Comprehensive analysis of genomic alterations of Chinese hilar cholangiocarcinoma patients

Feng, Feiling; Wu, Xiaobing; Shi, Xiaoliang; Gao, Qingxiang; Wu, Yue; Yu, Yang; Cheng, Qiang; Li, Bin; Yi, Bin; Liu, Chen; Hao, Qing; Zhang, Lin; Gao, Chunfang; Jiang, Xiaoqing

doi:10.1007/s10147-020-01846-z

Cited by 11 publications

(8 citation statements)

References 56 publications

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“…The specific mutations include IDH1, MCL1, PBRM1, FGFR2, and FGFR 3/4/19 in iCCA, and FBXW7, ERBB2, and RBM10 in exCCA (10,11). Previous studies have also shown the genomic heterogeneity of CCA subtypes, potentially affecting future therapy trials (12). Waseem et al reported that the mean survival of pCCA is lower than that of dCCA, but is similar to iCCA (13).…”

Section: Introductionmentioning

confidence: 99%

Specific genomic alterations and prognostic analysis of perihilar cholangiocarcinoma and distal cholangiocarcinoma

Zheng¹,

Qin²,

Gong³

et al. 2021

J Gastrointest Oncol

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Background: Cholangiocarcinoma (CCA), which consists of intrahepatic CCA (iCCA), perihilar CCA (pCCA), and distal CCA (dCCA), is an aggressive malignancy worldwide. PCCA and dCCA are often classified as extrahepatic CCA (exCCA). However, the differences in mutational characteristics between pCCA and dCCA remain unclear.Methods: Deep sequencing targeting of 450 cancer genes was performed for genomic alteration detection.The tumor mutational burden (TMB) was measured by an algorithm developed in-house. Correlation analysis was conducted using Fisher's exact test.Results: FGFR2 and ERBB2 mutations mainly occurred in iCCA and exCCA, respectively. In exCCA, the frequencies of PIK3CA, FAT4, KDM6A, MDM2, and TCF7L2 mutations were significantly higher in pCCA compared to dCCA, while the frequencies of TP53 and KRAS mutations were markedly lower in pCCA than those in dCCA. The prognosis-related mutations were different among the CCA subtypes. NF1 mutation was associated with short disease-free survival (DFS) and overall survival (OS), and ERBB2 mutation was associated with short DFS in dCCA patients. Meanwhile, MAP2K4 mutation was associated with long DFS and OS, and TERT mutation was associated with short DFS in pCCA. A series of mutations in genes, including ARID1A, ARID2, SMAD4, TERT, TP53, and KRAS, were found to be associated with the TMB.Conclusions: In this study, we investigated the comprehensive genomic characterizations of CCA patients, identified the significant alterations in each subtype, and identified potential biomarkers for prognosis prediction. These results provide molecular evidence for the heterogeneity of CCA subtypes and evidence for further precision targeted therapy of CCA patients.

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Section: Introductionmentioning

confidence: 99%

Specific genomic alterations and prognostic analysis of perihilar cholangiocarcinoma and distal cholangiocarcinoma

Zheng¹,

Qin²,

Gong³

et al. 2021

J Gastrointest Oncol

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“…A pronounced difference in PD-L1 induction by IFN-γ treatment existed between ARID1A -deficient and control gastric cancer cells ( 30 ). Downregulation of ARID2 inhibited DNA methyltransferase, which increased methylation in the promoter region and increased the transcription of IFN-γ ( 31 ). Therefore, similar downstream mechanisms of ARIDs might share common characteristics in tumour regulation, and we could utilise these findings for the further investigation of other genes in digestive cancer.…”

Section: Discussionmentioning

confidence: 99%

Expression Signature of the AT-Rich Interactive Domain Gene Family Identified in Digestive Cancer

Liu

Wang

et al. 2022

Front. Med.

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BackgroundThe AT-rich interactive domain (ARID) gene family of 15 proteins has an important role in development and proliferation. Gene expression alterations of the ARID family are correlated with the pathogenesis of digestive cancer, but systematic research has not been conducted.MethodsWe obtained transcriptome sequencing data, clinical characteristics and stemness indices of the seven main types of digestive cancer (cholangiocarcinoma, colon adenocarcinoma, oesophageal carcinoma, liver hepatocellular carcinoma, pancreatic adenocarcinoma, rectum adenocarcinoma and stomach adenocarcinoma) from public pan-cancer data to combine the analysis of the expression and prognostic signature of the ARID gene family. The stromal and immune scores for each sample were calculated to explore the correlations between the ARID gene family members and the tumour microenvironment.ResultsAfter screening, 1,920 digestive cancer samples were included in our study. ARID3C was expressed at low levels throughout the digestive cancer samples. The expression levels of ARID1A and JARID1C were relatively high, but there was striking heterogeneity across the different cancer types for specific family members. The survival analysis indicated that many genes were significantly related to the prognosis of patients with liver hepatocellular carcinoma. The stemness indices, stromal score, and immune score analysis showed that the expression of a single ARID gene had characteristic consistency in each tumour, but the levels among the different genes still varied.ConclusionOur systematic study of the ARID gene family and its association with the immune infiltrate, tumour microenvironment and outcomes of digestive cancer patients focus on the complex relations and indicate the need to study each ARID member as an individual in a specific cancer type.

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Section: Discussionmentioning

confidence: 99%

“…Moreover, there are several available prognostic tools and clinical factors which obviously improve the prediction and accurate stratification of patient prognosis [ 19 , 36 , 43 ]. However, currently published data in this context have focused almost exclusively on clinical characteristics such as age, sex, tumor-related factors, etc., whereas BMI or/and appearance of overweight and obesity is left behind [ 32 , 33 , 34 , 43 ]. Therefore, the results of this study were of enormous importance, as we were able to demonstrate that if recording BMI as a prognostic factor in clinical research an independent association between increasing patients BMI and incremental development of recurrence risk following curative liver resection among patients with pCAA was observed.…”

Section: Discussionmentioning

confidence: 99%

Impact of Body Mass Index on Tumor Recurrence in Patients Undergoing Liver Resection for Perihilar Cholangiocarcinoma (pCCA)

Hau

Devantier

Jahn

et al. 2021

Cancers

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Background: The association of body mass index (BMI) and long-term prognosis and outcome of patients with perihilar cholangiocarcinoma (pCCA) has not been well defined. The aim of this study was to evaluate clinicopathologic and oncologic outcomes with pCCA undergoing resection, according to their BMI. Methods: Patients undergoing liver resection in curative intention for pCCA at a tertiary German hepatobiliary (HPB) center were identified from a prospective database. Patients were classified as normal weight (BMI 18.5–24.9 kg/m2), overweight (BMI 25.0–29.9 kg/m2) and obese (>30 kg/m2) according to their BMI. Impact of clinical and histo-pathological characteristics on recurrence-free survival (RFS) were assessed using Cox proportional hazard regression analysis among patients of all BMI groups. Results: Among a total of 95 patients undergoing liver resection in curative intention for pCCA in the analytic cohort, 48 patients (50.5%) had normal weight, 33 (34.7%) were overweight and 14 patients (14.7%) were obese. After a median follow-up of 4.3 ± 2.9 years, recurrence was observed in totally 53 patients (56%). The cumulative recurrence probability was higher in obese and overweight patients than normal weight patients (5-year recurrence rate: obese: 82% versus overweight: 81% versus normal weight: 58% at 5 years; p = 0.02). Totally, 1-, 3-, 5- and 10-year recurrence-free survival rates were 68.5%, 44.6%, 28.9% and 13%, respectively. On multivariable analysis, increased BMI (HR 1.08, 95% CI: 1.01–1.16; p = 0.021), poor/moderate tumor differentiation (HR 2.49, 95% CI: 1.2–5.2; p = 0.014), positive lymph node status (HR 2.01, 95% CI: 1.11–3.65; p = 0.021), positive resection margins (HR 1.89, 95% CI:1.02–3.4; p = 0.019) and positive perineural invasion (HR 2.92, 95% CI: 1.02–8.3; p = 0.045) were independent prognostic risk factors for inferior RFS. Conclusion: Our study shows that a high BMI is significantly associated with an increased risk of recurrence after liver resection in curative intention for pCCA. This factor should be considered in future studies to better predict patient’s individual prognosis and outcome based on their BMI.

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Comprehensive analysis of genomic alterations of Chinese hilar cholangiocarcinoma patients

Cited by 11 publications

References 56 publications

Specific genomic alterations and prognostic analysis of perihilar cholangiocarcinoma and distal cholangiocarcinoma

Specific genomic alterations and prognostic analysis of perihilar cholangiocarcinoma and distal cholangiocarcinoma

Expression Signature of the AT-Rich Interactive Domain Gene Family Identified in Digestive Cancer

Impact of Body Mass Index on Tumor Recurrence in Patients Undergoing Liver Resection for Perihilar Cholangiocarcinoma (pCCA)

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