Real-world large-scale study of <i>ERBB2</i> gene fusions and its response to afatinib in Chinese non-small cell lung cancer (NSCLC): A multicenter study.

Xu, C.; Wang, Wen xian; Zhang, Qu-Xia; Chen, Yu; Fang, Yong; Zhu, You‐cai; Huang, Yun-jian; Wang, Hong; Zhuang, Wei; Zhang, Yinbin; Wang, Liping; Cai, Shangli; Huang, Jian; Feng, Shuitu; Fang, M.; Chen, Gang; Lv, Tangfeng; Song, Yong

doi:10.1200/jco.2019.37.15_suppl.e13002

Cited by 3 publications

(2 citation statements)

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“…A subset of the 11 gene signature has recently been reported in the context of lung cancer, either as an oncogenic driver (e.g. CD79B [ 32 ]) or a prognostic marker (e.g. TRAF3IP3, SKAP2, and SS18L2 ) [ 33 – 35 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular signature comprising 11 platelet-genes enables accurate blood-based diagnosis of NSCLC

et al. 2020

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Background Early diagnosis is crucial for effective medical management of cancer patients. Tissue biopsy has been widely used for cancer diagnosis, but its invasive nature limits its application, especially when repeated biopsies are needed. Over the past few years, genomic explorations have led to the discovery of various blood-based biomarkers. Tumor Educated Platelets (TEPs) have, of late, generated considerable interest due to their ability to infer tumor existence and subtype accurately. So far, a majority of the studies involving TEPs have offered marker-panels consisting of several hundreds of genes. Profiling large numbers of genes incur a significant cost, impeding its diagnostic adoption. As such, it is important to construct minimalistic molecular signatures comprising a small number of genes. Results To address the aforesaid challenges, we analyzed publicly available TEP expression profiles and identified a panel of 11 platelet-genes that reliably discriminates between cancer and healthy samples. To validate its efficacy, we chose non-small cell lung cancer (NSCLC), the most prevalent type of lung malignancy. When applied to platelet-gene expression data from a published study, our machine learning model could accurately discriminate between non-metastatic NSCLC cases and healthy samples. We further experimentally validated the panel on an in-house cohort of metastatic NSCLC patients and healthy controls via real-time quantitative Polymerase Chain Reaction (RT-qPCR) (AUC = 0.97). Model performance was boosted significantly after artificial data-augmentation using the EigenSample method (AUC = 0.99). Lastly, we demonstrated the cancer-specificity of the proposed gene-panel by benchmarking it on platelet transcriptomes from patients with Myocardial Infarction (MI). Conclusion We demonstrated an end-to-end bioinformatic plus experimental workflow for identifying a minimal set of TEP associated marker-genes that are predictive of the existence of cancers. We also discussed a strategy for boosting the predictive model performance by artificial augmentation of gene expression data.

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Section: Discussionmentioning

confidence: 99%

Molecular signature comprising 11 platelet-genes enables accurate blood-based diagnosis of NSCLC

et al. 2020

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“… 18 The frequency of HER2 overexpression also varies between populations (7.7%–23%; 15.4% in Chinese). 19 In addition, HER2 fusions (0.29%) 20 and tyrosine kinase domain duplication (KDD) (0.01%) are also observed in Chinese, which may benefit from HER2 inhibitors. 21 It has been well documented that HER2 amplification is poorly correlated with HER2 overexpression in NSCLC.…”

Section: Her2 Alterations and Their Mechanisms Of Pathogenesismentioning

confidence: 99%

Chinese expert consensus on the diagnosis and treatment of HER2‐altered non–small cell lung cancer

Zhang

Wang

et al. 2022

Thoracic Cancer

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Human epidermal growth factor receptor 2 (HER2) possesses tyrosine kinase activity and participates in cell growth, differentiation and migration, and survival. Its alterations, mainly including mutations, amplifications, and overexpression are associated with poor prognosis and are one of the major drivers in non–small cell lung cancer (NSCLC). Several clinical trials had been investigating on the treatments of HER2‐altered NSCLC, including conventional chemotherapy, programmed death 1 (PD‐1) inhibitors, tyrosine kinase inhibitors (TKIs) and antibody‐drug conjugates (ADCs), however, the results were either disappointing or encouraging, but inconsistent. Trastuzumab deruxtecan (T‐DXd) was recently approved by the Food and Drug Administration as the first targeted agent for treating HER2 ‐mutant NSCLC. Effective screening of patients is the key to the clinical application of HER2‐targeted agents such as TKIs and ADCs. Various testing methods are nowadays available, including polymerase chain reaction (PCR), next‐generation sequencing (NGS), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), etc. Each method has its pros and cons and should be reasonably assigned to appropriate patients for diagnosis and guiding treatment decisions. To help standardize the clinical workflow, our expert group reached a consensus on the clinical management of HER2‐altered NSCLC, focusing on the diagnosis and treatment strategies.

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Prognostic value of structural variants in early breast cancer patients

Kim,

Park,

Park

et al. 2024

npj Breast Cancer

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Genomic analysis of structural variants(SVs) in breast cancer (BC) patients has been conducted, but the relationship between genomic alterations and BC prognosis remains unclear. We performed RNA sequencing of 297 early BC fresh-frozen tissues. We identified SVs using three tools (STAR.Arriba, STAR.fusion, and STAR.SEQR) with the COSMIC and Mitelman databases as guide references. We found a median of five to eight fusions per sample. In BC intrinsic subtypes, normal subtype had the fewest fusions (median: 1, interquartile range [IQR]: 0, 3) followed by luminal A (median: 5.5, IQR: 2.75, 10.25), luminal B (median: 9, IQR: 6, 16.5), HER2-enriched (median: 9, IQR: 6, 16.5) and basal (median 10, IQR: 6, 15.5) subtypes (p < 0.05). Intrachromosomal fusion was more frequent observed rather than interchromosomal fusion. In location, chromosome 17 had the most fusions followed by chromosome 1 and 11. When samples were divided into high and low fusion groups based on a cut-off value of 11 fusions, five-year event-free survival (5Y-EFS) was 68.1% in the high fusion group (n = 72) and 80.1% in the low fusion group (n = 125) (p = 0.024) while 75.6% among all patients (95% confidence interval: 0.699, 0.819). Among BC subtype, TNBCs with more fusions had shorter EFS compared to those with fewer fusions (5Y-EFS rate: 65.1% vs. 85.7%; p = 0.013) but no EFS differences were observed in other BC subtypes. ESTIMATE ImmuneScore was also associated with the number of fusions in TNBC (p < 0.005) and TNBCs with high ImmuneScore had better 5Y-EFS compared to those with low ImmuneScore (p = 0.041). In conclusion, diverse fusions were observed by BC subtype, and the number of fusions was associated with BC survival outcome and immune status in TNBC.

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Real-world large-scale study of ERBB2 gene fusions and its response to afatinib in Chinese non-small cell lung cancer (NSCLC): A multicenter study.

Cited by 3 publications

References 0 publications

Molecular signature comprising 11 platelet-genes enables accurate blood-based diagnosis of NSCLC

Molecular signature comprising 11 platelet-genes enables accurate blood-based diagnosis of NSCLC

Chinese expert consensus on the diagnosis and treatment of HER2‐altered non–small cell lung cancer

Prognostic value of structural variants in early breast cancer patients

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