scholarly journals The Target E2F Family Gene PTTG1 for Prediction of Distant Relapse-Free Survival in Breast Cancer Patients Receiving Taxane and Anthracycline-Based NACT

2021 ◽  
Author(s):  
Yu-hao Xu ◽  
Yao-qiang Du ◽  
Qing-hui Zheng ◽  
Qiu-ran Xu ◽  
Xuli Meng
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Target Genes ◽  
Cox Regression ◽  
Gene Expression Omnibus ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Distant Relapse ◽  
Potential Biomarker

Abstract Background: The breast cancer is the most commonly diagnosed cancer in recent years. The use of neoadjuvant chemotherapy (NACT) makes a significant contribution to chemotherapy in breast cancer. We aimed to develop the novel model as a predictor of distant relapse-free survival (DRFS) in breast cancer patients receiving taxane and anthracycline-based NACT.Methods: We collected the mRNA expression datasets of patients from GSE25055 and GSE25065 in Gene Expression Omnibus (GEO). Univariate and Multivariate Cox Regression Analyses were conducted to achieve the prognostic genes that associated with DRFS. Moreover, the E2F target genes were obtained from GSEA. We obtained the intersection genes between the prognostic genes and E2F target genes, then validated in GSE32603 dataset. And we established a nomogram model based on PTTG1 expression level and several clinical characteristics.Results: There were 95 genes confirmed to be associated with DRFS both in GSE25055 and GSE25065. And PTTG1 was validated as a gene related to DRFS and associated with E2F target hallmark using GSEA analysis and chosen as our target gene. The AUC of PTTG1 model was 0.682 indicating a relatively poor prediction performance. Then a novel nomogram was conducted, the receiver operating characteristic (AUC=0.849), C-index (0.805) and calibration plots were applied to assess the effect of this model.Conclusion: Our study found that the E2F target genes, such as the PTTG1 may serve as a potential biomarker in breast cancer, and provided superior estimation of DRFS, which can guide the clinical practice in NACT of breast cancer.

scholarly journals The target E2F family gene PTTG1 for prediction of distant relapse-free survival in breast cancer patients receiving taxane and anthracycline-based NACT

2021 ◽  
Author(s):  
Yuhao Xu ◽  
Yaoqiang Du ◽  
Qinghui Zheng ◽  
Hongchao Tang ◽  
Yangyang Qian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Target Genes ◽  
Cox Regression ◽  
Gene Expression Omnibus ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Distant Relapse ◽  
Potential Biomarker

Abstract Background Recent years, the breast cancer became the most commonly diagnosed cancer. The use of neoadjuvant chemotherapy (NACT) makes a significant contribution to chemotherapy in breast cancer. We aimed to develop the novel model as a predictor of distant relapse-free survival (DRFS) in breast cancer patients receiving taxane and anthracycline-based NACT. Methods We collected the mRNA expression datasets of patients from GSE25055 and GSE25065 in Gene Expression Omnibus (GEO). Univariate and Multivariate Cox Regression Analyses were conducted to achieve the prognostic genes that associated with DRFS. Moreover, the E2F targets genes were obtained from GSEA. We obtained the intersection genes between the prognostic genes and E2F target genes, then validated in GSE32603 dataset. And we established a nomogram model based on PTTG1 expression level and several clinical characteristics. Results A novel nomogram was conducted. The receiver operating characteristic (AUC = 0.849), C-index (0.805) and calibration plots were applied to assess the effect of this model. Conclusion Our study found that the E2F target genes, such as the PTTG1 may serve as a potential biomarker in breast cancer, and provided superior estimation of DRFS, which can guide the clinical practice in NACT of breast cancer.

Involvement of NK cell molecular signatures in favorable prognosis of breast cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10565-10565
Author(s):  
Maria Libera Ascierto ◽  
Michael O Idowu ◽  
Yingdong Zhao ◽  
Davide Bedognetti ◽  
Paolo Antonio Ascierto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Nk Cells ◽  
Cancer Patients ◽  
Adhesion Molecules ◽  
Nk Cell ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Favorable Prognosis ◽  
Activating Receptors

10565 Background: Tumor cell recognition by NK cells is mediated by the interaction of activating and inhibitory NK cell receptors with their ligands expressed on tumor cells. In addition, NK cells express adhesion molecules that facilitate formation of the immunological synapse with the tumor targets. Here, we investigated whether the coordinate expression of NK activating receptors and adhesion molecules could provide a signature to segregate breast cancer patients into relapse and relapse-free outcomes. Methods: Gene expression profiling, RT-PCR screening and survival analysis were performed on RNA extracted from primary breast cancers. Tumors were obtained from patients experiencing either 5-8 years relapse-free survival or tumor relapse within 1-3 years following initial treatment. Results: Tumors from patients with a favorable prognosis were characterized by increased expression of genes involved in NK cell interaction with tumor cells and its activation signaling. In particular, up-regulation of Natural Cytotoxicity Receptors (NCRs), leukocyte function-associated antigen 1 (LFA-1), CD226 (DNAM-1) and CD96 was observed in relapse-free patients. Thus, the expression of the NK activating receptors and relevant adhesion molecules involved in NK cell:target interactions can predict relapse free survival in breast cancer patients. Conclusions: Results from the present study, highlighted the effector cooperation between the innate and adaptive immune components within the tumor microenvironment. The NK cells parameters identified in this study, together with the prognostic B and T cell signatures previously reported by us, represent a powerful tool for predicting breast cancer outcome which might be easily introduced in clinical practice.

scholarly journals High mutation burden of circulating cell‐free DNA in early‐stage breast cancer patients is associated with a poor relapse‐free survival

2020 ◽  
Vol 9 (16) ◽  
pp. 5922-5931
Author(s):  
Jouni Kujala ◽  
Jaana M. Hartikainen ◽  
Maria Tengström ◽  
Reijo Sironen ◽  
Veli‐Matti Kosma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Early Stage Breast Cancer ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Cell Free Dna ◽  
Free Survival ◽  
Free Dna ◽  
Mutation Burden

scholarly journals Prognostic impact of the glypican family of heparan sulfate proteoglycans on the survival of breast cancer patients

2021 ◽  
Author(s):  
Paulina Karin Grillo ◽  
Balázs Győrffy ◽  
Martin Götte
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Heparan Sulfate ◽  
Cancer Patients ◽  
Heparan Sulfate Proteoglycans ◽  
Prognostic Impact ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Free Survival ◽  
The Impact

Abstract Purpose Dysregulated expression of proteoglycans influences the outcome and progression of numerous cancers. Several studies have investigated the role of individual glypicans in cancer, however, the impact of the whole glypican family of heparan sulfate proteoglycans on prognosis of a large patient cohort of breast cancer patients has not yet been investigated. In the present study, our aim was to investigate the prognostic power of the glypicans in breast cancer patients. Methods We used a public database including both gene expression data and survival information for 3951 breast cancer patients to determine the prognostic value of glypicans on relapse-free survival using Cox regression analysis. Moreover, we performed quantitative Real-Time PCR to determine glypican gene expression levels in seven representative breast cancer cell lines. Results We found that high GPC3 levels were associated with a better prognosis in overall breast cancer patients. When stratified by hormone receptor status, we found that in worse prognosis subtypes low GPC1 levels correlate with a longer relapse-free survival, and in more favorable subtypes low GPC6 was associated with longer survival. Conclusion Our study concludes that glypicans could act as subtype-specific biomarkers for the prognosis of breast cancer patients and sparks hope for future research on glypicans possibly eventually providing targets for the treatment of the disease.

Validation of an RT-PCR multi-gene prognostic signature for distant metastasis in node negative (N-), ER positive (ER+) breast cancer patients using FFPE sections

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21009-21009
Author(s):  
A. Tutt ◽  
A. Wang ◽  
R. Springall ◽  
K. Lau ◽  
K. Ryder ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Distant Metastasis ◽  
Tumor Size ◽  
Cox Regression ◽  
Risk Groups ◽  
Breast Cancer Patients ◽  
Prognostic Signature ◽  
Rt Pcr ◽  
Free Survival

21009 Background: We sought to validate a previously developed 14-gene prognostic signature and a metastasis score (MS) that predicted distant metastasis in N-, ER+ breast cancer patients in an independent sample set of patients without systemic treatment. The genes consisted primarily of proliferation genes involved in p53 and TNF signaling pathways. Methods: : A cohort of 294 N-, ER+ breast cancer patients from Guy's Hospitals, London, UK without systemic therapy were tested. The cohort had a mean age of 55.5 yrs with 49% > 55 yrs, mean tumor size of 1.93 (max. 3) cm, and a median follow up of 14.3 yrs. The primary endpoint was distant metastasis free survival. RT-PCR was carried out on fixed sections. The MS was calculated. Results: The mean MS (SD) was 0.44 (0.59) with a range of -1.31 to 2.0. Hazard of distant metastasis increased 3.02 fold (95% CI 1.91–4.76, p <0.0001) per unit increase in MS from Cox model. The pre-determined cut point of zero was used to stratify patients into low- and high-risk groups. The 5-yr distant-metastasis-free survival rate (DMFSR) for low- and high-risk groups were 1 and 0.86 (SE 0.024); the 10-yr DMFSR were 0.97 (0.021) and 0.77 (0.030), respectively. Univariate Cox regression analyses indicated that MS (hazard ratio (HR) 5.65, 95% CI 2.05–15.56, p=0.008), tumor size (HR 1.62, p=0.0047) and tumor grade (HR 2.52, p=0.036) were significant but age was not. Multivariate Cox regression indicated that the signature had independent prognostic value with a HR of 4.71 (1.42–15.61, p=0.011) after adjusting for age, tumor size and grade. AUC of MS at 5-and 10-yr were 0.78 (0.71–0.85, p<0.001) and 0.73 (0.66–0.80, p<0.001) with sensitivities of 1 and 0.96 and specificities of 0.31 and 0.31 at zero cut point, respectively. The differential risk between the median MS scores of the lowest and highest deciles was 8-fold. Conclusions: A previously defined RT-PCR prognostic signature for N-, ER+ patients has been confirmed. A metastasis score that quantifies distant metastasis risk, not confounded with treatment effect can complement treatment response predictors. Insight on natural history of tumors is critical for evaluating impact of therapy. No significant financial relationships to disclose.

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