Colorectal cancer-associated similar to 6 kDa hyaluronan serves as a novel biomarker for cancer progression and metastasis
Colorectal cancer-associated similar to 6 kDa hyaluronan serves as a novel biomarker for cancer progression and metastasis
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与结直肠癌相关的类似于 6 kDa 透明质酸可作为癌症进展和转移的新型生物标志物
DOI：
10.1111/febs.14859
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发表时间：
2019
期刊：
影响因子：
5.4
通讯作者：
Gao Feng
中科院分区：
文献类型：
--
作者：
Zhang Guoliang;Lu Renquan;Wu Man;Liu Yiwen;He Yiqing;Xu Jing;Yang Cuixia;Du Yan;Gao Feng
低分子量透明质酸（LMW-HA）被认为在肿瘤中蓄积并发挥促肿瘤作用。本研究旨在鉴定结直肠癌（CRC）相关的LMW-HA，精确测定其MW，并阐明其在预测肿瘤进展中的作用。评估从CRC和配对的非癌组织提取的HA的MW分布。我们发现，分子量低于30 kDa的HA水平在CRC组织中显著升高，我们将分子量约为6 kDa的HA定义为CRC相关的LMW-HA。与这一发现一致，相对于总HA，约6 kDa HA在癌组织中显著积累，并且这种LMW-HA在肿瘤转移中起关键作用。此外，CRC患者的血清~ Δ 6 kDa HA水平显著升高，并与匹配的癌组织中的水平呈正相关。血清HA水平升高可用于区分结直肠癌患者和非结直肠癌患者，并与早期复发、晚期肿瘤淋巴结转移、淋巴管浸润和淋巴结（LN）转移相关。值得注意的是，肿瘤切除术后血清HA水平显著降低。我们的研究表明，~ 6 kDa HA可能作为一种新的生物标志物，用于估计肿瘤进展，预测LN转移，并监测肿瘤复发。
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 30ákDa was markedly elevated in CRC tissues, and we defined HA with a MW of ~á6ákDa as CRC‐associated LMW‐HA. In line with this finding, ~á6ákDa HA was significantly accumulated in cancer tissues relative to total HA, and this LMW‐HA played a critical role in tumor metastasis. Moreover, serum ~á6ákDa HA levels in CRC patients were significantly increased and positively correlated with the levels in matched cancer tissues. Elevated serum ~á6ákDa 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 ~á6ákDa HA levels were significantly reduced after tumor resection. Our study suggests that ~á6ákDa HA may serve as a new biomarker for estimating tumor progression, predicting LN metastasis, and monitoring tumor recurrence.