Breast Cancer Metabolism in Association with Diabetes and Stress
General Information Short Title: Breast Cancer Metabolism in Association with Diabetes and Stress Document Type: Notice of Intent Solicitation Number: 75N91020R00025 Posted Date: 5/8/2020 Response Dat... General Information Short Title: Breast Cancer Metabolism in Association with Diabetes and Stress Document Type: Notice of Intent Solicitation Number: 75N91020R00025 Posted Date: 5/8/2020 Response Date: 5/18/2020 Classification Code: B599 – Special Studies/ Analysis - Other NAICS Code: 541690 – Other Scientific and Technical Consulting Services Contracting Office Address Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Office of Acquisitions, 9609 Medical Center Drive, Room 1E232 Bethesda, MD 20892, UNITED STATES The National Cancer Institute (NCI), Center for Cancer Research (CCR), Laboratory of Human Carcinogenesis, Molecular Epidemiology Section plans to procure metabolomics analytical services, on a sole source basis from Metabolon. This acquisition will be processed under FAR Part 12 – Acquisition for Commercial items and will be made pursuant to the authority in FAR 13.106-1(b)(1) using simplified acquisition procedures for commercial items. The North American Industry Classification System code is 541690 and the business size standard is 1,000 employees. Only one award will be made as a result of this solicitation. This will be awarded as a Non-Severable) firm fixed price type contract. It has been determined there are no opportunities to acquire green products or services for this procurement. OBJECTIVE In previous studies, fifty-two fresh-frozen human breast tumors and 40 cell pellets were obtained from 5 human breast cancer cell lines and analyzed for changes in cell metabolism associated with diabetes. Cell lines were treated with high glucose to mimic diabetes in cell culture. Recent clinical studies showed that co-morbidities like diabetes affect breast cancer outcomes and can decrease patient survival, indicating that diabetes affects the metabolism of breast tissues. In an analysis of the Maryland breast cancer patient cohort, the National Cancer Institute (NCI), Center for Cancer Research, (CCR) had found that women with a diabetes diagnosis have decreased breast cancer-specific survival and alteration in tumor metabolism, indicating that diabetes affects tumor biology. It is quite plausible that diabetes-induced changes in insulin signaling and metabolism worsen tumor biology, but these effects had not been previously investigated. Diabetes-related metabolic changes in breast cancer cell lines were compared with those in breast tumors. STUDY 1: A total of 66 fresh-frozen breast tissues/cell lines will be analyzed to examine how diabetes may affect the metabolism of human breast tumors. For this study, CCR grew human breast cancer cell lines in mice from closely related strains that have or do not have diabetes as a co-morbidity, allowing for the study of the effect of diabetes on metabolism and tumor biology in a controlled experimental setting. In addition, CCR will analyze human breast tumors and adjacent non-cancerous breast tissue from patients with diabetes. This study is a continuation of two previous projects with Metabolon in which CCR studied the metabolism of 1) breast tumors from patients with and without diabetes and 2) human breast cancer cell lines that grow in high versus low glucose cell culture medium to mimic the effects of diabetes. The goal of this study is to combine the analysis results from the two previous projects and this current study to obtain a more complete picture of how diabetes affects breast cancer in human patients and experimental models to obtain robust findings that are common to all datasets and best describe the diabetes-related breast cancer biology and how it may affect disease progression and response to current standard cancer therapy. Recent clinical studies showed that co-morbidities like diabetes affect breast cancer outcomes and can decrease patient survival, indicating that diabetes affects the metabolism of breast tissues. In an earlier analysis of our Maryland breast cancer patient cohort, CCR had found that women with a diabetes diagnosis have decreased breast cancer-specific survival and alteration in tumor metabolism indicating that diabetes affects tumor biology through metabolism. It is quite plausible that diabetes-induced changes in insulin signaling and metabolism worsen tumor biology, but these effects have not been previously investigated. With the current experiments, CCR will compare diabetes-related metabolic changes in breast cancer xenografts that grew in mammary fat pads of mice from closely related strains that have or do not have diabetes as a co-morbidity. STUDY 2: This study evaluates the role of environmentally-induced stress signaling and co-morbidities in breast cancer progression. CCR started projects studying the impact of stressful life events and diabetes on tumor biology, using one comprehensive approach to elucidate the effect of these exposures on breast cancer metabolism. In a clinical study, breast cancer patients who were scheduled for breast cancer surgery received a short survey evaluating their perceived stress and social isolation status. CCR also collected frozen tumor and adjacent normal breast tissue and blood samples from these patients to evaluate whether the breast tissue or the blood samples have a biological signature related to their perceived stress and social isolation status. CCR hypothesizes that patients with a high perceived stress exposure have a biological signature consistent with a more aggressive disease and poorer survival. The pilot study is designed to collect 100 tumor/normal pairs from consented patients with a completed survey. In the present study, CCR will analyze 42 breast tumors and 41 adjacent non-cancerous breast tissues from patients with stress exposure data. The contractor will also merge the new dataset with older datasets that CCR previously received from Metabolon. This is essential for this project. The contractor offers this service at no additional charges, allowing for comparison of diabetes study-related findings with stress study-related findings. SCOPE The Molecular Epidemiology Section will provide the contractor with 11-60 mg of frozen breast tissue. The tissues will first be pulverized, and then processed using methanol in water for the extraction of metabolites. Extracted samples must be run on Ultraperformance Liquid Chromatography coupled to tandem Mass Spectrometry (UPLC-MS/MS) as well as Gas Chromatography coupled to Mass Spectrometry (GC-MS) by the contractor. Contractor will quantitatively measure metabolite abundance in tissue extracts and confirm metabolite identities with standards. The contractor must have access to a large in-house library of known and identified molecules, against which any detected metabolites in a sample can be compared. The contractor additionally must have the software that can deconvolute the metabolomics data in such way that they can cluster together fragments from the same molecule that will be reported as one metabolite rather as multiple metabolites when reported back in a data spreadsheet format. This function of the software will enable to reduce the amount of noise that this type of data can carry with it. The Contractor will provide relative quantitation values for all the metabolites with confirmed identities but also unknowns. The identified metabolites will be confirmed against the Contractor’s in-house generated authentic standard library that includes retention time, molecular weight (m/z), preferred adducts, and in-source fragments as well as their associated MS/MS spectra for all molecules in the library. The Contractor will provide spectra of standards for publication if requested. CONTRACT REQUIREMENTS/ AND PERSONNEL QUALIFICATIONS The contractor will be profiling the metabolome of 93 human fresh-frozen breast tissues, 40 Xenograft tissues and 16 cell line pellets. The contractor will receive the samples, process the samples, and measure metabolites in the extracts using state of the art mass spectrometry equipment. Contractor will measure at least 1000 metabolites across all major classes. Covered classes should include amino acids, carbohydrates, lipids, nucleotides, microbiota metabolism, energy, cofactors & vitamins, xenobiotics, and novel metabolites. This large number of metabolites is required. Otherwise our group cannot reliably deduce what metabolic processes are affected by diabetes in breast cancer biology. The contractor will identify and quantitate metabolites across all classes of metabolites with less than 5% process variability and will provide a report and datasheet back to the customer that contain QC measurements and the standardized relative abundance values of these metabolites for all 149 samples (for further analysis at the NCI). The contractor will also merge the new dataset with older datasets that we previously received from Metabolon. This is essential for this project. The contractor offers this service at no additional charges, allowing CCR to compare diabetes study-related findings with stress study-related findings. TYPE OF ORDER This will be issued as a non-severable firm fixed price purchase order. PERIOD OF PERFORMANCE The period of performance is from June 1, 2020 to August 31, 2020. PLACE OF PERFORMANCE Metabolon 617 Davis Drive, Suite 100 Morrisville, NC 27560 US REPORT(S)/DELIVERABLES AND DELIVERY SCHEDULE Data will be communicated in such a way that molecules detected in the tissues will be identified against an in-house library and will be sent in a report back to the Molecular Epidemiology Section, Laboratory of Human Carcinogenesis, in an Excel sheet for further analysis. Excel sheet will contain sample IDs and standardized relative abundance of the about 1000 metabolites for each sample. 1. A relative concentration profile of all structurally named small-molecule entities, which can include both endogenous compounds, xenobiotics, and their metabolites, extracted from the samples and detected by our HD4 Global Metabolomics platform (Excel file). 2. An outline of the analytical methods is provided in Appendix form (Word report). 3. Access to the MetaboLync Client Portal for downloading the study deliverables (Word report, Excel data file). Standard Turnaround Time 8 - 12 weeks from receipt of samples and necessary information. These projects are a continuation of project NCIA-01-16ML that were completed with Metabolon in which NCI compared the metabolome of breast tumors from women with and without diabetes. NCIA-01-16ML revealed that there is a distinct metabolite pattern in breast tumors associated with a diabetes diagnosis. To compare this new data studying xenograft tumors from mice that have or do not have diabetes as a co-morbidity (study 1) and the effects of stress exposures to breast cancer metabolism (study 2) it is only feasible to use the same platform as previously used with the breast tumors to maintain consistency. The contractor will be profiling the metabolome of 93 human fresh-frozen breast tissues, 40 Xenograft tissues and 16 cell line pellets. The contractor will receive the samples, process the samples, and measure metabolites in the extracts using state of the art mass spectrometry equipment. The contractor will measure at least 1000 metabolites across all major classes. Covered classes should include amino acids, carbohydrates, lipids, nucleotides, microbiota metabolism, energy, cofactors & vitamins, xenobiotics, and novel metabolites. This large number of metabolites is required, otherwise NCI cannot reliably deduce what metabolic processes are affected by diabetes in breast cancer biology. The contractor will identify and quantitate metabolites across all classes of metabolites with less than 5% process variability and will provide a report and datasheet back to the customer that contain QC measurements and the standardized relative abundance values of these metabolites for all 149 samples (for further analysis at the NCI). The contractor will also merge the new dataset with older datasets that we previously received from Metabolon. This is essential for this project. The contractor offers this service at no additional charges allowing us to compare diabetes study-related findings (study 1) with stress study-related findings (study 2). This notice is not a request for competitive quotation. However, if any interested party, especially small businesses, believes it can meet the above requirement, it may submit a capability statement, proposal, or quotation, which shall be considered by the agency. The statement of capabilities and any other information furnished must be in writing and must contain material in sufficient detail to allow NCI to determine if the party can perform the requirement. Responses must be received in the contracting office by 12:00 PM EST, on May 18, 2020. All responses and questions must be emailed to David Romley, Contract Specialist via electronic mail at david.romley@nih.gov. A determination by the Government not to compete this proposed requirement based upon responses to this notice is solely within the discretion of the Government. Information received will be considered solely for the purpose of determining whether to conduct a competitive procurement. No collect calls will be accepted. In order to receive an award, contractors must be registered and have valid certification in the System for Award Management (SAM) through sam.gov. Reference: 75N91020R00025 on all correspondence.
Data sourced from SAM.gov.
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