Colorectal cancer-associated ~6kDa hyaluronan serves as a novel biomarker for cancer progression and metastasis.

Abstract

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 30kDa was markedly elevated in CRC tissues, and we defined HA with a MW of ~6kDa as CRC-associated LMW-HA. In line with this finding, ~6kDa HA was significantly accumulated in cancer tissues relative to total HA, and this LMW-HA played a critical role in tumor metastasis. Moreover, serum ~6kDa HA levels in CRC patients were significantly increased and positively correlated with the levels in matched cancer tissues. Elevated serum ~6kDa 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 ~6kDa HA levels were significantly reduced after tumor resection. Our study suggests that ~6kDa HA may serve as a new biomarker for estimating tumor progression, predicting LN metastasis, and monitoring tumor recurrence.