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Sensitive and specific detection of micrometastasis of hepatic carcinoma in peripheral blood by immunomagnetic nanobeads polymerase chain reaction

This study aims to determine the value of miR-133a-3p in diagnosing micrometastasis of hepatic carcinoma (HCC) from peripheral blood (PB) samples and dissecting the molecular mechanism (MM) of micrometastasis. We selected 70 patients with micrometastasis of HCC from our hospital between
 August 2014 to August 2020 for the research (Res) group and enrolled 55 patients with HCC but without micrometastasis in the control (Con) group. We collected PB samples from each participant and quantified miR-133a-3p in each sample using immunomagnetic nanobeads (IMNBs)-based PCR and RT-PCR.
 In contrast to the Con group, the Res group presented a significant down-regulation of miR-133a-3p in PB. The IMNBs and RT-PCR showed that miR-133a-3p exhibited the area under the curves (AUCs) of 0.882 and 0.845, specificities of 81.82% and 74.55%, and sensitivities of 85.71% and 88.57%,
 respectively. Due to its higher specificity and sensitivity, IMNBs were utilized. IMNBs were then used to quantify miR-133a-3p in HCC cells. Additionally, we explored the association of miR-133a-3p with PAF; miR-133a-3p was inversely correlated with AFP (r =−0.614; P <0.001).
 miR-133a-3p’s targeting association with MMP15 and the corresponding MM was verified and analyzed. The up-regulation of miR-133a-3p levels inhibited the migration and invasion of HCC cells, while its down-regulation yielded the opposite effect. Moreover, miR-133a-3p negatively regulated
 the protein level of MMP15, the migration and invasion capacity of HCC cells was greatly impacted. In short, miR-133a-3p decreased in HCC micrometastasis. The detection of miR-133a-3p by IMNBs is both specific and sensitive in diagnosing the micrometastasis. miR-133a-3p is of enormous value
 in diagnosing HCC micrometastasis from PB samples, and its up-regulation can inhibit MMP15 and hinder HCC metastasis.