Dynamic Interplay between Structural Variations and 3D Genome Organization in Pancreatic Cancer

Du, Yongxing; Gu, Zongting; Li, Zongze; Yuan, Zan; Zhao, Yue; Zheng, Xiaohao; Bo, Xiaochen; Chen, Hebing; Wang, Chengfeng

doi:10.1002/advs.202200818

Cited by 19 publications

(15 citation statements)

References 84 publications

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“…RNA-seq was performed by the Annoroad Gene Company (Beijing, China) using the Illumina HiSeq X-ten system. For more detailed information, please refer to the Methods section of our previous work (Du et al 2022 ).…”

Section: Methodsmentioning

confidence: 99%

RETRACTED ARTICLE: ITGA3 acts as a purity-independent biomarker of both immunotherapy and chemotherapy resistance in pancreatic cancer: bioinformatics and experimental analysis

Zheng

et al. 2023

Funct Integr Genomics

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Contribution of integrin superfamily genes to treatment resistance remains uncertain. Genome patterns of thirty integrin superfamily genes were analyzed of using bulk and single-cell RNA sequencing, mutation, copy number, methylation, clinical information, immune cell infiltration, and drug sensitivity data. To select the integrins that are most strongly associated with treatment resistance in pancreatic cancer, a purity-independent RNA regulation network including integrins were constructed using machine learning. The integrin superfamily genes exhibit extensive dysregulated expression, genome alterations, epigenetic modifications, immune cell infiltration, and drug sensitivity, as evidenced by multi-omics data. However, their heterogeneity varies among different cancers. After constructing a three-gene (TMEM80, EIF4EBP1, and ITGA3) purity-independent Cox regression model using machine learning, ITGA3 was identified as a critical integrin subunit gene in pancreatic cancer. ITGA3 is involved in the molecular transformation from the classical to the basal subtype in pancreatic cancer. Elevated ITGA3 expression correlated with a malignant phenotype characterized by higher PD-L1 expression and reduced CD8+ T cell infiltration, resulting in unfavorable outcomes in patients receiving either chemotherapy or immunotherapy. Our findings suggest that ITGA3 is an important integrin in pancreatic cancer, contributing to chemotherapy resistance and immune checkpoint blockade therapy resistance. Graphical abstract

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Section: Methodsmentioning

confidence: 99%

RETRACTED ARTICLE: ITGA3 acts as a purity-independent biomarker of both immunotherapy and chemotherapy resistance in pancreatic cancer: bioinformatics and experimental analysis

Zheng

et al. 2023

Funct Integr Genomics

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“…SVs generally refer to genetic variants that are larger than 50 base pairs, such as insertions, deletions, inversions, translocations, duplications/amplifications, and chromosomal additions and deletions, as well as chromosomal rearrangements. 5,[102][103][104][105][106][107][108][109] Among them, chromosomal rearrangement is the most complex (such as chromothripsis and chromoplexy), which is a prominent feature of tumors and plays a crucial role in the occurrence and immune recognition of various malignant tumors. [110][111][112] Chromosomal rearrangements are not easily detected by traditional DNA sequencing techniques but can be screened by WES methods like mate pair sequencing (MPseq).…”

Section: The Source Of Neoantigensmentioning

confidence: 99%

Neoantigens: promising targets for cancer therapy

Xie

Shen

Gao

et al. 2023

Sig Transduct Target Ther

248

150

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Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies, including cancer vaccines, adoptive cell therapy and antibody-based therapies, especially for solid tumors. Neoantigens are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations, such as genomic mutation, dysregulated RNA splicing, disordered post-translational modification, and integrated viral open reading frames. Neoantigens are recognized as non-self and trigger an immune response that is not subject to central and peripheral tolerance. The quick identification and prediction of tumor-specific neoantigens have been made possible by the advanced development of next-generation sequencing and bioinformatic technologies. Compared to tumor-associated antigens, the highly immunogenic and tumor-specific neoantigens provide emerging targets for personalized cancer immunotherapies, and serve as prospective predictors for tumor survival prognosis and immune checkpoint blockade responses. The development of cancer therapies will be aided by understanding the mechanism underlying neoantigen-induced anti-tumor immune response and by streamlining the process of neoantigen-based immunotherapies. This review provides an overview on the identification and characterization of neoantigens and outlines the clinical applications of prospective immunotherapeutic strategies based on neoantigens. We also explore their current status, inherent challenges, and clinical translation potential.

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“…Deletions in the boundary regions of the two TADs result in their fusion. In the fused TADs, the MIR31HG promoter is abnormally regulated by the enhancer, leading to increased expression levels 299 …”

Section: D Genome Structural Variations and Diseasementioning

confidence: 99%

Three‐dimensional genome structure and function

Líu

Tsai

Yang

et al. 2023

MedComm

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Linear DNA undergoes a series of compression and folding events, forming various three‐dimensional (3D) structural units in mammalian cells, including chromosomal territory, compartment, topologically associating domain, and chromatin loop. These structures play crucial roles in regulating gene expression, cell differentiation, and disease progression. Deciphering the principles underlying 3D genome folding and the molecular mechanisms governing cell fate determination remains a challenge. With advancements in high‐throughput sequencing and imaging techniques, the hierarchical organization and functional roles of higher‐order chromatin structures have been gradually illuminated. This review systematically discussed the structural hierarchy of the 3D genome, the effects and mechanisms of cis‐regulatory elements interaction in the 3D genome for regulating spatiotemporally specific gene expression, the roles and mechanisms of dynamic changes in 3D chromatin conformation during embryonic development, and the pathological mechanisms of diseases such as congenital developmental abnormalities and cancer, which are attributed to alterations in 3D genome organization and aberrations in key structural proteins. Finally, prospects were made for the research about 3D genome structure, function, and genetic intervention, and the roles in disease development, prevention, and treatment, which may offer some clues for precise diagnosis and treatment of related diseases.

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Dynamic Interplay between Structural Variations and 3D Genome Organization in Pancreatic Cancer

Cited by 19 publications

References 84 publications

RETRACTED ARTICLE: ITGA3 acts as a purity-independent biomarker of both immunotherapy and chemotherapy resistance in pancreatic cancer: bioinformatics and experimental analysis

RETRACTED ARTICLE: ITGA3 acts as a purity-independent biomarker of both immunotherapy and chemotherapy resistance in pancreatic cancer: bioinformatics and experimental analysis

Neoantigens: promising targets for cancer therapy

Three‐dimensional genome structure and function

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