Ever since the “seed-and-soil” hypothesis, the mechanism of cancer metastatic organotropism is still an unsolved mystery. In colorectal cancer (CRC), there is still no robust metastasis predictive biomarkers for distant organ metastasis, which is the most common cause of deaths. In spite of the function of exosome in RNA and protein delivery, its clinical significance in CRC metastasis remains uncertain. Here, we evaluated the potential role of serum exosome integrin in CRC metastasis.
Tissue integrin αvβ5 was quantified by quantitative reverse-transcription PCR in 31 pairs of primary CRC and corresponding matched liver metastasis (LM), with non-LM as control. Serum exosomal integrin αvβ5 was accessed by ELISA in 126 CRC patients with LM and 166 CRC patients without, as well as when LM was diagnosed in these 166 patients in exploratory cohort. In prospective validation cohort, serum exosomal integrin αvβ5 was investigated in 135 initially diagnosed CRC patients without metastasis. CRC-associated metastasis mouse models were established to verify the role of serum exosomal integrin αvβ5.
Integrin αvβ5 level in LM was significantly increased compared with that in non-LM, which was correlated with its expression in primary CRC. Serum exosomal integrin αvβ5 was significantly increased in CRC patients with LM than those without, in a TNM stage-dependent manner. Moreover, it was found that serum exosomal integrin αvβ5 in CRC patients was significantly upregulated when LM occurred and associated with unfavorable survival. In validation cohort, increased serum exosomal integrin αvβ5 indicated higher risk of LM and unfavorable prognosis. Serum exosomal integrin αvβ5 was significantly increased in mice with LM compared with controls.
Our clinical and animal model data indicate that increased levels of serum integrin αvβ5 associate with CRC LM and unfavorable survival. These results suggested that circulating integrin αvβ5 could be a promising non-invasive predictor for CRC LM and prognosis.
Clinical trial identification
Legal entity responsible for the study
Xi'an Jiaotong University.
All authors have declared no conflicts of interest.