChip microfluidic device was used to efficiently separate, and thus enrich, CTCs from hematopoietic cells from blood samples. RNA from the CTCs were extracted, amplified through digital PCR and compared against various pre-existing lists of gene transcripts, yielding a 10-gene signature to potentially identify CTCs from HCC.
This gene signature was tested against 26 healthy controls, 31 patients with chronic liver disease (CLD), 16 untreated HCC patients, 32 HCC patients receiving therapy, 15 HCC patients who had undergone curative interventions and have no evidence of the disease, and 44 patients with other malignancies.
The 10 genes identified were transferrin, retinol binding protein 4, glypican 3, fibrinogen gamma chain, fibrinogen beta chain, fatty acid binding protein 1, apolipoprotein H, albumin, alpha 2-HS glycoprotein and alphafetoprotein.
Of the patients with untreated HCC, 9 (56 percent) tested positive when evaluated using the gene signature. In contrast, only 1 patient (3 percent) with non-malignant CLDs and 2 controls (7.6 percent) tested positive (p<0.0001).
Similarly, only 1 patient (7 percent) with no evidence of the disease following curative interventions tested positive (p=0.56), indicating that the signature can identify patients with an active disease.
Furthermore, 6 of the 10 genes identified were able to distinguish between HCC and other malignancies. In fact, in patients with non-HCC malignancies, 39 cases (88 percent) were correctly differentiated from HCC at a sensitivity of 50 percent.
Broadly, the current study outlines a platform for detecting CTCs. Further developments can, in turn, apply this platform to other cancers.