Low expression of ARID1A correlates with poor prognosis in intrahepatic cholangiocarcinoma

Yang, Songzhu; Wang, An-Qiang; Du, Juan; Wang, Jiantao; Yu, Weiwei; Liu, Qing; Wu, Yao; Chen, Shuguang

doi:10.3748/wjg.v22.i25.5814

Cited by 16 publications

(16 citation statements)

References 33 publications

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“…Differently, to date only low expression of ARID1A protein and mRNA were associated to poor prognosis in 57 intrahepatic cholangiocarcinomas analysed by Yang and colleagues. Although this corroborates our finding in suggesting a prognostic role of ARID1A in ICC, unfortunately no mutational analysis was performed in that study 28 . Furthermore, a recent meta-analysis of Luchini et al .…”

Section: Discussionsupporting

confidence: 92%

Genetic alterations analysis in prognostic stratified groups identified TP53 and ARID1A as poor clinical performance markers in intrahepatic cholangiocarcinoma

Simbolo¹,

Vicentini²,

Ruzzenente

et al. 2018

Sci Rep

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The incidence and mortality rates of intrahepatic cholangiocarcinoma have been rising worldwide. Few patients present an early-stage disease that is amenable to curative surgery and after resection, high recurrence rates persist. To identify new independent marker related to aggressive behaviour, two prognostic groups of patient were selected and divided according to prognostic performance. All patients alive at 36 months were included in good prognostic performers, while all patients died due to disease within 36 months in poor prognostic performers. Using high-coverage target sequencing we analysed principal genetic alterations in two groups and compared results to clinical data. In the 33 cases included in poor prognosis group, TP53 was most mutated gene (p = 0.011) and exclusively present in these cases. Similarly, ARID1A was exclusive of this group (p = 0.024). TP53 and ARID1A are mutually exclusive in this study. Statistical analysis showed mutations in TP53 and ARID1A genes and amplification of MET gene as independent predictors of poor prognosis (TP53, p = 0.0031, ARID1A, p = 0.0007, MET, p = 0.0003 in Cox analysis). LOH in PTEN was also identified as marker of disease recurrence (p = 0.04) in univariate analysis. This work improves our understanding of aggressiveness related to this tumour type and has identified novel prognostic markers of clinical outcome.

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Section: Discussionsupporting

confidence: 92%

Genetic alterations analysis in prognostic stratified groups identified TP53 and ARID1A as poor clinical performance markers in intrahepatic cholangiocarcinoma

Simbolo¹,

Vicentini²,

Ruzzenente

et al. 2018

Sci Rep

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“…6 Therefore, identification of novel therapeutic molecular targets is essential for improving the prognosis of ICC. 7,8 NRP1 was first discovered as an adhesion molecule in the frog nervous system in 1987. 9 It is a non-tyrosine kinase transmembrane glycoprotein located on the cell surface and plays a role of a co-receptor for secreted Semaphorin-3A (Sema3A).…”

Section: Introductionmentioning

confidence: 99%

<p>NRP1 is a Prognostic Factor and Promotes the Growth and Migration of Cells in Intrahepatic Cholangiocarcinoma</p>

Bai

et al. 2020

CMAR

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Background: Neuropilin-1 (NRP-1) participates in cancer cell proliferation and metastasis as a multifunctional co-receptor by interacting with multiple signaling pathways. However, few studies have addressed the precise function and prognosis analysis of NRP1 in intrahepatic cholangiocarcinoma (ICC). We aimed to study the correlations between NRP1 and clinicopathological characteristics and NRP1 effect on ICC cell line functions. Methods: NRP1 mRNA and its protein levels in human ICC tissues and cell lines were detected by IHC, qRT-PCR, and WB method. Transwell, wound healing, and CCK-8 assays were performed to verify the effects of NRP1 knockdown and overexpression on cell migration and proliferation capability. Results: NRP1 proteins and mRNA levels increased in ICC tissues compared to those in paired adjacent non-tumor tissues. High NRP1 expression of ICC tissues was related to poor prognosis. NRP1 expression level was expected to be an independent prognosticator for overall survival and cumulative tumor recurrence, and was closely related to tumor number (P=0.047). Knockdown of NRP1 inhibited cell proliferation and migration capability of RBE cells in vitro, and NRP1 overexpression in 9810 cells accelerated proliferation and migration. Additionally, NRP1 may promote cell proliferation and migration in ICC via the FAK/PI3-K/ AKT pathway. Conclusion: As an oncogene, NRP1 may function as a candidate target and prognostic biomarker of value for ICC therapy.

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“…Despite that the NGS panel was originally tailored for analyzing patients with CRC, several of the detected mutations have suggested clinicopathological features and involvement in the tumorigenesis of BTC. Mutations in ARID1A has been associated with poor prognosis and TP53 and KRAS, conventionally classified as a tumor suppressor and oncogene, respectively, may play an intriguing role in the plasticity of hepatocytes and cholangiocytes during the early tumorigenesis . However, the phenotypic consequences of mutational aberrations are for most of the genes still vastly under‐reported, and future work may elucidate the specific role in tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Exome sequencing of 22 genes using tissue from patients with biliary tract cancer

Høgdall

Larsen

Linnemann

et al. 2019

APMIS

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Biliary tract cancers (BTC) are a rare heterogeneous disease group with a dismal prognosis and limited treatment options. The mutational landscape consists of genetic aberrations both shared by and characteristic for anatomical location. Here, we present exome sequencing data on 22 genes from a phase 2 trial using a clinically validated panel used in patients with colorectal cancer. A total of 56 patients were included in a one‐armed phase 2 trial investigating the treatment combination of capecitabine, gemcitabine, oxaliplatin, and cetuximab. Tissue DNA yield and quality allowed analysis of 30 patients on our panel including 22 genes. ARID1A (33%) and TP53 (33%) were found to be most frequently mutated followed by KRAS mutations found in 20% of the patients. Mutational aberrations in ARID1A were found more prevalent than expected, whereas TP53 and KRAS were in concordance with earlier reported data. Mutation in CTNNB1 was significantly associated with poor prognosis. Our panel is clinically validated and suitable for a high volume of samples to detect mutations in patients with BTC. However, it is reasonable to assume that the clinical utility could be optimized in this patient group by extending the panel to include BTC specific mutations with potential therapeutic consequences such as IDH1/2, FGFR fusions, ERBB3, and BRCA1/2.

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Low expression of ARID1A correlates with poor prognosis in intrahepatic cholangiocarcinoma

Abstract: Low expression of ARID1A is associated with poor prognosis in patients with IHCC, and thus may be a potential prognostic biomarker candidate in IHCC.

Cited by 16 publications

References 33 publications

Genetic alterations analysis in prognostic stratified groups identified TP53 and ARID1A as poor clinical performance markers in intrahepatic cholangiocarcinoma

Genetic alterations analysis in prognostic stratified groups identified TP53 and ARID1A as poor clinical performance markers in intrahepatic cholangiocarcinoma

<p>NRP1 is a Prognostic Factor and Promotes the Growth and Migration of Cells in Intrahepatic Cholangiocarcinoma</p>

Exome sequencing of 22 genes using tissue from patients with biliary tract cancer

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