Project description:Lung cancer is the leading cause of cancer mortality and early detection is the key to improve survival. However, there are no reliable blood-based tests currently available for early-stage lung cancer diagnosis. Here, we performed single-cell RNA sequencing of early-stage lung cancer and found lipid metabolism was broadly dysregulated in different cell types and glycerophospholipid metabolism is the most significantly altered lipid metabolism-related pathway. Untargeted lipidomics were detected in an exploratory cohort of 311 participants. Through support vector machine algorithm-based and mass spectrum-based feature selection, we have identified nine lipids as the most important detection features and developed a LC-MS-based targeted assay utilizing multiple reaction monitoring. This target assay achieved 100.00% specificity on an independent validation cohort. In a hospital-based lung cancer screening cohort of 1036 participants examined by low dose CT and a prospective clinical cohort containing 109 participants, this assay reached over 90.00% sensitivity and 92.00% specificity. Accordingly, matrix-assisted laser desorption/ionization-mass spectrometry imaging assay confirmed the selected lipids were differentially expressed in early-stage lung cancer tissues in situ. Thus, this method, designated as Lung Cancer Artificial Intelligence Detector (LCAID), may be used for early detection of lung cancer or large-scale screening of high-risk populations in cancer prevention.
Project description:Lung cancer is the leading cause of cancer mortality and early detection is the key to improve survival. However, there are no reliable blood-based tests currently available for early-stage lung cancer diagnosis. Here, we performed single-cell RNA sequencing of early-stage lung cancer and found lipid metabolism was broadly dysregulated in different cell types and glycerophospholipid metabolism is the most significantly altered lipid metabolism-related pathway. Untargeted lipidomics were detected in an exploratory cohort of 311 participants. Through support vector machine algorithm-based and mass spectrum-based feature selection, we have identified nine lipids as the most important detection features and developed a LC-MS-based targeted assay utilizing multiple reaction monitoring. This target assay achieved 100.00% specificity on an independent validation cohort. In a hospital-based lung cancer screening cohort of 1036 participants examined by low dose CT and a prospective clinical cohort containing 109 participants, this assay reached over 90.00% sensitivity and 92.00% specificity. Accordingly, matrix-assisted laser desorption/ionization-mass spectrometry imaging assay confirmed the selected lipids were differentially expressed in early-stage lung cancer tissues in situ. Thus, this method, designated as Lung Cancer Artificial Intelligence Detector (LCAID), may be used for early detection of lung cancer or large-scale screening of high-risk populations in cancer prevention.
Project description:The paper describes a model on the detection of cancer based on cancer and immune biomarkers.
Created by COPASI 4.25 (Build 207)
This model is described in the article:
Improving cancer detection through combinations of cancer and immune biomarkers: a modelling approach
Raluca Eftimie and and Esraa Hassanein
J Transl Med (2018) 16:73
Abstract:
Background: Early cancer diagnosis is one of the most important challenges of cancer research, since in many can- cers it can lead to cure for patients with early stage diseases. For epithelial ovarian cancer (which is the leading cause of death among gynaecologic malignancies) the classical detection approach is based on measurements of CA-125 biomarker. However, the poor sensitivity and specificity of this biomarker impacts the detection of early-stage cancers.
Methods: Here we use a computational approach to investigate the effect of combining multiple biomarkers for ovarian cancer (e.g., CA-125 and IL-7), to improve early cancer detection.
Results: We show that this combined biomarkers approach could lead indeed to earlier cancer detection. However, the immune response (which influences the level of secreted IL-7 biomarker) plays an important role in improving and/or delaying cancer detection. Moreover, the detection level of IL-7 immune biomarker could be in a range that would not allow to distinguish between a healthy state and a cancerous state. In this case, the construction of solu- tion diagrams in the space generated by the IL-7 and CA-125 biomarkers could allow us predict the long-term evolu- tion of cancer biomarkers, thus allowing us to make predictions on cancer detection times.
Conclusions: Combining cancer and immune biomarkers could improve cancer detection times, and any predic- tions that could be made (at least through the use of CA-125/IL-7 biomarkers) are patient specific.
Keywords: Ovarian cancer, Mathematical model, CA-125 biomarker, IL-7 biomarker, Cancer detection times
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Project description:Owing to the lack of effective screening tools and early detection biomarkers, ovarian cancer (OC) still remains as a deadly disease with highest mortality among other gynecological cancers. So far there have been no attempts to discover biomarkers using early stage OC patients. MicroRNAs (miRNAs) have been recognized as great tool to develop non-invasive biomarkers in various cancers including ovarian cancer.
Project description:Prostate cancer is the second most common cancer in men and affects 1 in 9 men in the United States. Early screening for prostate cancer often involves monitoring levels of prostate-specific antigen (PSA) and performing digital rectal exams. However, a prostate biopsy is always required for definitive cancer diagnosis. The Early Detection Research Network (EDRN) is a consortium within the National Cancer Institute aimed at improving screening approaches and early detection of cancers. As part of this effort, the Weill Cornell EDRN Prostate Cancer has collected and biobanked specimens from men undergoing a prostate biopsy between 2008 and 2017. In this report, we describe blood metabolomics measurements for a subset of this population. The dataset includes detailed clinical and prospective records for 580 patients who underwent prostate biopsy, 287 of which were subsequentially diagnosed with prostate cancer, combined with profiling of 1,482 metabolites from plasma samples collected at the time of biopsy. We expect this dataset to provide a valuable resource for scientists investigating prostate cancer metabolism.
Project description:Recent computed tomography (CT) screening trials showed that it is effective for early detection of lung cancer, but were plagued by high false positive rates. Additional blood biomarker tests designed to complement CT screening and reduce false positive rates are highly desirable. In the current study, we expand upon our initial experimental findings as part of the discovery phase by evaluating metabolites in serum from subjects with benign or malignant SPNs using a combined approach of gas chromatography time-of-flight mass spectrometry (GC-TOFMS) and hydrophilic liquid chromatography accurate mass quadrupole time-of-flight mass spectrometry (HILIC-qTOFMS). Furthermore, we evaluated serum collected pre-diagnosis and at-diagnosis of lung cancer in addition to samples obtained post-surgical intervention from subjects with malignant SPNs (post-diagnosis). We hypothesize that our systems biology approach to identify candidate metabolomics biomarkers will ultimately lead to improved early detection of lung cancer and can be used in as a companion blood test to LDCT screening.
Project description:Recent computed tomography (CT) screening trials showed that it is effective for early detection of lung cancer, but were plagued by high false positive rates. Additional blood biomarker tests designed to complement CT screening and reduce false positive rates are highly desirable. In the current study, we expand upon our initial experimental findings as part of the discovery phase by evaluating metabolites in serum from subjects with benign or malignant SPNs using a combined approach of gas chromatography time-of-flight mass spectrometry (GC-TOFMS) and hydrophilic liquid chromatography accurate mass quadrupole time-of-flight mass spectrometry (HILIC-qTOFMS). Furthermore, we evaluated serum collected pre-diagnosis and at-diagnosis of lung cancer in addition to samples obtained post-surgical intervention from subjects with malignant SPNs (post-diagnosis). We hypothesize that our systems biology approach to identify candidate metabolomics biomarkers will ultimately lead to improved early detection of lung cancer and can be used in as a companion blood test to LDCT screening.
Project description:Colorectal cancer is the third most common malignancy and the fourth most common cause of cancer mortality worldwide. In 2008, more than one million cases were newly diagnosed, and more than 600,000 people died from the disease. Given its slow development from removable precancerous lesions and curable early stages, screening for CRC has the potential to reduce both the incidence and mortality of the disease. However, compliance with current screening methods remains poor and there is a clear need for an accurate in vitro blood test to increase participation in colorectal cancer screening. In this study, we performed genome-wide gene expression profiling of peripheral blood samples from 100 healthy controls and 100 colorectal cancer patients using PAXgeneTM technology and Affymetrix GeneChip® microarrays. We show that monitoring gene expression in blood results in distinct transcriptional profiles between the controls and cancer patients. Thus, the microarray-based blood gene expression profiling holds great promise for developing novel biomarkers for colorectal cancer detection.
Project description:Aim is to identify a panel of m/z markers for the early detection of colorectal cancer (CRC). Identification of a molecular pattern that can distinguish the primary tumours of colorectal cancer with lymph node metastasis compared to those without. Materials and Methods: Using MALDI MSI data, we developed and validated a machine learning model that can be used for early screening of CRC. Our model yields high sensitivity and specificity in distinguishing normal tissue from the cancerous. Model described here, can be a used in clinical labs for early diagnosis of colorectal cancer
Project description:To identify a panel of m/z markers for the early detection of colorectal cancer (CRC). Identication of a molecular pattern that can distinguish the primary tumours of colorectal cancer with lymph node metastasis compared to those without. Using MALDI MSI data,we developed and validated a machine learning model that can be used for early screening of CRC. Our model yields high sensitivity and specicity in distinguishing normal tissue from the cancerous. Model described here, can be a used in clinical labs for early diagnosis of colorectal cancer.