Development of a RNA-Seq Based Prognostic Signature in Lung Adenocarcinoma

Shukla, Sudhanshu; Evans, Joseph R.; Malik, Rohit; Feng, Felix Y.; Dhanasekaran, Saravana M.; Cao, Xuhong; Chen, Guoan; Beer, David G.; Jiang, Hui; Chinnaiyan, Arul M.

doi:10.1093/jnci/djw200

Cited by 170 publications

(180 citation statements)

References 45 publications

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“…The risk score was calculated as follows: risk score = (0.597* expression level of EMP3 + 0.825* expression level of GSX2 + 0.942* expression level of EMILIN3 ). Patients were divided into low-risk and high-risk groups according to their risk scores, and the cut-off value was set at 75 th percentile [20] (Fig. 3A).…”

Section: Resultsmentioning

confidence: 99%

Integrative Analysis of DNA Methylation and Gene Expression Identify a Three-Gene Signature for Predicting Prognosis in Lower-Grade Gliomas

Zeng

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: In the current study, we performed an integrated analysis of genome-wide methylation and gene expression data to find novel prognostic genes for lower-grade gliomas (LGGs). Methods: First, TCGA methylation data were used to identify prognostic genes associated with promoter methylation. Second, candidate genes that were stably regulated by promoter methylation were explored. Third, Cox proportional hazards regression analysis was used to generate a prognostic signature, and the signature genes were used to construct a survival risk score system. Results: Three genes (EMP3, GSX2 and EMILIN3) were selected as signature genes. These three signature genes were used to construct a survival risk score system. The high-risk group exhibited significantly worse overall survival (OS) and relapse-free survival (RFS) as compared to the low-risk group in the TCGA dataset. The association of the three-gene prognostic signature with patient’ survival was then validated using the CGGA dataset. Moreover, Kaplan-Meier plots showed that the three-gene prognostic signature risk remarkably stratified grade II and grade III patients in terms of both OS and RFS in the TCGA cohort. There was also a significant difference between the low- and high-risk groups in IDH wild-type glioma patients, indicating that the three-gene signature may be able to help in predicting prognosis for patients with IDH wild-type gliomas. Conclusion: We identified and validated a three-gene (EMP3, GSX2 and EMILIN3) prognostic signature in LGGs by integrating multidimensional genomic data from the TCGA and CGGA datasets, which may help in fine-tuning the current histology-based tumors classification system and providing better stratification for future clinical trials.

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Section: Resultsmentioning

confidence: 99%

Integrative Analysis of DNA Methylation and Gene Expression Identify a Three-Gene Signature for Predicting Prognosis in Lower-Grade Gliomas

Zeng

Liu

et al. 2018

Cell Physiol Biochem

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“…High levels of CD109 expression have been detected in various tumor‐cell lines and tumor tissues, including those associated with squamous cell carcinomas (SCCs) of the lung, esophagus, uterus, and oral cavity, adenocarcinomas of the lung and pancreas, breast cancer, glioblastoma, hepatocellular carcinoma, urothelial carcinoma of the urinary bladder, and several types of sarcomas (Table ) . Immunohistochemical (IHC) analyses revealed elevated CD109 expression on tumor cells (Fig.…”

Section: Cd109 Is a Membrane Protein Expressed In Malignant Tumorsmentioning

confidence: 99%

CD109: a multifunctional GPI‐anchored protein with key roles in tumor progression and physiological homeostasis

Mii

Enomoto

Shiraki

et al. 2019

Pathology International

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CD109 is a glycosylphosphatidylinositol‐anchored glycoprotein and a member of the α2‐macroglobulin/C3,C4,C5 family of thioester‐containing proteins first identified as being expressed on blood cells, including activated T cells and platelets, and a subset of CD34 + bone marrow cells containing megakaryocyte progenitors. Although CD109 carries the biallelic platelet‐specific alloantigen Gov, the physiological functions or roles of CD109 in human disease remain largely unknown. It was recently demonstrated that CD109 is expressed in many malignant tumors, including various squamous cell carcinomas and adenocarcinomas, and plays a role as a multifunctional coreceptor. CD109 reportedly associates with transforming growth factor (TGF)‐β receptors and negatively regulates TGF‐β signaling in keratinocytes. Additionally, CD109 is potentially related to signal transducer and activator of transcription‐3 signaling and aberrant cell proliferation. In this review, we describe recent evidence of CD109‐specific significance in malignant tumors shown in mouse models and human tissues. Furthermore, we discuss the physiological functions of CD109 in vitro and in vivo, including results of phenotype analyses of CD109‐deficient mice exhibiting epidermal hyperplasia and osteopenia.

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“…There has been much debate regarding the reproducibility of mRNA expression platforms (43,44) and besides technological limitations (e.g., fresh-frozen tissue vs. formalin-fixed paraffin-embedded samples), biases (22) and statistical approaches (45), several other reasons can be speculated for the lack of fully validated prognostic signatures in lung cancer. As lung cancer subtyping moves from histological to genomic classifications, the failure to validate signatures may be due to the need for different signatures according to clinically relevant groupings, for example, EGFR-mutated (46), KRAS-mutated (23), or now by immunophenotypes (24).…”

Section: Prognostic Multigene Signaturesmentioning

confidence: 99%

Prognostic and predictive biomarkers post curative intent therapy

Feldman¹,

Kim²

2017

Ann. Transl. Med.

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Large-scale screening trials have demonstrated that early diagnosis of lung cancer results in a significant reduction in lung cancer mortality. Despite improvements in detecting more lung cancers at early stages, the 5-year survival rates of lung cancers diagnosed before widespread disease is only 30-50%.High rates of recurrence, despite early diagnosis, suggest the need to improve treatment strategies based on the likelihood of recurrence in patient subsets, as well as explore the role of predictive markers for therapy selection in the adjuvant setting. In the era of personalized medicine, there have been a wide array of molecular alterations and signatures studied for their potential prognostic and predictive utility, however most have failed to translate into clinical tools. This review will discuss progress made in clinical management of lung cancer, and recent progress in the development of patient selection tools for the refinement of early stage lung cancers.

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Development of a RNA-Seq Based Prognostic Signature in Lung Adenocarcinoma

Abstract: Here, we present the first RNA-seq prognostic signature for lung adenocarcinoma that can provide a powerful prognostic tool for precision oncology as part of an integrated RNA-seq clinical sequencing program.

Cited by 170 publications

References 45 publications

Integrative Analysis of DNA Methylation and Gene Expression Identify a Three-Gene Signature for Predicting Prognosis in Lower-Grade Gliomas

Integrative Analysis of DNA Methylation and Gene Expression Identify a Three-Gene Signature for Predicting Prognosis in Lower-Grade Gliomas

CD109: a multifunctional GPI‐anchored protein with key roles in tumor progression and physiological homeostasis

Prognostic and predictive biomarkers post curative intent therapy

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