Identification of hallmarks of lung adenocarcinoma prognosis using whole genome sequencing

Liu, Li; Huang, Jiao; Wang, Ke; Li, Li; Li, Yangkai; Yuan, Jingsong; Wei, Sheng

doi:10.18632/oncotarget.5697

Cited by 9 publications

(10 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(Table)). Similar medium-to-large scale studies have identified mutation in BRD-containing proteins in hepatocellular carcinoma (HCC) 128 , squamous cell lung cancers 129 , lung adenocarcinomas [130][131][132] , small 133 and non-small cell lung cancers 134,135 , adenoid cystic carcinoma 136 , spinal ependymomas 137 , T-cell lymphoma 138 , thymic epithelial tumours 139 , cervical carcinomas 140 , endometrial carcinomas 141 , follicular lymphomas 142 , oesophageal squamous cell carcinomas [143][144][145] , colorectal (CRC) and gastric cancers 146 . However, no systematic studies focusing on the mutation load found on the actual BRD modules themselves exist and as such the contribution of Kac readout to the phenotypes observed remains elusive.…”

Section: Brd-containing Proteins In Cancermentioning

confidence: 99%

Functions of bromodomain-containing proteins and their roles in homeostasis and cancer

Fujisawa

Filippakopoulos

2017

Nat Rev Mol Cell Biol

475

473

View full text Add to dashboard Cite

Bromodomains (BRDs) are evolutionarily conserved protein-protein interaction modules that are found in a wide range of proteins with diverse catalytic and scaffolding functions and are present in most tissues. BRDs selectively recognize and bind to acetylated Lys residues - particularly in histones - and thereby have important roles in the regulation of gene expression. BRD-containing proteins are frequently dysregulated in cancer, they participate in gene fusions that generate diverse, frequently oncogenic proteins, and many cancer-causing mutations have been mapped to the BRDs themselves. Importantly, BRDs can be targeted by small-molecule inhibitors, which has stimulated many translational research projects that seek to attenuate the aberrant functions of BRD-containing proteins in disease.

show abstract

Section: Brd-containing Proteins In Cancermentioning

confidence: 99%

Functions of bromodomain-containing proteins and their roles in homeostasis and cancer

Fujisawa

Filippakopoulos

2017

Nat Rev Mol Cell Biol

475

473

View full text Add to dashboard Cite

show abstract

“…Sriram et al [14] found that the drop of copy number and decreased expression of SOCS6 were carefully bound up with the recurrence of LUSC. Liu et al [15] found that CNV of TERT with PBX1P1 was related to the development of LUAD. CNV-driven FRGs have rarely been reported in LUAD.…”

Section: Introductionmentioning

confidence: 99%

Construction and Validation of a CNV-Driven Ferroptosis-Related Gene Signature for Predicting the Prognosis of Lung Adenocarcinoma

Wang

et al. 2022

Journal of Sensors

View full text Add to dashboard Cite

Background. Previous studies have shown that ferroptosis plays an integral role in the development of cancer and copy number variations (CNVs) have been reported to associated with the ferroptosis. However, the role of CNVs-driven ferroptosis-related genes (FRGs) in lung adenocarcinoma (LUAD) continues to be poorly understood. Therefore, we aimed to establish a novel gene signature in LUAD based on CNVs-driven ferroptosis-related genes. Methods. The transcriptome data and clinical features of LUAD patients were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. Differential analysis was carried out to recognize differentially expressed CNV-driven FRGs. Univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were utilized to identify prognosis-associated genes. Kaplan-Meier (K-M) analysis was a builder to estimate the worth of model. In addition, the nomogram was created to estimate survival probability of each patient. Ultimately, the immune microenvironment landscape between high and low risk groups was evaluated. Results. A total of 22 differentially expressed CNV-driven FRGs were acquired in LUAD. These genes were significantly associated with serine family amino acid metabolism, iron regulation, reactive oxygen species metabolism, and cellular response to oxidative stress, and were involved in amino acid metabolism, malaria, amino acid biosynthesis, and HIF-1 signaling pathways. Moreover, on the strength of 6 genes (TFAP2A, SLC2A1, AURKA, CDO1, SLC7A11, and ALOX5), the prognostic model was created, and the LUAD samples were significantly fall into the high- and low-risk groups, with the high-risk group had a poorer prognosis. Furthermore, risk score was an independent prognostic element. The nomogram with excellent predictive performance was developed for calculating the final result of LUAD patients at 1, 2, and 3 years. Finally, 19 immune cells had different infiltration differences among groups. Conclusion. A novel CNV-driven ferroptosis-related prognosis was established and could be used as a predictive indicator in LUAD. However, further clinical and in vivo in vitro experiments are necessary.

show abstract

“…SDHA is a tumor suppressor and is implicated in paraganglioma and gastrointestinal stromal tumors [14]. While association of SDHA copy number variation to prognosis was found in lung squamous cell carcinoma [15], we have found no literature exploring the connection of SDHA to lung adenocarcinoma.…”

Section: Resultsmentioning

confidence: 92%

Development of somatic mutation signatures for risk stratification and prognosis in lung and colorectal adenocarcinomas

et al. 2019

View full text Add to dashboard Cite

BackgroundPrognostic signatures are vital to precision medicine. However, development of somatic mutation prognostic signatures for cancers remains a challenge. In this study we developed a novel method for discovering somatic mutation based prognostic signatures.ResultsSomatic mutation and clinical data for lung adenocarcinoma (LUAD) and colorectal adenocarcinoma (COAD) from The Cancer Genome Atlas (TCGA) were randomly divided into training (n = 328 for LUAD and 286 for COAD) and validation (n = 167 for LUAD and 141 for COAD) datasets. A novel method of using the log2 ratio of the tumor mutation frequency to the paired normal mutation frequency is computed for each patient and missense mutation. The missense mutation ratios were mean aggregated into gene-level somatic mutation profiles. The somatic mutations were assessed using univariate Cox analysis on the LUAD and COAD training sets separately. Stepwise multivariate Cox analysis resulted in a final gene prognostic signature for LUAD and COAD. Performance was compared to gene prognostic signatures generated using the same pipeline but with different somatic mutation profile representations based on tumor mutation frequency, binary calls, and gene-gene network normalization. Signature high-risk LUAD and COAD cases had worse overall survival compared to the signature low-risk cases in the validation set (log-rank test p-value = 0.0101 for LUAD and 0.0314 for COAD) using mutation tumor frequency ratio (MFR) profiles, while all other methods, including gene-gene network normalization, have statistically insignificant stratification (log-rank test p-value ≥0.05). Most of the genes in the final gene signatures using MFR profiles are cancer-related based on network and literature analysis.ConclusionsWe demonstrated the robustness of MFR profiles and its potential to be a powerful prognostic tool in cancer. The results are robust according to validation testing and the selected genes are biologically relevant.

show abstract

Identification of hallmarks of lung adenocarcinoma prognosis using whole genome sequencing

Cited by 9 publications

References 42 publications

Functions of bromodomain-containing proteins and their roles in homeostasis and cancer

Functions of bromodomain-containing proteins and their roles in homeostasis and cancer

Construction and Validation of a CNV-Driven Ferroptosis-Related Gene Signature for Predicting the Prognosis of Lung Adenocarcinoma

Development of somatic mutation signatures for risk stratification and prognosis in lung and colorectal adenocarcinomas

Contact Info

Product

Resources

About