Dataset Information

Unbiased Lipidomic Profiling of Triple-Negative Breast Cancer Tissues Reveals the Association of Sphingomyelin Levels with Patient Disease-Free Survival.

ABSTRACT: The reprogramming of lipid metabolism is a hallmark of many cancers that has been shown to promote breast cancer progression. While several lipid signatures associated with breast cancer aggressiveness have been identified, a comprehensive lipidomic analysis specifically targeting the triple-negative subtype of breast cancer (TNBC) may be required to identify novel biomarkers and therapeutic targets for this most aggressive subtype of breast cancer that still lacks effective therapies. In this current study, our global LC-MS-based lipidomics platform was able to measure 684 named lipids across 15 lipid classes in 70 TNBC tumors. Multivariate survival analysis found that higher levels of sphingomyelins were significantly associated with better disease-free survival in TNBC patients. Furthermore, analysis of publicly available gene expression datasets identified that decreased production of ceramides and increased accumulation of sphingoid base intermediates by metabolic enzymes were associated with better survival outcomes in TNBC patients. Our LC-MS lipidomics profiling of TNBC tumors has, for the first time, identified sphingomyelins as a potential prognostic marker and implicated enzymes involved in sphingolipid metabolism as candidate therapeutic targets that warrant further investigation.

SUBMITTER: Purwaha P

PROVIDER: S-EPMC6161031 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Unbiased Lipidomic Profiling of Triple-Negative Breast Cancer Tissues Reveals the Association of Sphingomyelin Levels with Patient Disease-Free Survival.

Purwaha Preeti P Gu Franklin F Piyarathna Danthasinghe Waduge Badrajee DWB Rajendiran Theckelnaycke T Ravindran Anindita A Omilian Angela R AR Jiralerspong Sao S Das Gokul G Morrison Carl C Ambrosone Christine C Coarfa Cristian C Putluri Nagireddy N Sreekumar Arun A

Metabolites 20180713 3

The reprogramming of lipid metabolism is a hallmark of many cancers that has been shown to promote breast cancer progression. While several lipid signatures associated with breast cancer aggressiveness have been identified, a comprehensive lipidomic analysis specifically targeting the triple-negative subtype of breast cancer (TNBC) may be required to identify novel biomarkers and therapeutic targets for this most aggressive subtype of breast cancer that still lacks effective therapies. In this c ...[more]

PMID: 30011843

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Project description:BackgroundNeoadjuvant chemotherapy (NACT) is considered a standard treatment strategy for locally advanced triple negative breast cancer (TNBC). TNBC patients who achieve a pathologic complete response (pCR) are predicted to have a better prognosis while unfavorable chemo-sensitivity is still associated with a higher risk of disease relapse. The objective of this study was to construct a nomogram to predict disease-free survival (DFS) for TNBC patients following NACT.MethodsA total of 165 TNBC patients who underwent standard NACT and surgery were retrospectively reviewed, and data on their clinicopathological factors before and after NACT were collected. Independent prognostic factors for DFS were identified by Cox regression based on lower Akaike information criteria (AIC) and Bayesian information criterion (BIC). A nomogram to predict the 2-year and 5-year DFS following NACT for TNBC was constructed based on training cohort (n = 132) and validated by a validation cohort (n = 33).ResultsEither limited or full pCR (breast-only pCR, node-only pCR, or both-pCR) indicated significantly improved DFS and overall survival (OS) (p < 0.001). Lager residual tumor size (hazard ratio [HR] 1.175, p = 0.011) and the presence of lymphatic vessel invasion (LVI) (HR 3.168, p = 0.001) were identified as independent predictors of disease relapse in the training cohort. Five variables, including age, primary tumor size, histological grade, residual tumor size, and LVI were used to establish the nomogram. The C-index of the nomogram was 0.815, and calibration curves showed an acceptable consistency between the actual and nomogram-predicted 2-year and 5-year DFS. The proposed nomogram demonstrated superior predictive performance compared with Residual Cancer Burden (RCB) classification and the 8th American Joint Committee on Cancer Post Neoadjuvant Therapy Classification (AJCC ypTNM) staging system (area under the curve [AUC] for 2-year DFS: 0.870 vs. 0.758 vs. 0.711, respectively; AUC for 5-year DFS: 0.794 vs. 0.731 vs. 0.702, respectively) in the validation cohort.ConclusionsThe nomogram proposed in our study enabled to quantify the risk of disease relapse and demonstrated superior predictive performance than a survival predict instrument. It was an easy-to-use tool for clinicians to guide individualized surveillance of TNBC patients following standard NACT.

Project description:Introduction:Triple-negative breast cancer (TNBC) is a group of breast carcinoma characterized by the lack of expression of estrogen and progesterone hormone receptors (ER, PgR) and HER2. This form is also characterized by its aggressiveness, a low survival rate, and the absence of targeted therapies. This study was planned to evaluate the clinical features, treatment, and prognosis characteristics of TNBC in a population of Moroccan patients. Methods:In this retrospective study, a total of 905 patients diagnosed with breast cancer at the National Institute of Oncology in Rabat, Morocco, have been included. Based on molecular subtype, patients were divided into 2 categories: TNBC and non-TNBC patients. Data were recorded from patients' medical files and analyzed using SPSS 13.0 software (IBM). Results:Overall, 17% of the patients had TNBC. At diagnosis, the median age of TNBC cases was 47?years, with extreme ages of 40 and 55?years. The median follow-up time was 30?months (10-53?months) and the 3-year survival rate was 76%. No significant difference was observed among the patients in terms of age at diagnosis, age at menarche, age at the time of first birth, nulliparity, oral contraception, and family history of breast cancer. Menopausal status and the number of pregnancy were significantly higher in the non-TNBC group. The percentage of grade 3 (G3) tumors was higher in the TNBC group (P?<?.001). Using neoadjuvant, adjuvant chemotherapy and radiotherapy, a net benefit in the event-free survival was registered for the 2 groups. Conclusions:This retrospective study was very informative and showed that women with TNBC had a less favorable prognosis than non-TNBC cases. Clinical data demonstrated that risk factors including age, premenopausal status, parity, hormonal contraceptive use, advanced disease, and a high histologic grade were independently associated with TNBC. However, large tumors and high Scarff-Bloom and Richardson grade prevail in TNBC cases with a higher incidence of lymph node metastases.

Dataset Information

Unbiased Lipidomic Profiling of Triple-Negative Breast Cancer Tissues Reveals the Association of Sphingomyelin Levels with Patient Disease-Free Survival.

Publications

Unbiased Lipidomic Profiling of Triple-Negative Breast Cancer Tissues Reveals the Association of Sphingomyelin Levels with Patient Disease-Free Survival.

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