Serum Metabolites as Diagnostic Biomarkers for Cholangiocarcinoma, Hepatocellular Carcinoma, and Primary Sclerosing Cholangitis.

Serum Metabolites as Diagnostic Biomarkers for Cholangiocarcinoma, Hepatocellular Carcinoma, and Primary Sclerosing Cholangitis.
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DOI:
10.1002/hep.30319
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发表时间:
2019-08
期刊:
Hepatology (Baltimore, Md.)
影响因子:
--
通讯作者:
Macias RIR
Macias RIR
中科院分区:
其他
文献类型:
--
作者:
Banales JM;Iñarrairaegui M;Arbelaiz A;Milkiewicz P;Muntané J;Muñoz-Bellvis L;La Casta A;Gonzalez LM;Arretxe E;Alonso C;Martínez-Arranz I;Lapitz A;Santos-Laso A;Avila MA;Martínez-Chantar ML;Bujanda L;Marin JJG;Sangro B;Macias RIR

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肝内胆管细胞癌(iCCA)和肝细胞癌(HCC)的早期和鉴别诊断的非侵入性方法是目前的临床挑战。通过新的高通量技术分析低分子量代谢物是识别生物标志物的策略。在这里,我们研究了血清代谢组是否可以在iCCA和HCC的诊断中提供有用的生物标志物,并可以区分iCCA和HCC。由于原发性硬化性胆管炎(PSC)是CCA的危险因素,因此还比较了PSC和CCA的血清代谢谱。对iCCA、HCC和PSC患者和健康个体(n = 20/组)血清中脂质和氨基酸水平的分析显示出差异谱。几种代谢物对iCCA与对照、HCC与对照和PSC与对照显示出较高的诊断价值,接受者工作特征曲线下面积(AUC)大于血清中非特异性肿瘤标志物碳水化合物抗原19 - 9(CA 19 - 9)和甲胎蛋白(AFP)的AUC,这两种标志物通常分别用于帮助诊断iCCA和HCC。结合甘氨酸、天冬氨酸、SM(42:3)和SM(43:2)的算法的开发允许准确区分两种类型肿瘤的诊断(活检证实)。所提出的模型产生0.890 AUC,75%灵敏度和90%特异性。通过PC(34:3)和组氨酸的组合的另一算法准确地允许区分PSC与iCCA,AUC为0.990,100%灵敏度和70%特异性。这些结果在每组14 - 15例患者的独立队列中得到验证,并与非酒精性脂肪性肝病/非酒精性脂肪性肝炎患者的特征进行了比较。总结:某些代谢物的血清浓度的特定变化有助于区分iCCA与HCC或PSC,并有助于这些疾病的早期诊断。
Early and differential diagnosis of intrahepatic cholangiocarcinoma (iCCA) and hepatocellular carcinoma (HCC) by noninvasive methods represents a current clinical challenge. The analysis of low‐molecular‐weight metabolites by new high‐throughput techniques is a strategy for identifying biomarkers. Here, we have investigated whether serum metabolome can provide useful biomarkers in the diagnosis of iCCA and HCC and could discriminate iCCA from HCC. Because primary sclerosing cholangitis (PSC) is a risk factor for CCA, serum metabolic profiles of PSC and CCA have also been compared. The analysis of the levels of lipids and amino acids in the serum of patients with iCCA, HCC, and PSC and healthy individuals (n = 20/group) showed differential profiles. Several metabolites presented high diagnostic value for iCCA versus control, HCC versus control, and PSC versus control, with areas under the receiver operating characteristic curve (AUC) greater than those found in serum for the nonspecific tumor markers carbohydrate antigen 19‐9 (CA 19‐9) and alpha‐fetoprotein (AFP), commonly used to help in the diagnosis of iCCA and HCC, respectively. The development of an algorithm combining glycine, aspartic acid, SM(42:3), and SM(43:2) permitted to accurately differentiate in the diagnosis of both types of tumors (biopsy‐proven). The proposed model yielded 0.890 AUC, 75% sensitivity, and 90% specificity. Another algorithm by combination of PC(34:3) and histidine accurately permitted to differentiate PSC from iCCA, with an AUC of 0.990, 100% sensitivity, and 70% specificity. These results were validated in independent cohorts of 14‐15 patients per group and compared with profiles found in patients with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Conclusion: Specific changes in serum concentrations of certain metabolites are useful to differentiate iCCA from HCC or PSC, and could help in the early diagnosis of these diseases.
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