Dataset Information

Clonorchis sinensis infection amplifies hepatocellular carcinoma stemness, predicting unfavorable prognosis.

ABSTRACT:

Background

Extensive evidence links Clonorchis sinensis (C. sinensis) to cholangiocarcinoma; however, its association with hepatocellular carcinoma (HCC) is less acknowledged, and the underlying mechanism remains unclear. This study was designed to investigate the association between C. sinensis infection and HCC and reveal the relationship between C. sinensis infection and cancer stemness.

Methods

A comprehensive analysis of 839 HCC patients categorized into C. sinensis (-) HCC and C. sinensis (+) HCC groups was conducted. Chi-square and Mann-Whitney U tests were used to assess the association between C. sinensis infection and clinical factors. Kaplan-Meier and Cox regression analyses were used to evaluate survival outcomes. Immunohistochemistry was used to determine CK19 and EpCAM expression in HCC specimens.

Results

Compared to C. sinensis (-) HCC patients, C. sinensis (+) HCC patients exhibited advanced Barcelona Clinic Liver Cancer (BCLC) stage, higher male prevalence and more liver cirrhosis as well as elevated alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), eosinophil, complement 3 (C3), and complement 4 (C4) values. C. sinensis infection correlated with shorter overall survival (OS) (p < 0.05) and recurrence-free survival (RFS) (p < 0.05). Furthermore, Cox multivariate analysis revealed that C. sinensis infection was an independent prognostic factor for OS in HCC patients. Importantly, C. sinensis infection upregulated the expression of HCC cancer stem cell markers CK19 and EpCAM.

Conclusion

HCC patients with C. sinensis infection exhibit a poor prognosis following hepatectomy. Moreover, C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC.

Author summary

Clonorchis sinensis (C. sinensis) is a prominent food-borne parasite prevalent in regions such as China, particularly in Guangxi. C. sinensis has been associated with various hepatobiliary system injuries, encompassing inflammation, periductal fibrosis, cholangiocarcinoma and even hepatocellular carcinoma (HCC). A substantial body of evidence links C. sinensis to cholangiocarcinoma, However, the connection between C. sinensis and HCC and the intricate mechanisms underlying its contribution to HCC development remain incompletely elucidated. Our study demonstrates clear clinicopathological associations between C. sinensis and HCC, such as gender, BCLC stage, liver cirrhosis, MVI, AFP, CA19-9, circulating eosinophils and complements. Furthermore, we found that the co-occurrence of C. sinensis exhibited a significant association with shorter OS and RFS in patients diagnosed with HCC. A major finding was that C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC. Our results provide a more comprehensive comprehension of the interplay between C. sinensis and HCC, shedding fresh light on the carcinogenic potential of C. sinensis.

SUBMITTER: Lin Q

PROVIDER: S-EPMC10824460 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Clonorchis sinensis infection amplifies hepatocellular carcinoma stemness, predicting unfavorable prognosis.

Lin Qiumei Q Tang Zeli Z Qin Yuling Y Deng Xueling X Wei Caibiao C Liu Fengfei F Pan Xiaolan X Liu Dengyu D Zhan Tingzheng T Fang Min M

PLoS neglected tropical diseases 20240129 1

<h4>Background</h4>Extensive evidence links Clonorchis sinensis (C. sinensis) to cholangiocarcinoma; however, its association with hepatocellular carcinoma (HCC) is less acknowledged, and the underlying mechanism remains unclear. This study was designed to investigate the association between C. sinensis infection and HCC and reveal the relationship between C. sinensis infection and cancer stemness.<h4>Methods</h4>A comprehensive analysis of 839 HCC patients categorized into C. sinensis (-) HCC a ...[more]

PMID: 38285640

Similar Datasets

Project description:BackgroundThis study aimed to determine the impact of co-infection of Clonorchis sinensis (CS) and hepatitis B virus (HBV) on the prognosis of patients with hepatocellular carcinoma (HCC) following hepatectomy.MethodsThe clinicopathological information of 946 patients with HCC following hepatectomy was retrospectively analyzed. The patients were divided into four groups depending on whether they had CS infection and/or HBV infection: double-negative group (infected with neither CS nor HBV), simple CS group (infected with only CS), simple HBV group (infected with only HBV), and double-positive group (co-infected with CS and HBV). Kaplan-Meier curves were used to evaluate the overall survival (OS) and recurrence-free survival (RFS), while log-rank tests were used to compare survival rates. Further, Cox regression was used to perform both univariate and multivariate survival analyses to identify variables linked to the prognosis of HCC.ResultsThe median overall survival (OS) and recurrence-free survival (RFS) in the double-positive, simple CS, simple HBV, and double-negative groups were 27 months and 9 months, 20 months and 7 months, 44 months and 12 months, and 42 months and 17 months, respectively. The double-positive group's 1-year, 3-year, and 5-year OS and RFS rates were 79.2% and 46.9%, 62.6% and 28.4%, 47.8%, and 12.2%, respectively. The simple CS group's 1-year, 3-year, and 5-year OS and RFS rates were 86.3% and 41.5%, 56.5% and 27.7%, 50.2%, and 18.5%, respectively. The simple HBV group's 1-year, 3-year, and 5-year OS and RFS rates were 89.8% and 56.0%, 72.5% and 30.5%, 63.8%, and 19.9%, respectively. The double-negative group's 1-year, 3-year, and 5-year OS and RFS rates were 91.5% and 62.3%, 76.1% and 32.9%, 64.0%, and 22.4%, respectively. Further, according to a Cox multivariate analysis, tumor size (> 5cm), Edmonson grade (III-IV), BCLC-C stage, and tumor satellite focus were independent risk factors for RFS and OS in patients with HCC.ConclusionPatients with HCC and Clonorchis sinensis infection experience a poor prognosis after hepatectomy, regardless of whether they are co-infected with HBV.

Project description:BackgroundHepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally, and its progression is associated with various factors, including parasitic infections such as Clonorchis sinensis (C. sinensis). Although C. sinensis infection has been implicated in HCC, the molecular mechanisms, particularly the role of microRNAs (miRNAs), remain poorly understood. This study aims to fill this gap by investigating the miRNA expression profiles in C. sinensis+ and C. sinensis- HCC tissues.MethodWe performed miRNA sequencing on HCC tissues from C. sinensis+ and C. sinensis- patients, followed by bioinformatics analyses to identify differentially expressed miRNAs (DEMs) and their target genes. Gene Ontology (GO) enrichment analysis was conducted to explore relevant biological processes, while a competitive endogenous RNA (ceRNA) network was constructed to investigate the interactions among miRNAs, long noncoding RNAs (lncRNAs), and messenger RNAs (mRNAs). Additionally, we performed survival analysis using Gene Expression Profiling Interactive Analysis 2 (GEPIA2) based on the The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort and assessed the clinical relevance of DEMs. Key miRNAs identified from this analysis were further validated through quantitative real‑time polymerase chain reaction (qRT-PCR) assays to confirm their expression in MHCC97H.ResultsOur research identified significant miRNA dysregulation in C. sinensis+ HCC tumors compared with C. sinensis- HCC tumors. Notably, miR-143-3p, miR-10a-5p, and miR-100-5p were upregulated in C. sinensis+ HCC, contributing to immune responses and tumor progression, while let-7 family members and miR-221-3p were downregulated, affecting metabolic pathways. GO enrichment analysis highlighted the involvement of developmental processes, immune system regulation, and metabolic reprogramming in C. sinensis+ HCC. The construction of a ceRNA network revealed key interactions between miRNAs, lncRNAs, and mRNAs in C. sinensis+ HCC, suggesting regulatory mechanisms that could be potential therapeutic targets. Additionally, validation through qRT-PCR confirmed these findings, highlighting miRNA dysregulation as a critical factor in C. sinensis+ HCC progression.ConclusionsThis study provides novel insights into the role of miRNAs in C. sinensis-infected HCC progression. The findings highlight the critical role of miRNA dysregulation in the progression of C. sinensis-associated HCC, emphasizing the potential for therapeutic interventions targeting these molecular alterations in affected patients.

Dataset Information

Clonorchis sinensis infection amplifies hepatocellular carcinoma stemness, predicting unfavorable prognosis.

Background

Methods

Results

Conclusion

Author summary

Publications

Clonorchis sinensis infection amplifies hepatocellular carcinoma stemness, predicting unfavorable prognosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets