Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma

Chaisaingmongkol, Jittiporn; Budhu, Anuradha; Dang, Hien; Rabibhadana, Siritida; Pupacdi, Benjarath; Kwon, So Mee; Forgues, Marshonna; Pomyen, Yotsawat; Bhudhisawasdi, Vajarabhongsa; Lertprasertsuke, Nirush; Chotirosniramit, Anon; Pairojkul, Chawalit; Auewarakul, Chirayu; Sricharunrat, Thaniya; Phornphutkul, Kannika; Sangrajrang, Suleeporn; Cam, Maggie; He, Ping; Hewitt, Stephen M.; Ylaya, Kris; Wu, Xiaolin; Andersen, Jesper B.; Thorgeirsson, Snorri S.; Waterfall, Joshua J.; Zhu, Yuelin J.; Walling, Jennifer; Stevenson, Holly; Edelman, Daniel C.; Meltzer, Paul S.; Loffredo, Christopher A.; Hama, Natsuko; Shibata, Tatsuhiro; Wiltrout, Robert H.; Harris, Curtis C.; Mahidol, Chulabhorn; Ruchirawat, Mathuros; Wang, Xin Wei

doi:10.1016/j.ccell.2017.05.009

Cited by 341 publications

(349 citation statements)

References 59 publications

Supporting

Mentioning

328

Contrasting

Unclassified

Order By: Relevance

“…This technique allowed different metabolomics subtypes of NASH to be identified in animal models and patients . Moreover, integration of genomics, transcriptomics, and metabolomics in tumor tissue has been proposed for the identification of molecular subtypes of HCC and iCCA with similar prognosis . Our metabolomic study was conducted on serum searching for biomarkers that can differentially diagnose iCCA from HCC, the most frequent type of liver cancer, as well as for PSC, a condition with an enhanced risk of developing iCCA.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Arguably the greatest obstacle in the development of therapeutic strategies for CCA is its extensive molecular heterogeneity, further confounded by mixed patient cohorts of varied clinical and pathological features. Previous efforts have identified individual genomic events responsible for specific therapeutic sensitivities (e.g., IDH mutations and FGFR2 fusions) and broad clusters of patients with diverse characteristic pathobiological properties . What remains unclear are the broader network implications of such individual events and the molecular origins of these clusters.…”

Section: Discussionmentioning

confidence: 99%

Genomic perturbations reveal distinct regulatory networks in intrahepatic cholangiocarcinoma

et al. 2018

Self Cite

View full text Add to dashboard Cite

Stratification of intrahepatic cholangiocarcinoma patients based on occurrence of mutations in three classifier genes (IDH, KRAS, TP53) revealed unique oncogenic programs (mutational, structural, epimutational) that influence pharmacologic response in drug repositioning protocols; this genome dissection approach highlights the potential of individual mutations to induce extensive molecular heterogeneity and could facilitate advancement of therapeutic response in this dismal disease. (Hepatology 2018).

show abstract

“…As one of the most common life-threatening malignancies worldwide, hepatocellular carcinoma (HCC) was estimated to cause 748, 300 new liver cancer cases and 695, 900 cancer deaths worldwide per year and nearly half of these cases and deaths were estimated to take place in China [1-3]. Although the major risk factors have been identified, including hepatitis C (HCV) and B virus (HBV) infection, toxins (aflatoxin B1), chronic alcohol abuse and nonalcoholic fatty liver disease [4-6].…”

Section: Introductionmentioning

confidence: 99%

Circulating LncRNAs Serve as Diagnostic Markers for Hepatocellular Carcinoma

Yuan¹,

Sun²,

Liu³

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Circulating (serous or plasmic) long non-coding RNA (lncRNA) as biomarkers for predicting the diagnosis or prognosis of human disease have been well documented. Due to the sensibility or specificity limitation of Alpha Fetoprotein (AFP), a cluster lncRNAs were revealed as fingerprints for hepatocellular carcinoma (HCC). In this study, we enrolled all the reported circulating lncRNAs in HCC as candidate targets and examined in an independent cohort. Methods: The candidate lncRNAs were determined by qRT-PCR divided into training and validation sets. The risk score analysis was employed to evaluate the potential diagnosis ability of the lncRNAs independently or combining with AFP value. The receiver operating characteristic curve (ROC) was applied for presentation of sensibility or specificity. Results: Among the ten candidate circulating lncRNA, LINC00152, RP11-160H22.5, XLOC014172 and LOC149086 were screened with significant difference in training set. Further investigation in validation set indicated LINC00152, RP11-160H22.5 and XLOC014172 might be the fingerprints for HCC comparing with chronic hepatitis (CH) patients or healthy controls. The risk score analysis revealed the combination of three lncRNAs with AFP could distinguish the HCC from either CH or healthy control with the area under curve value (AUC) of 0.986 and 0.985, respectively. Conclusion: The three lncRNAs may act as novel biomarkers for acting as fingerprint in HCC combining with AFP.

show abstract

Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma

Cited by 341 publications

References 59 publications

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

Genomic perturbations reveal distinct regulatory networks in intrahepatic cholangiocarcinoma

Circulating LncRNAs Serve as Diagnostic Markers for Hepatocellular Carcinoma

Contact Info

Product

Resources

About