Prognostic value of PD-L1 gene expression with Recurrence Score and 70-gene signature in patients with ER+/HER2- early breast cancer.

550 Background: We have previously demonstrated that PD-L1 mRNA expression can serve as prognostic biomarker in breast cancer (BC). In ER+/HER2- BC, RS and 70-gene signature are used to predict the risk of recurrence and benefit from chemotherapy. Methods: Discovery cohort (cohort 1) included 302 patients diagnosed with primary ER+/HER2- BC (1997-2005) in Stockholm health care region. Gene expression profiling has been performed using DNA microarrays (GSE48091) while information regarding tumor characteristics, treatment and follow-up have been obtained. TCGA’s dataset including 590 ER+/HER2- patients, was used as validation cohort (cohort 2). Kaplan–Meier estimates and Cox regression univariate/multivariable analyses were performed using breast cancer-specific survival(BCSS) and progression-free interval (PFI) as endpoints in cohorts 1 and 2, respectively. Gene signature scores were calculated using the R genefu package. Likelihood ratio (LR) tests and concordance indices (c-indices) were used to assess each score’s added prognostic value. Results: PD-L1 mRNA expression (treated as a continuous variable) was independently associated with better BCSS in cohort 1 (HR = 0.72; 95% CI = 0.58-0.90;p = 0.003) and with better PFI in cohort 2 (HR = 0.67; 95% CI = 0.50-0.90; p = 0.008) in the multivariable analysis. PD-L1 provided significant additional prognostic information beyond that of both RS alone (LR-Δχ2= 9.6; p = 0.002 and LR-Δχ2= 9.7; p = 0.002, in cohorts 1 and 2, respectively), and 70-gene signature score alone (LR-Δχ2= 10.4; p = 0.001 and LR-Δχ2= 9.2; p = 0.002 in cohort 1 and 2, respectively). C-indices for PD-L1 + RS vs RS were 0.65 vs 0.60 (cohort 1) and 0.66 vs 0.60 (cohort 2), and for PD-L1 + 70-gene vs 70-gene were 0.65 vs 0.59 (cohort 1) and 0.64 vs 0.54 (cohort 2), respectively. Conclusions: PD-L1 gene expression was correlated with better outcomes and can provide added prognostic value to RS and 70-gene signature scores in ER+/HER2- BC.

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Ovarian cycle stage critically affects 21-gene recurrence scores in Mmtv-Pymt mouse mammary tumours

BMC Cancer ◽

10.1186/s12885-021-08496-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sarah M. Bernhardt ◽

Pallave Dasari ◽

Danielle J. Glynn ◽

Lucy Woolford ◽

Lachlan M. Moldenhauer ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Menstrual Cycle ◽

Recurrence Score ◽

Gene Signature ◽

Ovarian Cycle ◽

Oncotype Dx ◽

Mammary Tumours ◽

Er Positive ◽

The Impact

Abstract Background The Oncotype DX 21-gene Recurrence Score is predictive of adjuvant chemotherapy benefit for women with early-stage, estrogen receptor (ER)-positive, HER2-negative breast cancer. In premenopausal women, fluctuations in estrogen and progesterone during the menstrual cycle impact gene expression in hormone-responsive cancers. However, the extent to which menstrual cycling affects the Oncotype DX 21-gene signature remains unclear. Here, we investigate the impact of ovarian cycle stage on the 21-gene signature using a naturally cycling mouse model of breast cancer. Methods ER-positive mammary tumours were dissected from naturally cycling Mmtv-Pymt mice at either the estrus or diestrus phase of the ovarian cycle. The Oncotype DX 21-gene signature was assessed through quantitative real time-PCR, and a 21-gene experimental recurrence score analogous to the Oncotype DX Recurrence Score was calculated. Results Tumours collected at diestrus exhibited significant differences in expression of 6 Oncotype DX signature genes (Ki67, Ccnb1, Esr1, Erbb2, Grb7, Bag1; p ≤ 0.05) and a significant increase in 21-gene recurrence score (21.8 ± 2.4; mean ± SEM) compared to tumours dissected at estrus (15.5 ± 1.9; p = 0.03). Clustering analysis revealed a subgroup of tumours collected at diestrus characterised by increased expression of proliferation- (p < 0.001) and invasion-group (p = 0.01) genes, and increased 21-gene recurrence score (p = 0.01). No correlation between ER, PR, HER2, and KI67 protein abundance measured by Western blot and abundance of mRNA for the corresponding gene was observed, suggesting that gene expression is more susceptible to hormone-induced fluctuation compared to protein expression. Conclusions Ovarian cycle stage at the time of tissue collection critically affects the 21-gene signature in Mmtv-Pymt murine mammary tumours. Further studies are required to determine whether Oncotype DX Recurrence Scores in women are similarly affected by menstrual cycle stage.

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Outcome of patients with an ultralow risk 70-gene signature in the MINDACT trial.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.500 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 500-500

Author(s):

Josephine Lopes Cardozo ◽

Caroline Drukker ◽

Marjanka Schmidt ◽

Laura van 't Veer ◽

Annuska Glas ◽

...

Keyword(s):

Breast Cancer ◽

Cox Regression ◽

Gene Signature ◽

Distant Recurrence ◽

Low Risk ◽

Risk Category ◽

Breast Cancer Specific Survival ◽

Cancer Specific Survival ◽

Clinical Risk ◽

Risk Patients

500 Background: Gene signatures have proven successful in identifying patients with a low risk of distant recurrence who could forego chemotherapy (CT) and are currently included in international treatment guidelines for breast cancer. For the 70-gene signature (MammaPrint) an additional threshold was established within the low risk category to identify patients with an ultralow risk of distant recurrence. In independent cohorts, these patients had excellent breast cancer specific survival at 15 years, suggesting that ultralow risk cancers represent indolent disease (Esserman, JAMA Oncol 2017, Delahaye, BC Res Treat 2017). Here we evaluate survival of patients with an ultralow risk 70-gene signature who participated in the randomized phase 3 MINDACT trial (Piccart, Lancet Oncol 2021). Methods: Of the 6,693 patients enrolled in the MINDACT trial (EORTC 10041/BIG 3-04) between 2007-2011, profiling revealed an ultralow risk 70-gene signature in 1,000 patients (15%). We assessed 5- and 8-year distant metastasis free interval (DMFI) and breast cancer specific survival (BCSS) in patients stratified by 70-gene signature result (high, low, ultralow), and within the ultralow risk group stratified by clinical risk. For these exploratory analyses, we used Kaplan-Meier estimates for time to event endpoints and Cox-regression models to calculate hazard ratio’s (HR). Results: Median follow-up was 8.7 years. Among the ultralow risk patients (n = 1,000), 67% were ≥50 years, 81% had tumors < 2cm, 80% were lymph node negative, 96% had grade 1 or 2 tumors and 99% were ER-positive. Systemic therapy was received by 83% of patients (69% endocrine therapy (ET), 14% ET + CT) and 16% received no adjuvant systemic treatment (AST). Survival estimates for all endpoints are shown in the table; 8-year DMFI was 97.0% (95% CI 95.8-98.1) for ultralow risk. The 8-year DMFI in ultralow risk patients who received no AST or ET only was 97.8% (95% CI 95.3-100) and 97.4% (95% CI 96.1-98.7), respectively. The HR for DMFI was 0.66 (95% CI 0.46-0.95) for ultralow vs low risk, after adjusting for tumor and treatment characteristics (preliminary results). Conclusions: In this prospective study, patients with an ultralow risk 70-gene signature have an excellent prognosis with 8-year BCSS above 99% regardless of clinical risk status, and with an 8-year DMFI of 95-98%.[Table: see text]

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Comprehensive Association Analysis of 21-Gene Recurrence Score and Obesity in Chinese Breast Cancer Patients

Frontiers in Oncology ◽

10.3389/fonc.2021.619840 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yiwei Tong ◽

Weiqi Gao ◽

Jiayi Wu ◽

Siji Zhu ◽

Ou Huang ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cancer Patients ◽

Prognostic Value ◽

Single Gene ◽

Menopausal Status ◽

Recurrence Score ◽

Risk Category ◽

Obese Patients ◽

Breast Cancer Patients

PurposeA center-specific 21-gene recurrence score (RS) assay has been validated in Luminal-like, HER2-, pN0-1 Chinese breast cancer patients with both predictive and prognostic value. The association between RS and host factors such as obesity remains unclear. The objectives of the current study are to comprehensively analyze the distribution, single gene expression, and prognostic value of RS among non-overweight, overweight and obese patients.Patients and methodsLuminal-like patients between January 2009 and December 2018 were retrospectively reviewed. Association and subgroup analysis between BMI and RS were conducted. Single-gene expression in RS panel was compared according to BMI status. Disease-free survival (DFS) and overall survival (OS) were calculated according to risk category and BMI status.ResultsAmong 1876 patients included, 124 (6.6%), 896 (47.8%) and 856 (45.6%) had RS < 11, RS 11-25, and RS ≥ 26, respectively. Risk category was significantly differently distributed by BMI status (P=0.033). Obese patients were more likely to have RS < 11 (OR 2.45, 95% CI 1.38-4.35, P=0.002) compared with non-overweight patients. The effect of BMI on RS significantly varied according to menstruation (P<0.05). Compared to non-overweight patients, obese ones presented significantly higher ER, PR, CEGP1, Ki67, CCNB1 and GSTM1 (all P<0.05) mRNA expression, and such difference was mainly observed in postmenopausal population. After a median follow-up of 39.40 months (range 1.67-119.53), RS could significantly predict DFS in whole population (P=0.001). RS was associated with DFS in non-overweight (P=0.046), but not in overweight (P=0.558) or obese (P=0.114) population.ConclusionsRS was differently distributed among different BMI status, which interacted with menopausal status. Estrogen receptor and proliferation group genes were more expressed in obese patients, especially in postmenopausal population.

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Development of a novel lipid metabolism-based risk score model in hepatocellular carcinoma patients

BMC Gastroenterology ◽

10.1186/s12876-021-01638-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Wenjie Wang ◽

Chen Zhang ◽

Qihong Yu ◽

Xichuan Zheng ◽

Chuanzheng Yin ◽

...

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Lipid Metabolism ◽

Liver Cancer ◽

Risk Score ◽

Prognostic Value ◽

Cox Regression ◽

Gene Signature ◽

Related Gene ◽

Patient Prognosis

Abstract Background Liver cancer is one of the most common malignancies worldwide. HCC (hepatocellular carcinoma) is the predominant pathological type of liver cancer, accounting for approximately 75–85 % of all liver cancers. Lipid metabolic reprogramming has emerged as an important feature of HCC. However, the influence of lipid metabolism-related gene expression in HCC patient prognosis remains unknown. In this study, we performed a comprehensive analysis of HCC gene expression data from TCGA (The Cancer Genome Atlas) to acquire further insight into the role of lipid metabolism-related genes in HCC patient prognosis. Methods We analyzed the mRNA expression profiles of 424 HCC patients from the TCGA database. GSEA(Gene Set Enrichment Analysis) was performed to identify lipid metabolism-related gene sets associated with HCC. We performed univariate Cox regression and LASSO(least absolute shrinkage and selection operator) regression analyses to identify genes with prognostic value and develop a prognostic model, which was tested in a validation cohort. We performed Kaplan-Meier survival and ROC (receiver operating characteristic) analyses to evaluate the performance of the model. Results We identified three lipid metabolism-related genes (ME1, MED10, MED22) with prognostic value in HCC and used them to calculate a risk score for each HCC patient. High-risk HCC patients exhibited a significantly lower survival rate than low-risk patients. Multivariate Cox regression analysis revealed that the 3-gene signature was an independent prognostic factor in HCC. Furthermore, the signature provided a highly accurate prediction of HCC patient prognosis. Conclusions We identified three lipid-metabolism-related genes that are upregulated in HCC tissues and established a 3-gene signature-based risk model that can accurately predict HCC patient prognosis. Our findings support the strong links between lipid metabolism and HCC and may facilitate the development of new metabolism-targeted treatment approaches for HCC.

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A Novel Gene Prognostic Signature Based on Differential DNA Methylation in Breast Cancer

Frontiers in Genetics ◽

10.3389/fgene.2021.742578 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chunmei Zhu ◽

Shuyuan Zhang ◽

Di Liu ◽

Qingqing Wang ◽

Ningning Yang ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Dna Methylation ◽

High Risk ◽

Cox Regression ◽

Methylation Status ◽

Gene Signature ◽

Prognostic Signature ◽

Cox Regression Analysis ◽

The Impact

Background: DNA methylation played essential roles in regulating gene expression. The impact of DNA methylation status on the occurrence and development of cancers has been well demonstrated. However, little is known about its prognostic role in breast cancer (BC).Materials: The Illumina Human Methylation450 array (450k array) data of BC was downloaded from the UCSC xena database. Transcriptomic data of BC was downloaded from the Cancer Genome Atlas (TCGA) database. Firstly, we used univariate and multivariate Cox regression analysis to screen out independent prognostic CpGs, and then we identified methylation-associated prognosis subgroups by consensus clustering. Next, a methylation prognostic model was developed using multivariate Cox analysis and was validated with the Illumina Human Methylation27 array (27k array) dataset of BC. We then screened out differentially expressed genes (DEGs) between methylation high-risk and low-risk groups and constructed a methylation-based gene prognostic signature. Further, we validated the gene signature with three subgroups of the TCGA-BRCA dataset and an external dataset GSE146558 from the Gene Expression Omnibus (GEO) database.Results: We established a methylation prognostic signature and a methylation-based gene prognostic signature, and there was a close positive correlation between them. The gene prognostic signature involved six genes: IRF2, KCNJ11, ZDHHC9, LRP11, PCMT1, and TMEM70. We verified their expression in mRNA and protein levels in BC. Both methylation and methylation-based gene prognostic signatures showed good prognostic stratification ability. The AUC values of 3-years, 5-years overall survival (OS) were 0.737, 0.744 in the methylation signature and 0.725, 0.715 in the gene signature, respectively. In the validation groups, high-risk patients were confirmed to have poorer OS. The AUC values of 3 years were 0.757, 0.735, 0.733 in the three subgroups of TCGA dataset and 0.635 in GSE146558 dataset.Conclusion: This study revealed the DNA methylation landscape and established promising methylation and methylation-based gene prognostic signatures that could serve as potential prognostic biomarkers and therapeutic targets.

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Over-expression of SRD5A3 and its prognostic significance in breast cancer

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02377-1 ◽

2021 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Yong-ping Zhang ◽

Wen-ting Na ◽

Xiao-qiang Dai ◽

Ruo-fei Li ◽

Jian-xiong Wang ◽

...

Keyword(s):

Breast Cancer ◽

Regression Analysis ◽

Mrna Expression ◽

Prognostic Value ◽

Cox Regression ◽

Enrichment Analysis ◽

Genetic Alterations ◽

Functional Enrichment ◽

Cox Regression Analysis ◽

Expression Levels

Abstract Objective The study aimed to compare the Steroid 5 alpha-reductase 3 (SRD5A3) expression levels in breast cancer (BC) and normal tissues, to investigate the prognostic value of SRD5A3 mRNA expression in BC patients and to identify the SRD5A3-related signaling pathways using bioinformatics approaches. Methods We evaluated the expression levels of SRD5A3 and survival data in BC patients using different bioinformatic databases. Further, Cox regression analysis was conducted to predict the independent prognostic factors for BC. Moreover, the association of SRD5A3 with clinicopathological factors was measured through LinkedOmics database. And the potential role of SRD5A3 was determined by Gene Ontology and KEGG pathway enrichment analysis. Finally, protein network of SRD5A3 was constructed and genetic alterations were analyzed. Results Bioinformatic data indicated that both mRNA and protein expression levels of SRD5A3 were higher in BC group than those in the normal group (P < 0.05). Besides, BC patients with higher SRD5A3 mRNA expression levels had a lower overall survival (all P < 0.05). Cox regression analysis further demonstrated the independent prognostic value of SRD5A3 in BC (P = 0.015). SRD5A3 mRNA expression was significantly associated with N stage (P < 0.001), age (P < 0.05), and histologic subtype (P < 0.001) but had no significant relationship with other clinical characteristics (all P > 0.05). Moreover, the functional enrichment analysis revealed that the SRD5A3 was involved in metabolism-related pathways (all P < 0.05). Conclusions SRD5A3 was highly expressed in BC tissues and high SRD5A3 expression was related to poorer prognosis. SRD5A3 serves as an oncogene and might function as a potential biomarker for prognosis and a therapeutic target for BC.

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Developing ZNF Gene Signatures Predicting Radiosensitivity of Patients with Breast Cancer

Journal of Oncology ◽

10.1155/2021/9255494 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

Derui Yan ◽

Mingjing Shen ◽

Zixuan Du ◽

Jianping Cao ◽

Ye Tian ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cancer Patients ◽

Cox Regression ◽

Molecular Taxonomy ◽

Gene Signature ◽

The Cancer Genome Atlas ◽

Breast Cancer Patients ◽

Expression Levels ◽

The Relationship

Adjuvant radiotherapy is one of the main treatment methods for breast cancer, but its clinical benefit depends largely on the characteristics of the patient. This study aimed to explore the relationship between the expression of zinc finger (ZNF) gene family proteins and the radiosensitivity of breast cancer patients. Clinical and gene expression data on a total of 976 breast cancer samples were obtained from The Cancer Genome Atlas (TCGA) database. ZNF gene expression was dichotomized into groups with a higher or lower level than the median level of expression. Univariate and multivariate Cox regression analyses were used to evaluate the relationship between ZNF gene expression levels and radiosensitivity. The Molecular Taxonomy Data of the International Federation of Breast Cancer (METABRIC) database was used for validation. The results revealed that 4 ZNF genes were possible radiosensitivity markers. High expression of ZNF644 and low expression levels of the other 3 genes (ZNF341, ZNF541, and ZNF653) were related to the radiosensitivity of breast cancer. Hierarchical cluster, Cox, and CoxBoost analysis based on these 4 ZNF genes indicated that patients with a favorable 4-gene signature had better overall survival on radiotherapy. Thus, this 4-gene signature may have value for selecting those patients most likely to benefit from radiotherapy. ZNF gene clusters could act as radiosensitivity signatures for breast cancer patients and may be involved in determining the radiosensitivity of cancer.

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Molecular Characterization and Mortality From Breast Cancer in Men

Journal of Clinical Oncology ◽

10.1200/jco.2017.76.8861 ◽

2018 ◽

Vol 36 (14) ◽

pp. 1396-1404 ◽

Cited By ~ 21

Author(s):

Suleiman Alfred Massarweh ◽

George W. Sledge ◽

Dave P. Miller ◽

Debbie McCullough ◽

Valentina I. Petkov ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Overall Survival ◽

Progesterone Receptor ◽

Survival Data ◽

Recurrence Score ◽

Progressive Increase ◽

Cancer Specific Survival ◽

Men And Women ◽

Breast Cancer In Men

Purpose Limited data exist on the molecular biology, treatment, and outcomes of breast cancer in men, and much of our understanding in this area remains largely an extrapolation from data in women with breast cancer. Materials and Methods We studied men and women with hormone receptor–positive breast cancer and the 21-gene Breast Recurrence Score (RS) results. Differences in clinical characteristics and gene expression were determined, and distribution of RS results was correlated with 5-year breast cancer–specific survival (BCSS) and overall survival. Results There were 3,806 men and 571,115 women. Men were older than women (mean age, 64.2 v 59.1 years; P < .001). RS < 18 predominated in both genders, but RS ≥ 31 was more frequent in men (12.4% v 7.4%; P < .001), as were very low scores (RS < 11; 33.8% v 22.1%; P < .001). Mean gene expression was higher in men for the estrogen receptor (ER), proliferation, and invasion groups. ER was lowest and progesterone receptor was highest in women younger than 50 years of age, with a progressive increase in ER with age. Men younger than 50 years of age had slightly lower ER and progesterone receptor compared with older men. Survival data were available from SEER for 322 men and 55,842 women. Five-year BCSS was 99.0% (95% CI, 99.3% to 99.9%) and 95.9% (95% CI, 87.6% to 98.7%) for men with RS < 18 and RS 18-30, respectively, and for women, it was 99.5% (95% CI, 99.4% to 99.6%) and 98.6% (95% CI, 98.4% to 98.8%), respectively. RS ≥ 31 was associated with an 81.0% 5-year BCSS in men (95% CI, 53.3% to 93.2%) and 94.9% 5-year BCSS (95% CI, 93.9% to 95.7%) in women. Five-year BCSS and overall survival were lower in men than in women. Conclusion This study reveals some distinctive biologic features of breast cancer in men and an important prognostic role for RS testing in both men and women.

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The relationship between quantitative HER2 gene expression by the 21-gene RT-PCR assay and adjuvant trastuzumab (H) benefit in NCCTG (Alliance) N9831.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.520 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 520-520 ◽

Cited By ~ 1

Author(s):

Edith A. Perez ◽

Steven M Butler ◽

Amylou C. Dueck ◽

Frederick L. Baehner ◽

Farid Jamshidian ◽

...

Keyword(s):

Gene Expression ◽

Mrna Expression ◽

Cox Regression ◽

Recurrence Score ◽

Her2 Expression ◽

Rt Pcr ◽

Her2 Breast Cancer ◽

Gene Assay ◽

Her2 Mrna ◽

The Relationship

520 Background: There is considerable interest in developing HER2 testing criteria for adjuvant H. We used the 21-gene assay to examine the relationship of HER2 mRNA to benefit from H. Methods: N9831 compared adjuvant chemotherapy AC-T to concurrent chemotherapy-trastuzumab AC-TH in stage I-III HER2+ breast cancer. Recurrence Score (RS) and HER2 mRNA expression were determined by Oncotype DX (neg<10.7, equiv 10.7 to <11.5, and pos ≥11.5 log2 expression units). Cox regression was used to assess the association of HER2 expression with H benefit for distant recurrence. Results: Median follow-up: 7.4 yrs. Of 1,940 total pts, 901 had consent and sufficient tissue. HER2 by RT-PCR was neg in 130 (14%), equiv in 85 (9%), and pos in 686 (76%) pts. Concordance between HER2 assessments was 95% for RT-PCR vs central IHC (>10% + cells = +), 91% for RT-PCR vs central FISH (≥2.0 = pos) and 94% for central IHC vs central FISH. In the primary analysis, the association of HER2 expression with H benefit was marginally non-significant (P=0.057). In hormone receptor pos pts (local IHC) the association was significant (P=0.002). The association was nonlinear with the greatest estimated benefit at lower and higher HER2 mRNA expression levels. The observed treatment benefit in low HER2 pts was not due to imbalance between arms in RS and individual gene expression values. Conclusions: Concordance among HER2 assessments by central IHC, FISH, and RT-PCR was high. Association of HER2 mRNA expression with H benefit was marginally non-significant. A consistent benefit of trastuzumab irrespective of mHER2 levels was observed in the pts with either IHC+ or FISH+ tumors. Benefit was observed in pts with high HER2 by RT-PCR but also observed for the small groups of pts with negative results by quantitative RT-PCR or FISH (Table). Plausible mechanisms for this observation will be discussed. [Table: see text]

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Identification of a 9-Gene Prognostic signature for breast cancer

10.21203/rs.3.rs-26949/v1 ◽

2020 ◽

Author(s):

Zelin Tian ◽

Jianing Tang ◽

Xing Liao ◽

Qian Yang ◽

Yumin Wu ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Overall Survival ◽

Regression Analysis ◽

Cox Regression ◽

Risk Group ◽

Disease Free Survival ◽

Gene Signature ◽

Prognostic Signature ◽

Cox Regression Analysis

Abstract Background Breast cancer (BRCA) is the most common cancer among women worldwide and results in the second leading cause of woman cancer death.Methods This study sought to develop a prognostic gene signature to predict the prognosis of patients with BRCA. Studies were performed using the genome-wide data of BRCA patients from the Gene Expression Omnibus dataset (GSE20685, GSE42568, GSE20711, GSE88770). Univariate COX regression analysis was used to determine the association between gene expression levels and overall survival(OS) in each dataset. Taking P value < 0.05 as the inclusion criterion, the common genes in all datasets were selected as prognostic genes, and a 9-gene prognostic signature was developed.Results The Kaplan-Meier survival curve was constructed using log-rank test to assess survival differences. The overall survival of patients in the low-risk group was significantly higher than that in the high-risk group. ROC analysis showed that this 9-gene signature showed good diagnostic efficiency both in overall survival(OS) and disease free survival(DFS). The 9-gene signature was further validated using GSE16446 dataset. In addition, multiple Cox regression analysis showed that this 9-gene signature was an independent risk factor. Finally, we established a nomogram that integrates conventional clinicopathological features and 9-gene signature. The analysis of the calibration plots showed that the nomogram has good performance.Conclusions This study has developed a reliable 9-gene prognostic signature, which is of great value in predicting the prognosis of BRCA and will help to make personalized treatment decisions for patients at different risk score.

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