Low molecular weight hyaluronan (LMW-HA) is believed to accumulate in tumors and to exert protumor effects. This study aimed to identify colorectal cancer (CRC)-associated LMW-HA, precisely determine its MW, and elucidate its role in predicting tumor progression. The MW distribution of HA extracted from CRC and paired noncancerous tissues was evaluated. We found that the level of HA with a MW below 30 kDa was markedly elevated in CRC tissues, and we defined HA with a MW of ~ 6 kDa as CRC-associated LMW-HA. In line with this finding, ~ 6 kDa HA was significantly accumulated in cancer tissues relative to total HA, and this LMW-HA played a critical role in tumor metastasis. Moreover, serum ~ 6 kDa HA levels in CRC patients were significantly increased and positively correlated with the levels in matched cancer tissues. Elevated serum ~ 6 kDa HA levels could be used to discriminate patients with or without CRC and was associated with early relapse, advanced tumor-node-metastasis stage, lymphovascular invasion, and lymph node (LN) metastasis. Notably, serum ~ 6 kDa HA levels were significantly reduced after tumor resection. Our study suggests that ~ 6 kDa HA may serve as a new biomarker for estimating tumor progression, predicting LN metastasis, and monitoring tumor recurrence.
Keywords: biomarker; colorectal cancer; hyaluronan; metastasis.
© 2019 Federation of European Biochemical Societies.