Survival analysis across the entire transcriptome identifies biomarkers with the highest prognostic power in breast cancer

Győrffy, Balázs

doi:10.1016/j.csbj.2021.07.014

Cited by 1,252 publications

(1,745 citation statements)

References 38 publications

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“…In SurvExpress, 15 the gene symbols of 23 genes pointed out from the LASSO analysis were input for the analysis, the risk score was calculated automatically, and the deficiency of no more than five genes was allowed. Another online website, Kaplan–Meier Plotter, 16 was also used. A total of 1144 lung cancer patients, including both LUAD and LUSC patients, and the clinical information on sex, smoking status and tumour stage were also recorded.…”

Section: Methodsmentioning

confidence: 99%

A Novel Tool for the Risk Assessment and Personalized Chemo-/Immunotherapy Response Prediction of Adenocarcinoma and Squamous Cell Carcinoma Lung Cancer

Chen¹,

Xu²,

Ge³

et al. 2021

IJGM

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Background The prevalence and cancer-specific death rate of lung cancer (LC) have risen in recent decades. A universally applicable prognostic signature for both adenocarcinoma LC (LUAD) and squamous cell carcinoma LC (LUSC) is still lacking. Methods A total of 453 patients from The Cancer Genome Atlas (TCGA)-LUAD cohort and 452 patients from TCGA-LUSC cohort were enrolled, and a prognostic model was constructed using least absolute shrinkage and selection operator (LASSO) regression analysis based on the consensus prognostic genes in both cohorts. The newly defined pan-lung cancer risk count (PLCRC) of each patient was calculated via the summation formula. Results A total of 23 genes were selected for the calculation of the PLCRC. The PLCRC showed a moderate prognostic value in the entire (p < 0.001, HR: 2.75, AUC: 0.643), LUAD (p < 0.001, HR: 2.51, AUC: 0.636) and LUSC (p < 0.001, HR: 2.89, AUC: 0.656) cohorts. The PLCRC was an independent prognostic factor after adjusting the clinical features. The PLCRC was also effective in nine external validation cohorts and in patients with different clinical features. Activation of extracellular matrix pathways and infiltration of immunocytes promoted the tumorigenesis and development of both LUAD and LUSC. We generated a universally applicable prognostic signature, the PLCRC, which could dichotomize patients with significantly different clinical outcomes and guide the clinical treatment of LC patients. Chemotherapy is more suitable for patients with a low PLCRC, while anti-cytotoxic T-lymphocyte-associated protein 4 immunotherapy is more suitable for patients with a high PLCRC. Conclusion We established and validated a newly defined prognostic signature, the PLCRC, for both LUAD and LUSC patients and provided clinical strategies for patients from different risk subgroups.

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Section: Methodsmentioning

confidence: 99%

A Novel Tool for the Risk Assessment and Personalized Chemo-/Immunotherapy Response Prediction of Adenocarcinoma and Squamous Cell Carcinoma Lung Cancer

Chen¹,

Xu²,

Ge³

et al. 2021

IJGM

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“…The prognostic value for relapse-free survival (RFS) of survival-related DEGs was tested with the Kaplan–Meier Plotter tool, which includes mRNA gene chip data of 7830 breast cancer patients across 55 independent databases [ 23 ]. The analyses were performed following the instructions, and the inclusion criteria for patients selection were: ER+ (IHC)/HER2− (array), had at least 10 years follow-up, received adjuvant systemic treatment (the menopausal status was unavailable).…”

Section: Methodsmentioning

confidence: 99%

Molecular Prognostic Factors for Distant Metastases in Premenopausal Patients with HR+/HER2− Early Breast Cancer

Ni¹,

Kumbrink

Mayr

et al. 2021

JPM

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Molecular factors that drive metastasis in premenopausal patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2−), early breast cancer (EBC) are largely unknown. To identify markers/signatures contributing to metastasis, we analyzed molecular changes in tumors from premenopausal patients who developed metastasis (M1) and who did not (M0). Ninety-seven premenopausal patients with HR+/HER2− EBC were included (M1, n = 48, median distant metastasis-free survival (DMFS): 54 (7–184) months; M0, n = 49, median follow-up: 149 (121–191) months). Gene expression profiling on tumor RNA (Breast Cancer 360TM panel, Nanostring) was performed, followed by comprehensive bioinformatic and statistical analyses. Significantly enhanced ROR (risk of recurrence) scores and reduced signature scores of PGR (progesterone receptor), claudin-low, and mammary stemness were determined in M1. These differences were significantly associated with shorter DMFS in univariate survival analyses. Gene set enrichment analysis showed an enriched mTORC1 pathway in M1. Moreover, a metastasis signature of 19 differentially expressed genes (DEGs) that were DMFS-related was defined. Multivariate analysis including the four signatures, 19 DEGs, pN, and pT status, identified LRP2, IBSP, and SCUBE2 as independent prognostic factors. We identified prognostic gene signatures and single-gene markers for distant metastasis in premenopausal HR+/HER2− EBC potentially applicable in future clinical practice.

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“…Additonally, the full spectrum of tumors that collapse upon loss of RNF4 is still unknown. For example, high levels of RNF4 correlate with longer survival times in lung cancer but are associated with poor prognosis in gastric cancer [ 132 ].…”

Section: Rnf4 Is Associated With Resistance To Therapy and Poor Prognosis In Human Cancermentioning

confidence: 99%

From the Evasion of Degradation to Ubiquitin-Dependent Protein Stabilization

Ahmad

Oknin-Vaisman

Bitman-Lotan

et al. 2021

Cells

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A hallmark of cancer is dysregulated protein turnover (proteostasis), which involves pathologic ubiquitin-dependent degradation of tumor suppressor proteins, as well as increased oncoprotein stabilization. The latter is due, in part, to mutation within sequences, termed degrons, which are required for oncoprotein recognition by the substrate-recognition enzyme, E3 ubiquitin ligase. Stabilization may also result from the inactivation of the enzymatic machinery that mediates the degradation of oncoproteins. Importantly, inactivation in cancer of E3 enzymes that regulates the physiological degradation of oncoproteins, results in tumor cells that accumulate multiple active oncoproteins with prolonged half-lives, leading to the development of “degradation-resistant” cancer cells. In addition, specific sequences may enable ubiquitinated proteins to evade degradation at the 26S proteasome. While the ubiquitin-proteasome pathway was originally discovered as central for protein degradation, in cancer cells a ubiquitin-dependent protein stabilization pathway actively translates transient mitogenic signals into long-lasting protein stabilization and enhances the activity of key oncoproteins. A central enzyme in this pathway is the ubiquitin ligase RNF4. An intimate link connects protein stabilization with tumorigenesis in experimental models as well as in the clinic, suggesting that pharmacological inhibition of protein stabilization has potential for personalized medicine in cancer. In this review, we highlight old observations and recent advances in our knowledge regarding protein stabilization.

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Survival analysis across the entire transcriptome identifies biomarkers with the highest prognostic power in breast cancer

Abstract: Graphical abstract

Cited by 1,252 publications

References 38 publications

A Novel Tool for the Risk Assessment and Personalized Chemo-/Immunotherapy Response Prediction of Adenocarcinoma and Squamous Cell Carcinoma Lung Cancer

A Novel Tool for the Risk Assessment and Personalized Chemo-/Immunotherapy Response Prediction of Adenocarcinoma and Squamous Cell Carcinoma Lung Cancer

Molecular Prognostic Factors for Distant Metastases in Premenopausal Patients with HR+/HER2− Early Breast Cancer

From the Evasion of Degradation to Ubiquitin-Dependent Protein Stabilization

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