Genomic alterations and evolution of cell clusters in metastatic invasive micropapillary carcinoma of the breast

Shi, Qianqian; Shao, Kwang‐Tsao; Jia, Hongqin; Cao, Boyang; Li, Weidong; Dong, Shuping; Liu, Jian; K, Wu; Liu, Meng; Liu, Fangfang; Zhou, Hanlin; Lv, Junqiang; Gu, Feng; Li, Luyuan; Zhu, Shida; Li, Shuai; Li, Guibo; Fu, Li

doi:10.1038/s41467-021-27794-4

Cited by 20 publications

(17 citation statements)

References 60 publications

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“…The intratumoral heterogeneity (ITH) patterns of the paired components in each sample were quantified to estimate the component’s genetic correlations. As expected, the MPP component had higher ITH levels compared with those of the non-MPP component, consistent with the aggressive profile of the MPP component, suggesting an expansionary predominance of this component in early progression [ 19 , 20 ] ( Figure 1 I), as reported previously [ 21 , 22 ]. These results suggest that, although there is some homology between MPP and non-MPP components, both emerged and retained their respective adaptive mutations during their development, with a more complex genomic landscape in the MPP region relative to the other components.…”

Section: Resultssupporting

confidence: 89%

Whole-Exome Sequencing Reveals the Genomic Features of the Micropapillary Component in Ground-Glass Opacities

Meng

Zhang

Wang

et al. 2022

Cancers

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Background: Micropapillary components are observed in a considerable proportion of ground-glass opacities (GGOs) and contribute to the poor prognosis of patients with invasive lung adenocarcinoma (LUAD). However, the underlying mutational processes related to the presence of micropapillary components remain obscure, limiting the development of clinical interventions. Methods: We collected 31 GGOs, which were separated into paired micropapillary and non-micropapillary components using microdissection. Whole-exome sequencing (WES) was performed on the GGO components, and bioinformatics analysis was conducted to reveal the genomic features of the micropapillary component in invasive LUAD. Results: The micropapillary component had more genomic variations, including tumor mutation burden, intratumoral heterogeneity, and copy number variation. We also observed the enrichment of AID/APOBEC mutation signatures and an increased activation of the RTK/Ras, Notch, and Wnt oncogenic pathways within the micropapillary component. A phylogenetic analysis further suggested that ERBB2/3/4, NCOR1/2, TP53, and ZNF469 contributed to the micropapillary component’s progression during the early invasion of LUAD, a finding that was validated in the TCGA cohort. Conclusions: Our results revealed specific mutational characteristics of the micropapillary component of invasive LUAD in an Asian population. These characteristics were associated with the formation of high-grade invasive patterns. These preliminary findings demonstrated the potential of targeting the micropapillary component in patients with early-stage LUAD.

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Section: Resultssupporting

confidence: 89%

Whole-Exome Sequencing Reveals the Genomic Features of the Micropapillary Component in Ground-Glass Opacities

Meng

Zhang

Wang

et al. 2022

Cancers

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“…Caso et al ( 17 ) employed targeted next-generation sequencing (NGS), and revealed that tumors in the high-risk group had higher copy number amplifications, as well as statistical significance alteration in three oncogenic pathways (p53, Wnt, Myc), compared with those in the intermediate or low-risk group. Whole-genome sequencing of tumor cell clusters from MIP in breast cancer shares high-frequency copy-number loss of PRDM16 and IGSF9 and the copy-number gain of ALDH2 ( 18 ). In addition to the genomic instability, non-genetic factors also contributed to the functional and phenotypic heterogeneity of histological pathology.…”

Section: Discussionmentioning

confidence: 99%

High‑risk pathological subtype associated FAM83A‑AS1 promotes malignancy and glycolysis of lung adenocarcinoma via miR‑202‑3p/HK2 axis

et al. 2023

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According to the diverse cellular morphology, lung adenocarcinoma (LUAD) was classified into five pathological subtypes, referred to as follows: High-risk group (micropapillary and solid), intermediate-risk group (acinar and papillary) and low-risk group (epidic). Nevertheless, little is known about the biological function of long non-coding RNA (lncRNA) in the molecular determination of LUAD histologic patterns. Screening the transcriptional expression data from TCGA-LUAD, the differentially expressed lncRNA across the divergent pathological subtypes were explored. Pan-cancer analysis revealed the characteristic of FAM83A-AS1, which was also confirmed in the LUAD tissues. The function of FAM83A-AS1 was uncovered through the in vitro assays. RNA immunoprecipitation and dual-luciferase reporter assays were performed to explore the molecular mechanisms of FAM83A-AS1. In the present study, it was identified that the expression of FAM83A-AS1 was increased from the low-risk group to the high, which was associated with a poorer prognosis and higher risk of recurrence. Pan-cancer analysis revealed that FAM83A-AS1 was positively correlated with high tumor mutational burden. Additionally, FAM83A-AS1 promoted cell migration, invasion and growth of LUAD cancer cells. Mechanistically, FAM83A-AS1 sponged miR-202-3p to regulate the expression of hexokinase II (HK2) in post-transcription, which facilitated the malignancy and glycolysis. The present study uncovered the biological roles of FAM83A-AS1/miR-202-3p/HK2 axis in regulating malignancy and glycolysis of LUAD, which provided novel avenues to addressing the determination of histologic patterns.

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“…Screening for differentially expressed proteins in coronary artery disease congenital cold syndrome based on tandem mass-labeling techniques revealed upregulated expression of IGLV4-69 [42] . IGSF9 is active in axons and plasma membranes and plays a role upstream of dendrite development or in the regulation of dendrite organization [43] . IGSF9 was found to be associated with the prognosis of nasopharyngeal carcinoma and that downregulation of IGSF9 expression reduced the proliferation, migration and invasion of nasopharyngeal carcinoma cells, and that hypoxia induced IGSF9 expression [44,45] .…”

Section: Discussionmentioning

confidence: 99%

Multi-gene models for survival prognosis of colorectal cancer patients

Zhang

et al. 2022

Preprint

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Background The lack of effective prognostic models for colorectal cancer (CRC) makes it crucial to establish a reliable prognostic model for colorectal cancer. The aim of this study was to develop a reliable prognostic model in CRC. Using CRC samples from the TCGA database, a multi-gene combination model was screened for prognosis in CRC patients and the prognostic power of the multi-gene combination model was validated. We screened a multi-gene combination model for risk stratification and prognosis of CRC patients, which is important for individualised clinical treatment and long-term management of colorectal cancer patients. Results To solve these questions, we used data from colorectal cancer patients in the TCGA database to uncover differential genes, screened variables using one-way COX analysis and LASSO regression analysis, and then screened for the polygenic combination most associated with colorectal cancer and assessed its significance on survival events using multi-factor COX analysis and ROC curves to assess polygenic combinations. Finally, using gene enrichment analysis, the polygenic combinations were found to be associated with tRNA biosynthesis, homologous recombination, nucleotide excision repair, ribosome biogenesis in eukaryotes and DNA replication. Conclusions The multi-gene combination (FCGBP, GSTM1, IGLV4-69, IGSF9 and PCOLCE2) model screened in this study is capable of prognosticating colorectal cancer, and the findings of this study could shed new light on the prognosis of colorectal cancer in the clinical setting.

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Genomic alterations and evolution of cell clusters in metastatic invasive micropapillary carcinoma of the breast

Cited by 20 publications

References 60 publications

Whole-Exome Sequencing Reveals the Genomic Features of the Micropapillary Component in Ground-Glass Opacities

Whole-Exome Sequencing Reveals the Genomic Features of the Micropapillary Component in Ground-Glass Opacities

High‑risk pathological subtype associated FAM83A‑AS1 promotes malignancy and glycolysis of lung adenocarcinoma via miR‑202‑3p/HK2 axis

Multi-gene models for survival prognosis of colorectal cancer patients

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