Article
Cell Biology
Jisun Lim, Yeon Bi Han, Soo Young Park, Soyeon Ahn, Hyojin Kim, Hyun Jung Kwon, Choon-Taek Lee, Sukki Cho, Jin-Haeng Chung
Summary: The study identified gene expression patterns and immune tumor microenvironment behaviors in the continuum from atypical adenomatous hyperplasia (AAH) to lung adenocarcinoma (ADC). Up-regulated genes with stepwise change of expression from AAH to ADC were found, as well as differences in immune cell profiles between AAH and ADC. The differential expression during ADC development was found to potentially affect immune function in synchronous precursors and tumor lesions in patients with lung cancer.
Article
Medicine, General & Internal
Hui Zeng, Ying Wang, Ying Wang, Yongjun Zhang
Summary: The methylation level of XXYLT1 gene is significantly higher in lung adenocarcinoma tissues compared to para-carcinoma and normal lung tissues, while the mRNA expression of XXYLT1 is significantly lower. This difference is particularly significant in male patients.
Article
Multidisciplinary Sciences
Kaja Kostyrko, Marta Roman, Alex G. Lee, David R. Simpson, Phuong T. Dinh, Stanley G. Leung, Kieren D. Marini, Marcus R. Kelly, Joshua Broyde, Andrea Califano, Peter K. Jackson, E. Alejandro Sweet-Cordero
Summary: In this study, researchers used RNAi screens to identify UHRF1 as an epigenetic regulator that is specifically vulnerable in KRAS mutant lung cancer cells. Knocking out UHRF1 selectively impaired the growth and induced apoptosis in KRAS mutant cells by causing global DNA hypomethylation and upregulation of tumor suppressor genes. In vivo experiments showed that UHRF1 knock-out inhibits tumor growth in KRAS-driven mouse lung cancer models. High UHRF1 expression in lung cancer patients is associated with low TSG expression and predicts worse outcomes in KRAS mutant tumors. These findings suggest that UHRF1 could be a potential target for therapeutic intervention in KRAS-driven cancer.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Quanyou Wu, Lin Feng, Yaru Wang, Yousheng Mao, Xuebing Di, Kaitai Zhang, Shujun Cheng, Ting Xiao
Summary: Alternative RNA splicing is a crucial mechanism in posttranscriptional gene regulation that contributes to protein diversity. In this study, we investigated the aberrant alternative splicing events in lung adenocarcinoma (LUAD) and their biological and clinical implications using multi-omics data. We identified 3688 aberrant alternative splicing events in LUAD, mainly involving alternative promoter and exon skip. Our findings demonstrated the regulatory roles of RNA binding proteins, somatic mutations, and DNA methylations on alternative splicing. We also identified a subtype of LUAD with a specific alternative splicing pattern that was associated with better prognosis and response to immunotherapy. These findings provide insights into tumorigenesis and tumor immune microenvironment, and have implications for the development of splice-switching therapies for LUAD.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Article
Pathology
Alain C. Borczuk
Summary: Pathologic evaluation of lung adenocarcinoma has become more complex due to a better understanding of disease progression and prognosis. Different histologic growth patterns reflect varying degrees of aggressiveness in the disease, leading to the need for clearer morphologic groups for grading. The progression of adenocarcinoma from preserving alveolar architecture to remodeling lung structure has introduced criteria for invasive growth rather than in-situ growth.
Article
Endocrinology & Metabolism
Wen Wang, Hao Bo, Yumei Liang, Guoli Li
Summary: This study demonstrates that DNA copy number amplification and hypomethylation are positively correlated with LINC00467 expression in LUAD. Moreover, DNA copy number amplification is significantly associated with distant metastasis, immune infiltration, and poor survival in LUAD. Knockdown of LINC00467 affects the expression of a panel of microRNAs in LUAD cells, which in turn impacts the target genes involved in multiple biological processes. In addition, a ceRNA network specific to LINC00467 in LUAD, consisting of two microRNAs and five mRNAs, suggests that BARX2 and BCL9 may serve as potential prognostic biomarkers for LUAD patients.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Genetics & Heredity
Yifan Chen, Shanwu Ma, Chutong Lin, Zhipeng Zhu, Jie Bai, Zhongnan Yin, Yan Sun, Fengbiao Mao, Lixiang Xue, Shaohua Ma
Summary: This study identified seven novel methylation markers from cfDNA methylation data that are associated with lung adenocarcinoma risk. These markers can be used to classify different prognostic subgroups and are significantly associated with overall survival in lung adenocarcinoma patients. The reliability of these markers was further validated.
FRONTIERS IN GENETICS
(2023)
Article
Respiratory System
Duoduo Xu, Cheng Li, Youjing Zhang, Jizhou Zhang
Summary: This study constructed a prognostic model for predicting the prognosis of LUAD patients, by analyzing DNA methylation differences to identify potential biomarkers. The results showed that specific methylation sites were associated with patient prognosis.
BMC PULMONARY MEDICINE
(2022)
Article
Genetics & Heredity
Wenhan Cai, Miao Jing, Jiaxin Wen, Hua Guo, Zhiqiang Xue
Summary: This study focused on the epigenetic alterations of DNA methylation and miRNAs in lung adenocarcinoma (LUAD). The study identified differentially expressed genes associated with these epigenetic changes in LUAD and identified potential small-molecule drugs and therapeutic targets for LUAD treatment.
FRONTIERS IN GENETICS
(2022)
Article
Oncology
Xuewei Hao, Jun Zhang, Guoyou Chen, Weiwei Cao, Hongyang Chen, Shuo Chen
Summary: This study demonstrates that low expression of GSTM5 and its high DNA methylation status may serve as a novel potential molecular target gene for lung adenocarcinoma (LUAD).
Article
Oncology
Xuelong Wang, Bin Zhou, Yuxin Xia, Jianxin Zuo, Yanchao Liu, Xin Bi, Xiong Luo, Chengwei Zhang
Summary: This study established a robust three-DMSs signature for predicting overall survival in LUAD patients, and developed a methylation-based nomogram for guiding personalized treatment. The nomogram showed good performance in both TCGA-LUAD and GSE56044 cohorts, providing a clinically available guide for LUAD patients.
Article
Oncology
Anna Diacofotaki, Axelle Loriot, Charles De Smet
Summary: This study reveals the impact of DNA hypomethylation on the tumor transcriptome and identifies aberrant activation of cell-type specific gene clusters in hypomethylated tumors.
Article
Pharmacology & Pharmacy
Yamin Jie, Jianing Wu, Dongxue An, Man Li, Hongjiang He, Duo Wang, Anxin Gu, E. Mingyan
Summary: This study characterized the molecular features of lung adenocarcinoma (LUAD) patients based on tumor microenvironment (TME)-related signatures. Four TME-based molecular subtypes were identified, and their overall survival, genomic characteristics, DNA methylation pattern, immune microenvironment, and biological pathways were analyzed. A TME-related risk model was constructed, which showed clinical value in predicting LUAD prognosis and guiding immunotherapy.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Yilin Yu, Zhiping Wang, Qunhao Zheng, Jiancheng Li
Summary: GREB1L expression is significantly increased in LUAD and correlated with poor prognosis. High GREB1L expression is associated with enrichment in cell cycle, immune regulation, and methylation, making it a potential molecular marker for LUAD.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Hong Gao, Jun Yang, Lu He, Wei Wang, Yanhong Liu, Yue Hu, Meiling Ge, Jie Ding, Qing Ye
Summary: The combined promoter methylation assay for SHOX2 and RASSF1A can be used for screening and diagnosis of early LUAD, with good sensitivity and specificity. The promoter methylation levels of SHOX2 and RASSF1A were associated with their abnormal mRNA expression, and affected DNA instability, cell proliferation, apoptosis, and tumor microenvironment in patients with LUAD.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Mark J. Schliekelman, Ayumu Taguchi, Jun Zhu, Xudong Dai, Jaime Rodriguez, Muge Celiktas, Qing Zhang, Alice Chin, Chee-Hong Wong, Hong Wang, Lisa McFerrin, Suhaida A. Selamat, Chenchen Yang, Evan M. Kroh, Kavita S. Garg, Carmen Behrens, Adi F. Gazdar, Ite A. Laird-Offringa, Muneesh Tewari, Ignacio I. Wistuba, Jean P. Thiery, Samir M. Hanash
Article
Biochemistry & Molecular Biology
Suhaida A. Selamat, Brian S. Chung, Luc Girard, Wei Zhang, Ying Zhang, Mihaela Campan, Kimberly D. Siegmund, Michael N. Koss, Jeffrey A. Hagen, Wan L. Lam, Stephen Lam, Adi F. Gazdar, Ite A. Laird-Offringa
Article
Oncology
Kit W. Tam, Wei Zhang, Junichi Soh, Victor Stastny, Min Chen, Han Sun, Kelsie Thu, Jonathan J. Rios, Chenchen Yang, Crystal N. Marconett, Suhaida. A. Selamat, Ite A. Laird-Offringa, Ayumu Taguchi, Samir Hanash, David Shames, Xiaotu Ma, Michael Q. Zhang, Wan L. Lam, Adi Gazdar
JOURNAL OF THORACIC ONCOLOGY
(2013)
Article
Biochemistry & Molecular Biology
I. M. Wilson, E. A. Vucic, K. S. S. Enfield, K. L. Thu, Y. A. Zhang, R. Chari, W. W. Lockwood, N. Radulovich, D. T. Starczynowski, J. P. Banath, M. Zhang, A. Pusic, M. Fuller, K. M. Lonergan, D. Rowbotham, J. Yee, J. C. English, T. P. H. Buys, S. A. Selamat, I. A. Laird-Offringa, P. Liu, M. Anderson, M. You, M. S. Tsao, C. J. Brown, K. L. Bennewith, C. E. MacAulay, A. Karsan, A. F. Gazdar, S. Lam, W. L. Lam
Article
Genetics & Heredity
Crystal N. Marconett, Beiyun Zhou, Megan E. Rieger, Suhaida A. Selamat, Mickael Dubourd, Xiaohui Fang, Sean K. Lynch, Theresa Ryan Stueve, Kimberly D. Siegmund, Benjamin P. Berman, Zea Borok, Ite A. Laird-Offringa
Article
Oncology
E. Thirthagiri, S. Y. Lee, P. Kang, D. S. Lee, G. T. Toh, S. Selamat, S-Y Yoon, N. A. Mohd Taib, M. K. Thong, C. H. Yip, S. H. Teo
BREAST CANCER RESEARCH
(2008)