Research progress of bile biomarkers and their immunoregulatory role in biliary tract cancers

Li, Yuncheng; Li, Kang-shuai; Liu, Zengli; Tang, Yong-chang; Hu, Xiaoping; Li, Xing-yong; Shi, Anda; Zhao, Li-ming; Shu, Lizhuang; Lian, Shuo; Yan, Zhang-di; Huang, Shao Mei; Sheng, Guo-li; Song, Yan; Liu, Yun-jia; Fan, Huiying; Zhang, Minghui; Zhang, Zongli

doi:10.3389/fimmu.2022.1049812

Cited by 7 publications

(11 citation statements)

References 133 publications

(151 reference statements)

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“…In routine blood test, we found that CCA patients had signi cantly higher serum levels of TBIL, ALT, AST, TBA, CA19-9, and CEA than those of gallstone patients, which is consistent with previous reports [12].…”

Section: Discussionsupporting

confidence: 92%

“…Yun Cheng Li et al summarized the potential diagnostic value of bile markers in biliary tract tumors. Among them, the AUC of Vascular Endothelial Growth Factor levels was as high as 0.93 [12]. In addition, with the continuous development of omics technology, people have used a large amount of genetics, epigenetics, proteomics, and metabolomics to further better identify CCA features.…”

Section: Discussionmentioning

confidence: 99%

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Bile-derived cfDNA of syncytin-1 and SLC7A11 as a potential molecular marker for early diagnosis of cholangiocarcinoma

He,

Qian,

et al. 2024

Preprint

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Background: Bile circulating free DNA (cfDNA) as a novel liquid biopsy method for the early clinical diagnosis of cholangiocarcinoma (CCA) has been less reported. Methods: We collected bile samples from 51 patients with CCA and 48 patients with gallstones at Shandong Provincial third Hospital from September 2022 to December 2023. We quantified bile cfDNA of syncytin-1 and SLC7A11,calculated the correlation bySpearman rank correlation, plotted Receiver Operating Characteristic (ROC) curves, and compared the Area Under Curve (AUC) values to explored early diagnostic utility in patients. Results: We first found the bile cfDNA of syncytin-1 and SLC7A11 levels in CCA were higher than in gallstones (p < 0.001; p < 0.001). And there was significant correlation between syncytin-1 and SLC7A11 expression (Spearman ’r = 0.458, p < 0.001). The AUC of bile cfDNA of syncytin-1 was 0.891(specificity of 90.2% and sensitivity of 75.0%), the AUC of bile cfDNA of SLC7A11 was 0.793 (specificity of 80.4% and sensitivity of 72.9%), and combination of bile cfDNA of syncytin-1/SLC7A11/CA19-9 markers improved diagnostic efficiency in CCA patients (AUC:0.901, p < 0.001). Conclusion: The bile cfDNA of syncytin-1 and SLC7A11 was high expression in cholangiocarcinoma, which may be used as a novel biomarker for early diagnosis.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Bile-derived cfDNA of syncytin-1 and SLC7A11 as a potential molecular marker for early diagnosis of cholangiocarcinoma

He,

Qian,

et al. 2024

Preprint

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“…Blood is the most broadly used type of liquid biopsy specimen in medical research. In addition to blood, body fluids such as saliva [5], sputum [6], cerebrospinal fluid [7][8][9][10][11], bile [12], urine [13][14][15][16][17][18][19][20][21], stool [22][23][24], seminal fluid [25], and uterine lavage fluid [26] have also been explored in a variety of malignancies (shown in Figure 1). There are many substances that can be used as liquid biopsy targets, including circulating tumor DNA (ctDNA), circulating miRNA, exosomes, and tumor-educated platelets (TEP), in addition to circulating tumor cells (CTCs) and circulating cell-free DNA (cfDNA), which are more widely used.…”

Section: Introductionmentioning

confidence: 99%

Clinical Application of Different Liquid Biopsy Components in Hepatocellular Carcinoma

Xu,

Zhao,

Chen

et al. 2024

JPM

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Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, usually occurring in the background of chronic liver disease. HCC lethality rate is in the third highest place in the world. Patients with HCC have concealed early symptoms and possess a high-level of heterogeneity. Once diagnosed, most of the tumors are in advanced stages and have a poor prognosis. The sensitivity and specificity of existing detection modalities and protocols are suboptimal. HCC calls for more sophisticated and individualized therapeutic regimens. Liquid biopsy is non-invasive, repeatable, unaffected by location, and can be monitored dynamically. It has emerged as a useable aid in achieving precision malignant tumor treatment. Circulating tumor cells (CTCs), circulating nucleic acids, exosomes and tumor-educated platelets are the commonest components of a liquid biopsy. It possesses the theoretical ability to conquer the high heterogeneity and the difficulty of early detection for HCC patients. In this review, we summarize the common enrichment techniques and the clinical applications in HCC for different liquid biopsy components. Tumor recurrence after HCC-related liver transplantation is more insidious and difficult to treat. The clinical use of liquid biopsy in HCC-related liver transplantation is also summarized in this review.

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“…Cholangiocarcinoma (CCA) consists a group of malignant tumours originating from the bile duct epithelium. [1][2][3] CCA, a type of bile duct cancer, is classified into two main subtypes based on its anatomical location: intrahepatic CCA (iCCA) and extrahepatic CCA (eCCA).…”

Section: Introductionmentioning

confidence: 99%

SMAD4 regulates the progression of cholangiocarcinoma by modulating the expression of STING1

Shi,

Zhao,

Sheng

et al. 2023

J Cellular Molecular Medi

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SMAD4 is a tumour suppressor and an important regulator of tumour immune scape which is downregulated in cholangiocarcinoma (CCA). STING1 is a vital sensing factor of abnormal DNA; however, the correlation between SMAD4 and STING1 and the role of the SMAD4‐STING1 interaction in the progression of CCA have not yet been evaluated. Public database was analysed to reveal the expression of SMAD4 and STING1. A cohort comprising 50 iCCA, 113 pCCA and 119 dCCA patients was assembled for the study. Immunohistochemistry was employed to evaluate the expression levels of STING1 and SMAD4. In vitro transwell and CCK8 assays, along with luciferase reporter assay, were conducted to analyse the potential regulatory mechanisms of SMAD4 on the expression of STING1. Expression of SMAD4 and STING1 were downregulated in CCA tumours and STING1 expression correlated with SMAD4 expression. The overexpression of SMAD4 was found to suppress the migration, invasion and proliferation capabilities of CCA cells; whereas, the knockdown of SMAD4 enhanced these abilities. Furthermore, it was observed that SMAD4 translocated into the nucleus following TGF‐β1 stimulation. Knockdown of SMAD4 resulted in the inhibition of STING1 transcriptional activity, whereas the overexpression of SMAD4 promoted the transcriptional activity of STING1. Clinically, low STING1 and SMAD4 expression indicated poor prognosis in CCA, and simultaneously low expression of STING1 and SMAD4 predicts poorer patient survival. SMAD4 regulates the expression of STING1 through its transcription regulating function. Dual low expression of STING1 and SMAD4 had more power in predicting patient survival. These results indicate that SMAD4‐silenced CCA may downregulate its STING1 expression to adapt to the immune system.

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Research progress of bile biomarkers and their immunoregulatory role in biliary tract cancers

Cited by 7 publications

References 133 publications

Bile-derived cfDNA of syncytin-1 and SLC7A11 as a potential molecular marker for early diagnosis of cholangiocarcinoma

Bile-derived cfDNA of syncytin-1 and SLC7A11 as a potential molecular marker for early diagnosis of cholangiocarcinoma

Clinical Application of Different Liquid Biopsy Components in Hepatocellular Carcinoma

SMAD4 regulates the progression of cholangiocarcinoma by modulating the expression of STING1

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