Comprehensive genomic profile of cholangiocarcinomas in China

Shi

et al. 2021

Sci Rep

Self Cite

Ovarian cancer is one of the most common cancers in women and is often diagnosed as advanced stage because of the subtle symptoms of early ovarian cancer. To identify the somatic alterations and new biomarkers for the diagnosis and targeted therapy of Chinese ovarian cancer patients, a total of 65 Chinese ovarian cancer patients were enrolled for detection of genomic alterations. The most commonly mutated genes in ovarian cancers were TP53 (86.15%, 56/65), NF1 (13.85%, 9/65), NOTCH3 (10.77%, 7/65), and TERT (10.77%, 7/65). Statistical analysis showed that TP53 and LRP1B mutations were associated with the age of patients, KRAS, TP53, and PTEN mutations were significantly associated with tumor differentiation, and MED12, LRP2, PIK3R2, CCNE1, and LRP1B mutations were significantly associated with high tumor mutational burden. The mutation frequencies of LRP2 and NTRK3 in metastatic ovarian cancers were higher than those in primary tumors, but the difference was not significant (P = 0.072, for both). Molecular characteristics of three patients responding to olapanib supported that BRCA mutation and HRD related mutations is the target of olaparib in platinum sensitive patients. In conclusion we identified the somatic alterations and suggested a group of potential biomarkers for Chinese ovarian cancer patients. Our study provided a basis for further exploration of diagnosis and molecular targeted therapy for Chinese ovarian cancer patients.

Section: Methodsmentioning

confidence: 99%

A comprehensive analysis of somatic alterations in Chinese ovarian cancer patients

Shi

et al. 2021

Sci Rep

Self Cite

“…They analyzed the frequency and type of genetic aberrations in detail by comprehensive genomic profiling, and found the genomic heterogeneity between eastern and western patients of iCCA, but the relationship between TMB and prognosis was not mentioned. Besides, Tian et al investigated the comprehensive genomic features of Chinese patients with iCCA, and explored the relationship between TMB and some gene alternations [35]. It should be noted that TMB of their cohort was more than that in our study.…”

Section: Tp53 Rbm10 Kras and Ipo5mentioning

confidence: 60%

Comprehensive Analysis of Genomic Mutation Signature and Tumor Mutation Burden for Prognosis of Intrahepatic Cholangiocarcinoma

et al. 2020

Preprint

Background: The intrahepatic cholangiocarcinoma (iCCA) is highly lethal malignancy of biliary tract cancer. Analysis of somatic mutational profiling could help to reveal new prognostic markers and actionable targets for treatment. We aim to explore the impact of genomic mutation signature and tumor mutation burden (TMB) on prognosis of iCCA patients. Methods: The whole-exome sequencing and corresponding clinical data were collected from ICGC portal and cBioPortal database to detect the mutation prognostic genes and TMB values. To identify the hub prognostic mutant signature, Cox regression and Lasso feature selection were conducted. We built a mutation related signature (MRS) through multivariate Cox regression. The predictive performance of MRS and TMB were assessed using Kaplan-Meier (KM) analysis and receiver operating characteristic (ROC). We performed a functional enrichment pathway analysis with gene set enrichment analysis (GSEA) for mutated genes were conducted. Moreover, on the base of MRS, TMB and TNM stage, a nomogram was constructed to visualize the prognosis of iCCA patients.Results: The mutation landscape illustrated the distributions of mutation frequencies and types on iCCA, and revealed a list of most frequent mutation genes (such as Tp53, KRAS, ARID1A, IDH1). We obtain a 6- gene signature using the Lasso and Cox method. The AUC of MRS in 1, 3, 5-year OS prediction were 0.759, 0.732, 0.728, respectively. Moreover, Kaplan-Meier analysis showed a significant difference on the prognosis of iCCA with high and low MRS score (P <0.001). Interestingly, GSEA was utilized to show several signaling pathways including MAPK signaling pathway, PI3K-AKT signaling pathway and proteoglycans in cancer. On the other hand, survival analysis indicated that TMB was significantly associated with prognosis. And GSEA indicated that samples with high MRS or TMB upregulated signaling pathways involved in tumor signaling and immune system. At last, we constructed a predictive nomogram (included MRS, TMB and TNM stage) with satisfactory performance in survival prediction. Conclusions: The mutation genes signature and TMB were associated with prognosis in patients with iCCA. Our study provides a valuable prognostic predictor for further uncovering molecular pathogenesis in iCCA.

“…Similarly, they observed specificities expressed in iCCA (STK11, CCND1, FGF19, FGF3, FGF4 and PBRM1). For FGFR2, they are expressed in both Western and Chinese cohorts [ 7 ]. Through the cBioPortal website [ 29 , 30 ], we merged six clinical cohorts to analyze their genetic alteration events, survival time and the proportion of several demographic factors ( Figure 1 ).…”

Section: Genomics Alterations and Epigenetic Changes In Ccamentioning

confidence: 99%

“…Analyzing the annual mortality rate of CCA, the average mortality rate for the period 2010–2014 was 0.3–2.88 (per 1 × 10 5 inhabitants) [ 6 ]. However, higher mortality rates (>4, per 1 × 10 5 inhabitants) including China [ 7 ], Japan [ 8 ], South Korea [ 9 ], Thailand [ 10 ], Taiwan [ 11 ] and Austria [ 12 ]. It has also been confirmed that men have a higher odds ratio than women [ 13 ].…”

Section: Introduction To Ccamentioning

confidence: 99%

Omics-Based Platforms: Current Status and Potential Use for Cholangiocarcinoma

et al. 2020

Cholangiocarcinoma (CCA) has been identified as a highly malignant cancer that can be transformed from epithelial cells of the bile duct, including intrahepatic, perihilar and extrahepatic. High-resolution imaging tools (abdominal ultrasound, computed tomography and percutaneous transhepatic cholangial drainage) are recruited for diagnosis. However, the lack of early diagnostic biomarkers and treatment evaluation can lead to serious outcomes and poor prognosis (i.e., CA19-9, MUC5AC). In recent years, scientists have established a large number of omics profiles to reveal underlying mechanisms and networks (i.e., IL-6/STAT3, NOTCH). With these results, we achieved several genomic alteration events (i.e., TP53mut, KRASmut) and epigenetic modifications (i.e., DNA methylation, histone modification) in CCA cells and clinical patients. Moreover, we reviewed candidate gene (such as NF-kB, YAP1) that drive gene transcription factors and canonical pathways through transcriptomics profiles (including microarrays and next-generation sequencing). In addition, the proteomics database also indicates which molecules and their directly binding status could trigger dysfunction signatures in tumorigenesis (carbohydrate antigen 19-9, mucins). Most importantly, we collected metabolomics datasets and pivotal metabolites. These results reflect the pharmacotherapeutic options and evaluate pharmacokinetic/pharmacodynamics in vitro and in vivo. We reversed the panels and selected many potentially small compounds from the connectivity map and L1000CDS2 system. In this paper, we summarize the prognostic value of each candidate gene and correlate this information with clinical events in CCA. This review can serve as a reference for further research to clearly investigate the complex characteristics of CCA, which may lead to better prognosis, drug repurposing and treatment strategies.