Linoleic acid pathway disturbance contributing to potential cancerization of intrahepatic bile duct stones into intrahepatic cholangiocarcinoma

BMC Gastroenterology

Jiongjiong Lu¹  Jiamei Yang¹  Xinjun Wang²  Shujun Sun³  Jun Li⁴  Haiying Sun⁴  Caifeng Liu⁴  Feng Xu⁴  Xingyang Zhong⁴  Shaodong Lv⁵  Junhua Lu⁵ 

[1] Department of Special Treatment, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University;Institute of Intestinal Diseases, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University;School of Biology and Food Engineering, Fuyang Normal University;The 1st Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University;The 5st Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University;

关键词: Intrahepatic cholangiocarcinoma;    Intrahepatic bile duct stone;    Linoleic acid;    Metabolomics;    GC–MS;   

DOI  :  10.1186/s12876-022-02354-2

来源: DOAJ

【 摘 要 】

Abstract Background Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy with poor prognosis. Intrahepatic bile duct stone (IBDS) is one of the key causes to ICC occurrence and can increase morbidity rate of ICC about forty times. However, the specific carcinogenesis of IBDS is still far from clarified. Insight into the metabolic phenotype difference between IBDS and ICC can provide potential mechanisms and therapeutic targets, which is expected to inhibit the carcinogenesis of IBDS and improve the prognosis of ICC. Methods A total of 34 participants including 25 ICC patients and 9 IBDS patients were recruited. Baseline information inclusive of liver function indicators, tumor biomarkers, surgery condition and constitution parameters etc. from patients were recorded. ICC and IBDS pathological tissues, as well as ICC para-carcinoma tissues, were collected for GC–MS based metabolomics experiments. Multivariate analysis was performed to find differentially expressed metabolites and differentially enriched metabolic pathways. Spearman correlation analysis was then used to construct correlation network between key metabolite and baseline information of patients. Results The IBDS tissue and para-carcinoma tissue have blurred metabolic phenotypic differences, but both of them essentially distinguished from carcinoma tissue of ICC. Metabolic differences between IBDS and ICC were enriched in linoleic acid metabolism pathway, and the level of 9,12-octadecadienoic acid in IBDS tissues was almost two times higher than in ICC pathological tissues. The correlation between 9,12-octadecadienoic acid level and baseline information of patients demonstrated that 9,12-octadecadienoic acid level in pathological tissue was negative correlation with gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) level in peripheral blood. These two indicators were all cancerization marker for hepatic carcinoma and disease characteristic of IBDS. Conclusion Long-term monitoring of metabolites from linoleic acid metabolism pathway and protein indicators of liver function in IBDS patients has important guiding significance for the monitoring of IBDS carcinogenesis. Meanwhile, further insight into the causal relationship between linoleic acid pathway disturbance and changes in liver function can provide important therapeutic targets for both IBDS and ICC.

【 授权许可】

Unknown