The tireless search to improve the prognostic assessment of intrahepatic cholangiocarcinoma: An urgent need

Muñoz-Martínez, Sergio; Forner, Alejandro

doi:10.1111/liv.14768

Cited by 3 publications

(3 citation statements)

References 12 publications

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“…Intrahepatic cholangiocarcinoma (ICC) is a rare (0.79 cases per 100,000 individuals) but often fatal malignancy originating from the epithelium of the secondary bile duct and its branches (1,2). ICC is the second most common primary liver malignancy after hepatocellular carcinoma (HCC), and the incidence of ICC has increased globally over the last decades, whereas the incidence of perihilar cholangiocarcinoma and distal cholangiocarcinoma has decreased (3)(4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Integrin β5 is an independent prognostic marker for intrahepatic cholangiocarcinoma in a Chinese population

Ma,

Song,

Zang

2023

Exp Ther Med

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Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor and a major cause of cancer mortality worldwide. Integrin β5 (ITGB5) is considered to be involved in the intercellular signal transduction and regulation of tumorigenesis and development. The present study investigated the association between ITGB5 expression levels and the prognosis of ICC, as well as the effects of ITGB5 on the proliferation and invasion of ICC cells. RNA-sequencing transcriptomic profiling data of ICC samples were retrieved from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Tissue specimens from patients with ICC treated at Taizhou People's Hospital were collected and the ITGB5 expression levels were evaluated using immunohistochemical staining. The biological function of ITGB5 in ICC was investigated using Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA) and in vitro experiments using HuCCT1 cells. After knocking down ITGB5 expression, cell proliferation was detected using Cell Counting Kit-8 assay, while cell invasion was assessed using Transwell assays. According to TCGA dataset, ITGB5 was highly expressed in ICC; however, there was no significant difference in prognosis between patients with high and low ITGB5 expression levels. High expression of ITGB5 was present in the tissues of patients with ICC from the GEO database, which was associated with poor prognosis. Survival analyses of the clinical data obtained in the present study revealed that high expression levels of ITGB5 in patients with ICC were associated with a reduced overall survival. GO and GSEA indicated that genes associated with ITGB5 were enriched in the extracellular matrix-receptor interaction and focal adhesion signaling pathways. Silencing ITGB5 inhibited the proliferation and invasion of ICC cells. In conclusion, ITGB5 may act as an essential regulator of ICC development and progression by influencing the proliferation and invasion of ICC cells. However, future studies with larger sample sizes are required to validate the role of ITGB5 in the prognosis of patients with ICC.

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Section: Introductionmentioning

confidence: 99%

Integrin β5 is an independent prognostic marker for intrahepatic cholangiocarcinoma in a Chinese population

Ma,

Song,

Zang

2023

Exp Ther Med

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“…The search for prognostic tools for iCCA is a hot topic. 12 , 13 The determinants of post‐progression survival (PPS) after a frontline therapy for iCCA have been scantly investigated. 14 The pattern of radiological progression has been shown to be an important driver of PPS in HCC progressing to sorafenib 15 , 16 and in extrahepatic malignancies.…”

Section: Introductionmentioning

confidence: 99%

“…The search for prognostic tools for iCCA is a hot topic 12,13 . The determinants of post‐progression survival (PPS) after a frontline therapy for iCCA have been scantly investigated 14 .…”

Section: Introductionmentioning

confidence: 99%

Pattern of progression of intrahepatic cholangiocarcinoma: Implications for second‐line clinical trials

Tovoli

Garajová

Gelsomino

et al. 2021

Liver International

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Background Intrahepatic cholangiocarcinoma (iCCA) is the second most frequent liver cancer. The overall survival of iCCA and other biliary tract cancers (BTC) remains poor. Recently, the ABC‐06 trial reported the superiority of FOLFOX vs clinical observation as a second‐line treatment. Still, the survival benefit was less than expected. We hypothesized that the pattern of progression of iCCA can drive post‐progression survival (PPS), similar to hepatocellular carcinoma. Methods Multicentre retrospective evaluation of consecutive iCCA patients who progressed after frontline systemic treatment with gemcitabine as monotherapy or in combination with platinum. Radiological assessment of progression was evaluated according to RECIST 1.1. The progression pattern was divided according to the presence/absence of new extrahepatic lesions (NEH). Results We included 206 patients from 5 centres. The median OS was 14.1 months and its independent predictors (hazard ratio [HR], 95% confidence interval [CI]) were previous surgery 0.699 [0.509‐0.961], performance status >2.445 [1.788‐3.344], permanent first‐line discontinuation 16.072 [5.102‐50.633], registration of ascites 2.226 [1.448‐3.420] or bilirubin >3 mg/dl 3.004 [1.935‐4.664] during the follow‐up, and disease progression 2.523 [1.261‐5.050]. The appearance of NEH independently predicted OS 2.18 [1.55‐3.06] in patients with radiological progression. Amongst 138 patients eligible for second‐line treatment, PPS was 16.8 and 5.9 months in cases without and with NEH, respectively (P = .001). Progression owing to NEH lesions was an independent predictor of PPS 1.873 [1.333‐2.662], together with performance status, time to progression to the frontline treatment, bilirubin >3 mg/dl and ascites. Conclusions PPS of iCCA is influenced by progression pattern, with important implications for second‐line trial design and analysis.

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A2M is a potential core gene in intrahepatic cholangiocarcinoma

et al. 2022

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Background Intrahepatic cholangiocarcinoma (ICC) is a type of malignant tumor ranking the second in the incidence of primary liver cancer following hepatocellular carcinoma. Both the morbidity and mortality have been increasing in recent years. Small duct type of ICC has potential therapeutic targets. But overall, the prognosis of patients with ICC is usually very poor. Methods To search latent therapeutic targets for ICC, we programmatically selected the five most suitable microarray datasets. Then, we made an analysis of these microarray datasets (GSE26566, GSE31370, GSE32958, GSE45001 and GSE76311) collected from the Gene Expression Omnibus (GEO) database. The GEO2R tool was effective to find out differentially expressed genes (DEGs) between ICC and normal tissue. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were executed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) v 6.8. The Search Tool for the Retrieval of Interacting Genes (STRING) database was used to analyze protein–protein interaction of these DEGs and protein–protein interaction of these DEGs was modified by Cytoscape3.8.2. Survival analysis was performed using Gene Expression Profiling Interactive Analysis (GEPIA) online analysis tool. Results A total of 28 upregulated DEGs and 118 downregulated DEGs were screened out. Then twenty hub genes were selected according to the connectivity degree. The survival analysis results showed that A2M was closely related to the pathogenesis and prognosis of ICC and was a potential therapeutic target for ICC. Conclusions According to our study, low A2M expression in ICC compared to normal bile duct tissue was an adverse prognostic factor in ICC patients. The value of A2M in the treatment of ICC needs to be further studied.

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The tireless search to improve the prognostic assessment of intrahepatic cholangiocarcinoma: An urgent need

Cited by 3 publications

References 12 publications

Integrin β5 is an independent prognostic marker for intrahepatic cholangiocarcinoma in a Chinese population

Integrin β5 is an independent prognostic marker for intrahepatic cholangiocarcinoma in a Chinese population

Pattern of progression of intrahepatic cholangiocarcinoma: Implications for second‐line clinical trials

A2M is a potential core gene in intrahepatic cholangiocarcinoma

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