Simonsen Kira, Rode Anthony, Nicoll Amanda, Villadsen Gerda, Espelund Ulrick, Lim Lucy, Angus Peter, Arachchi Niranjan, Vilstrup Hendrik, Nexo Ebba, Grønbæk Henning
Department of Medicine V, Aarhus University Hospital , Aarhus , Denmark.
Scand J Gastroenterol. 2014 Sep;49(9):1096-102. doi: 10.3109/00365521.2014.921325. Epub 2014 Jun 24.
The vitamin B12 (B12)-binding protein haptocorrin (HC) has proven to be a potentially useful biomarker in patients with fibrolamellar hepatocellular carcinoma (HCC). Little is known concerning the level of HC and other B12-related proteins in patients with HCC as compared to patients with other chronic liver diseases (CLDs) and healthy controls. We hypothesized that HC could be a biomarker of HCC.
To investigate levels of HC and B12-related proteins in HCC compared to CLDs and healthy controls.
We investigated two patient populations: A cross-sectional cohort of HCC patients (n = 130), CLD patients (n = 102) and healthy controls (n = 46) and a cohort of 38 HCC patients studied at baseline and 1, 4, and 12 weeks following ablative treatment. Patients were evaluated by standard biochemistry, Child-Pugh-score and Barcelona Clinic Liver Cancer (BCLC) classification. We analyzed total B12 by routine methods and HC, transcobalamin (TC), B12 saturated TC (holoTC), and the soluble cell surface receptor for holoTC (sCD320) by in-house enzyme-linked immunosorbent assay.
HC showed higher median (range) levels for both HCC (590 [290-5860]) and CLD patients (620 [310-4010]) compared to controls (460 [250-2020]) (p < 0.01). Total B12, TC, holoTC, and sCD320 showed elevated levels in both HCC and CLD compared to controls. Only holoTC changed following treatment, without a concurrent change in TC.
B12 and B12-related proteins (total B12, HC, TC, holoTC, and sCD320) show elevations in both HCC and CLD patients compared to controls, suggesting a relation to CLD in general rather than to primary liver cancer. Thus, HC is not useful as a biomarker for HCC.
维生素B12（B12）结合蛋白运钴胺素（HC）已被证明是纤维板层型肝细胞癌（HCC）患者潜在有用的生物标志物。与其他慢性肝病（CLD）患者和健康对照相比，HCC患者体内HC及其他B12相关蛋白的水平情况鲜为人知。我们推测HC可能是HCC的生物标志物。
研究与CLD患者和健康对照相比，HCC患者体内HC及B12相关蛋白的水平。
我们调查了两组患者：一组为横断面队列，包括HCC患者（n = 130）、CLD患者（n = 102）和健康对照（n = 46）；另一组为38例HCC患者队列，在基线时以及消融治疗后1周、4周和12周进行研究。通过标准生化检查、Child-Pugh评分和巴塞罗那临床肝癌（BCLC）分类对患者进行评估。我们采用常规方法分析总B12，并通过内部酶联免疫吸附测定法分析HC、转钴胺素（TC）、B12饱和转钴胺素（全转钴胺素，holoTC）以及全转钴胺素的可溶性细胞表面受体（sCD320）。
与对照组（460 [250 - 2020]）相比，HCC患者（590 [290 - 5860]）和CLD患者（620 [310 - 4010]）的HC中位数（范围）水平更高（p < 0.01）。与对照组相比，HCC和CLD患者的总B12、TC、holoTC和sCD320水平均升高。仅holoTC在治疗后发生变化，而TC未同时发生变化。
与对照组相比，HCC和CLD患者体内的B12及B12相关蛋白（总B12、HC、TC、holoTC和sCD320）水平均升高，这表明其一般与CLD有关，而非与原发性肝癌有关。因此，HC并非HCC有用的生物标志物。
