Online Survival Analysis Software to Assess the Prognostic Value of Biomarkers Using Transcriptomic Data in Non-Small-Cell Lung Cancer

Győrffy, Balázs; Surowiak, Paweł; Budczies, Jan; Lánczky, András

doi:10.1371/journal.pone.0082241

Cited by 1,579 publications

(1,636 citation statements)

References 43 publications

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“…To investigate the role of PHB in the breast cancer cell growth, plasmids encoding PHB were transfected into ER-positive breast cancer cell lines MCF-7 and T47D, and cells were collected at different time points (24,48, or 72 h) to determine cell survival rates. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

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Prohibitin promotes androgen receptor activation in ER-positive breast cancer

Liu

Zhang

et al. 2017

Cell Cycle

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Prohibitin (PHB) is an evolutionarily conserved protein with multiple functions in both normal and cancer cells. Androgen receptor (AR) was reported to act as a different role in the ER-positive and ER-negative breast cancer. However, little is known about the role of PHB and whether PHB could regulate AR expression in the ER-positive breast cancer. Here, we determined the expression and clinical outcomes of PHB in breast cancer samples using 121 breast cancer tissues and published databases, and investigated the role of PHB in breast cancer cell growth, apoptosis and cell cycle arrest in the ER-positive breast cancer cells. We obtained the expression of PHB is significantly low in breast cancer samples, and low PHB expression positively correlated with poor prognosis of breast cancer. We detected that PHB could inhibit breast cancer cell proliferation, change cell cycle distribution and promote cell apoptosis in the ER-positive breast cancer cells. Moreover, we found PHB could significantly increase AR expression in both mRNA and protein levels in the ER-positive breast cancer cells. Additionally, a significant positive correlation between PHB and AR expression was identified in the 121 breast cancer tissues. PHB and AR expression are associated with prognosis in the ER-positive breast cancer patients. Our results indicate that PHB promotes AR activation in ER-positive breast cancer, making PHB and AR potential molecular targets for ER-positive breast cancer therapy.

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Section: Resultsmentioning

confidence: 99%

“…Kaplan-Meier survival analyses for disease outcomes were performed using the online database (www.kmplot.com) and the percentiles of the patients between the upper and lower quartiles were auto-selected based on the computed best performing thresholds as cutoffs. 24 …”

Section: Clinical Samples and Survival Analysismentioning

confidence: 99%

Prohibitin promotes androgen receptor activation in ER-positive breast cancer

Liu

Zhang

et al. 2017

Cell Cycle

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“…Interestingly, TP53 was also found highly expressed in TLR7 hi patients (Figure 7D). We then searched for correlation between the level of gene expression and survival of adenocarcinoma lung cancer patients, using the public software KM plotter 13 . High expression of KRT-7 and KRT-19, as well as that of NME1 and TP53, significantly correlated with poor clinical outcome (Figure 7E).…”

Section: Resultsmentioning

confidence: 99%

Toll like receptor 7 expressed by malignant cells promotes tumor progression and metastasis through the recruitment of myeloid derived suppressor cells

et al. 2018

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In non-small cell lung carcinoma (NSCLC), stimulation of toll-like receptor 7 (TLR7), a receptor for single stranded RNA, is linked to tumor progression and resistance to anticancer chemotherapy. However, the mechanism of this effect has been elusive. Here, using a murine model of lung adenocarcinoma, we demonstrate a key role for TLR7 expressed by malignant (rather than by stromal and immune) cells, in the recruitment of myeloid derived suppressor cells (MDSCs), induced after TLR7 stimulation, resulting in accelerated tumor growth and metastasis. In adenocarcinoma patients, high TLR7 expression on malignant cells was associated with poor clinical outcome, as well as with a gene expression signature linked to aggressiveness and metastastic dissemination with high abundance of mRNA encoding intercellular adhesion molecule 1 (ICAM-1), cytokeratins 7 and 19 (KRT-7 and 19), syndecan 4 (SDC4), and p53. In addition, lung tumors expressing high levels of TLR7 have a phenotype of epithelial mesenchymal transition with high expression of vimentin and low abundance of E-cadherin. These data reveal a crucial role for cancer cell-intrinsic TLR7 expression in lung adenocarcinoma progression.

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“…We used a previously established lung cancer microarray database33 that contains 2,437 samples measured using Affymetrix HGU133 microarrays (1,800 samples from GEO, http://www.ncbi.nlm.nih.gov/geo/), 504 samples from CaArray project, http://cabig.cancer.gov/ and 133 samples from the TCGA repository). Gene chips were normalized with the MAS5 algorithm by the Affy Bioconductor library.…”

Section: Methodsmentioning

confidence: 99%

KRAS driven expression signature has prognostic power superior to mutation status in non‐small cell lung cancer

Nagy

Pongor

Szabó

et al. 2016

Intl Journal of Cancer

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KRAS is the most frequently mutated oncogene in non‐small cell lung cancer (NSCLC). However, the prognostic role of KRAS mutation status in NSCLC still remains controversial. We hypothesize that the expression changes of genes affected by KRAS mutation status will have the most prominent effect and could be used as a prognostic signature in lung cancer.We divided NSCLC patients with mutation and RNA‐seq data into KRAS mutated and wild type groups. Mann‐Whitney test was used to identify genes showing altered expression between these cohorts. Mean expression of the top five genes was designated as a “transcriptomic fingerprint” of the mutation. We evaluated the effect of this signature on clinical outcome in 2,437 NSCLC patients using univariate and multivariate Cox regression analysis.Mutation of KRAS was most common in adenocarcinoma. Mutation status and KRAS expression were not correlated to prognosis. The transcriptomic fingerprint of KRAS include FOXRED2, KRAS, TOP1, PEX3 and ABL2. The KRAS signature had a high prognostic power. Similar results were achieved when using the second and third set of strongest genes. Moreover, all cutoff values delivered significant prognostic power (p < 0.01). The KRAS signature also remained significant (p < 0.01) in a multivariate analysis including age, gender, smoking history and tumor stage.We generated a “surrogate signature” of KRAS mutation status in NSCLC patients by computationally linking genotype and gene expression. We show that secondary effects of a mutation can have a higher prognostic relevance than the primary genetic alteration itself.

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Online Survival Analysis Software to Assess the Prognostic Value of Biomarkers Using Transcriptomic Data in Non-Small-Cell Lung Cancer

Cited by 1,579 publications

References 43 publications

Prohibitin promotes androgen receptor activation in ER-positive breast cancer

Prohibitin promotes androgen receptor activation in ER-positive breast cancer

Toll like receptor 7 expressed by malignant cells promotes tumor progression and metastasis through the recruitment of myeloid derived suppressor cells

KRAS driven expression signature has prognostic power superior to mutation status in non‐small cell lung cancer

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