Reproduction of the Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG) Gastric Cancer Molecular Classifications and Their Association with Clinicopathological Characteristics and Overall Survival in Moroccan Patients

Introduction. The Cancer Genome Atlas (TCGA) project and Asian Cancer Research Group (ACRG) recently categorized gastric cancer into molecular subtypes. Nevertheless, these classification systems require high cost and sophisticated molecular technologies, preventing their widespread use in the clinic. This study is aimed to generating molecular subtypes of gastric cancer using techniques available in routine diagnostic practice in a series of Moroccan gastric cancer patients. In addition, we assessed the associations between molecular subtypes, clinicopathological features, and prognosis. Methods. Ninety-seven gastric cancer cases were classified according to TCGA, ACRG, and integrated classifications using a panel of four molecular markers (EBV, MSI, E-cadherin, and p53). HER2 status and PD-L1 expression were also evaluated. These markers were analyzed using immunohistochemistry (E-cadherin, p53, HER2, and PD-L1), in situ hybridization (EBV and HER2 equivocal cases), and multiplex PCR (MSI). Results. Our results showed that the subtypes presented distinct clinicopathological features and prognosis. EBV-positive gastric cancers were found exclusively in male patients. The GS (TCGA classification), MSS/EMT (ACRG classification), and E-cadherin aberrant subtype (integrated classification) presented the Lauren diffuse histology enrichment and tended to be diagnosed at a younger age. The MSI subtype was associated with a better overall survival across all classifications (TCGA, ACRG, and integrated classification). The worst prognosis was observed in the EBV subtype (TCGA and integrated classification) and MSS/EMT subtype (ACRG classification). Discussion/Conclusion. We reported a reproducible and affordable gastric cancer subtyping algorithms that can reproduce the recently recognized TCGA, ACRG, and integrated gastric cancer classifications, using techniques available in routine diagnosis. These simplified classifications can be employed not only for molecular classification but also in predicting the prognosis of gastric cancer patients.

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Clinical Significance of Four Molecular Subtypes of Gastric Cancer Identified by The Cancer Genome Atlas Project

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-16-2211 ◽

2017 ◽

Vol 23 (15) ◽

pp. 4441-4449 ◽

Cited By ~ 103

Author(s):

Bo Hwa Sohn ◽

Jun-Eul Hwang ◽

Hee-Jin Jang ◽

Hyun-Sung Lee ◽

Sang Cheul Oh ◽

...

Keyword(s):

Gastric Cancer ◽

Clinical Significance ◽

Molecular Subtypes ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Cancer Genome Atlas ◽

Genome Atlas

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The 2nd Conference and Workshop of The Cancer Genome Atlas (TCGA) in India: Towards Team Science for Multi-omics Cancer Research in South Asia

ecancermedicalscience ◽

10.3332/ecancer.2021.ed111 ◽

2021 ◽

Vol 15 ◽

Author(s):

Santosh Dixit ◽

Anguraj Sadanandam

Keyword(s):

Cancer Research ◽

South Asia ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Team Science ◽

Cancer Genome Atlas ◽

Genome Atlas

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Identification of Aneuploid Circulating Tumor Cells in Soft-Tissue Sarcoma Patients: A Pilot Study

Oncology ◽

10.1159/000509326 ◽

2020 ◽

Vol 98 (12) ◽

pp. 893-896

Author(s):

Andrea Napolitano ◽

Alessandro Minelli ◽

Daniele Santini ◽

Giuseppe Tonini ◽

Bruno Vincenzi

Keyword(s):

Overall Survival ◽

Pilot Study ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Tumor Cells ◽

In Silico ◽

The Cancer Genome Atlas ◽

Cancer Genome Atlas ◽

First Time ◽

Genome Atlas

Background: Circulating tumor cells (CTCs) have been identified and shown to have prognostic and predictive roles in several types of carcinoma. More recently, aneuploid CTCs have become subject of a growing interest, as aneuploidy is considered a hallmark of cancer often associated with poor prognosis. Here, we aimed to identify for the first time aneuploid CTCs in soft-tissue sarcoma (STS) patients and show supportive in silico evidence on the prognostic role of aneuploidy in mesenchymal cancers. Methods: In our pilot study, we collected blood from 4 metastatic STS patients and 4 age- and sex-matched healthy controls. After sample processing, cells were cyto-centrifuged onto glass slides and FISH was performed using 5 probes. The in silico analysis was performed using data from The Cancer Genome Atlas cohort of STS patients, using the validated Aneuploidy Score. We divided the patients in two populations (aneuploidy-high, Ane-Hi, and aneuploidy-low, Ane-Lo) using the median value of the Aneuploidy Score as a cutoff. Kaplan-Meier curves associated with log-rank test were used to compare progression-free and overall survival between groups. GraphPad Prism 8.0 (La Jolla, CA, USA) was used for statistical analyses. Results: Aneuploid CTCs were identified in all 4 STS patients and in none of the controls, with a median value of 4 (range 3–6) per 7 mL of blood. Ane-Hi patients showed a significantly worse progression-free and overall survival compared to Ane-Lo patients. The same trend was maintained when analyzing the data based on the different histologies. Conclusions: We identified for the first time aneuploid CTCs in STS patients using fluorescence in situ hybridization in a surface marker-independent way. We also showed that the Aneuploidy Score has a prognostic value both in terms of progression-free survival and overall survival in STS patients using The Cancer Genome Atlas data, regardless of the histology.

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Why MUC16 mutations lead to a better prognosis: A study based on The Cancer Genome Atlas gastric cancer cohort

World Journal of Clinical Cases ◽

10.12998/wjcc.v9.i17.4143 ◽

2021 ◽

Vol 9 (17) ◽

pp. 4143-4158

Author(s):

Yu-Jie Huang ◽

Zhi-Fei Cao ◽

Jie Wang ◽

Jian Yang ◽

Yi-Jun Wei ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Cancer Genome Atlas ◽

Genome Atlas

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Candidate genes for predicting the survival of patients with gastric cancer: a study based on The Cancer Genome Atlas (TCGA) database

Translational Cancer Research ◽

10.21037/tcr.2020.02.82 ◽

2020 ◽

Vol 9 (4) ◽

pp. 2599-2608

Author(s):

Xiqiao Liu ◽

Liying Gao ◽

Dongqiong Ni ◽

Chengao Ma ◽

Yuping Lu ◽

...

Keyword(s):

Gastric Cancer ◽

Candidate Genes ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Cancer Genome Atlas ◽

Genome Atlas

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The role of miR-92b in cholangiocarcinoma patients

The International Journal of Biological Markers ◽

10.1177/1724600817751524 ◽

2018 ◽

Vol 33 (3) ◽

pp. 293-300 ◽

Cited By ~ 3

Author(s):

Min-hang Zhou ◽

Hong-wei Zhou ◽

Mo Liu ◽

Jun-zhong Sun

Keyword(s):

Gene Expression ◽

Overall Survival ◽

Gene Expression Omnibus ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Positive Regulation ◽

Cancer Genome Atlas ◽

High Level ◽

Genome Atlas

Purpose: The role of microRNA (miRNA) in cholangiocarcinoma was not clear. The aim of this study was to find the potential diagnostic and prognostic miRNA in cholangiocarcinoma patients. Methods: The miRNA expression profiles in cholangiocarcinoma patients from The Cancer Genome Atlas and Gene Expression Omnibus (GSE53870) were analyzed. The comparison of overall survival was performed using the Kaplan–Meier method. The targeted genes of prognostic miRNA were identified in miRanda, PicTar, or TargetScan, and their cell signaling pathways were analyzed by the Database for Annotation, Visualization and Integrated Discovery. Results: In The Cancer Genome Atlas and the Gene Expression Omnibus miRNA dataset, miR-92b and miR-99a were found with concordant directionality, up-regulated and down-regulated, respectively. In The Cancer Genome Atlas survival data, patients with the high level of miR-99b had obviously shorter overall survival time ( P=0.038). However, the level of miR-99a was not found to be significant. The 17 shared target genes of miR-92b were identified, such as DAB21IP, BCL21L11, SPHK2, PER2, and TSC1. The related pathways included positive regulation of transcription, positive regulation of cellular biosynthetic process, regulation of programmed cell death, etc. Conclusion: miR-92b was up-regulated in cholangiocarcinoma compared with normal controls. The high level of miR-92b was associated with adverse outcomes in cholangiocarcinoma patients, which might be partly explained by the targeted genes of miR-92b and their signaling pathways.

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Potential prognostic impact of EBV RNA‐seq reads in gastric cancer: a reanalysis of The Cancer Genome Atlas cohort

FEBS Open Bio ◽

10.1002/2211-5463.12803 ◽

2020 ◽

Vol 10 (3) ◽

pp. 455-467 ◽

Cited By ~ 1

Author(s):

Daichi Sadato ◽

Mina Ogawa ◽

Chizuko Hirama ◽

Tsunekazu Hishima ◽

Shin‐Ichiro Horiguchi ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Prognostic Impact ◽

Rna Seq ◽

Cancer Genome Atlas ◽

Genome Atlas

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Survival Outcomes by TP53 Mutation Status in Metastatic Breast Cancer

JCO Precision Oncology ◽

10.1200/po.17.00245 ◽

2018 ◽

pp. 1-15 ◽

Cited By ~ 6

Author(s):

Funda Meric-Bernstam ◽

Xiaofeng Zheng ◽

Maryam Shariati ◽

Senthil Damodaran ◽

Chetna Wathoo ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Metastatic Breast ◽

The Cancer Genome Atlas ◽

Survival Outcomes ◽

Tumor Subtype ◽

Free Survival ◽

Tp53 Mutations ◽

Cancer Genome Atlas ◽

Genome Atlas

Purpose To determine the significant genomic alterations in patients with metastatic breast cancer (MBC) and survival outcomes in common genotypes. Patients and Methods High-depth next-generation sequencing was performed for 202 genes in tumor and normal DNA from 257 patients with MBC, including 165 with estrogen receptor/progesterone receptor–positive and human epidermal growth factor receptor 2 (HER2 [hormone receptor positive (HR+)])–positive, 32 with HER2-positive, and 60 with triple-negative (estrogen receptor/progesterone receptor–negative and HER2-negative) disease. Kaplan-Meier survival analysis was performed in the discovery set, in patients with breast cancer analyzed in The Cancer Genome Atlas, and in a separate cohort of 98 patients with MBC who underwent clinical genomic testing. Results Significantly mutated genes (SMGs) varied by histology and tumor subtype, but TP53 was an SMG in all three subtypes. The most SMGs in patients with HR+ cancer were PIK3CA (32%), TP53 (29%), GATA3 (15%), CDH1 (8%), MAP3K1 (8%), PTEN (5%), TGFBR2 (4%), AKT1 (4%), and MAP2K4 (4%). TP53 mutations were associated with shorter recurrence-free survival ( P = .004), progression-free survival ( P < .001), and overall survival ( P = .003). Furthermore, TP53 status was prognostic among patients with HR+ cancer with PIK3CA mutations. TP53 mutations were associated with poorer overall survival in the 442 patients with HR+ breast cancer analyzed in The Cancer Genome Atlas ( P = .042) and in an independent set of 96 patients with HR+ MBC who underwent clinical sequencing ( P < .001). Conclusion SMGs differ by tumor subtype, but TP53 is significantly mutated in all three breast cancer subtypes. TP53 mutations are associated with poor prognosis in HR+ breast cancer and should be considered in the design and interpretation of precision oncology trials.

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