Liquid Biopsy For Early Detection Research Articles

Transcriptomics-Based Liquid Biopsy for Early Detection of Recurrence in Locally Advanced Gastric Cancer.

The study presents a transcriptomics-based liquid biopsy approach for early recurrence detection in locally advanced gastric cancer (LAGC). Four mRNA biomarkers (AGTR1, DNER, EPHA7, and SUSD5) linked to recurrence are identified through transcriptomic data analysis. A Risk Stratification Assessment (RSA) model combining these biomarkers with clinical features showed superior predictive accuracy for postoperative recurrence, with AUCs of 0.919 and 0.935 in surgical and liquid biopsy validation cohorts, respectively. Functional studies using human gastric cancer cell lines AGS and HGC-27 demonstrated that silencing the identified mRNA panel genes impaired cell migration, invasion, and proliferation. In vivo experiments further showed reduced tumor growth, metastasis, and lymphangiogenesis in mice, possibly mediated by the cAMP signaling pathway. This non-invasive approach offers significant potential for enhancing recurrence detection and enabling personalized treatment strategies, thereby improving patient outcomes in the management of LAGC.

Abstract 1071: Circulation of rare events in the liquid biopsy for early detection of lung mass lesions

Abstract Lung cancer screening with low-dose CT scans (LDCT) has reduced mortality for patients with high-risk smoking histories. However, this method of screening remains imperfect. High rates of false positive scans expose patients to additional morbidity as they pursue subsequent diagnostic evaluation. Real-world application of screening LDCT remains low. Finally, current screening guidelines exclude those without smoking histories, a population which comprises up to a quarter of lung cancer patients. We sought to explore the utility of liquid biopsy (LBx) in lung cancer patients and its use in early cancer screening and diagnosis. Using the third generation High-Definition Single Cell Assay (HDSCA3.0) workflow, we analyzed 99 peripheral blood samples divided into three cohorts: Normal Donors (ND, n=50) who were healthy volunteers with no known pathology, Screening CT patients (CT, n=25) who underwent standard LDCT screening with resultant Lung-RADS 1-2, Biopsy patients (BX, n=24) who had abnormal CT scans requiring tissue biopsy. The ND group was used to characterize baseline epithelial, mesenchymal, endothelial, and immune cells, alongside acellular events (oncosomes). For the CT and BX patients, demographic information including age, gender, and average BMI was roughly equivalent, however average pack-years smoked differed owing to 10 (42%) patients in the BX group who had no prior smoking history. A total of 14 (58%) BX patients were diagnosed with primary lung cancer (BX+), of which 11(75%) were adenocarcinoma, 2 (19%) were squamous cell carcinoma and 1 (6%) was small cell. Across the cohorts we observed intra- and interpatient heterogeneity of rare events including multiple phenotypic rare cell populations and oncosomes. The comparison of the rare event enumerations between the ND, CT, BX+, and BX- cohorts revealed a greater incidence of total events, total rare cells and oncosomes, as well as specific cellular phenotypes in the CT and BX cohorts compared to the ND cohort. LBx analytes were detected at a significant elevation in the BX samples compared to the CT samples, but there was no significant difference between BX+ and BX- samples. The data supports the utility of the LBx in distinguishing patients with an alveolar mass lesion from those without, providing a mechanism for screening prior to LDCT to better inform clinical workup and avoid unnecessary radiation exposure and biopsy. Citation Format: Anya Shah, Karen Resnick, Jeremy Mason, Peter Kuhn, Jorge Nieva, Stephanie Shishido. Circulation of rare events in the liquid biopsy for early detection of lung mass lesions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1071.

Liquid biopsy for early detection of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly prevalent and lethal cancer globally. Over 90% of HCC cases arise in the context of liver cirrhosis, and the severity of the underlying liver disease or advanced tumor stage at diagnosis significantly limits treatment options. Early diagnosis is crucial, and all guidelines stress the importance of screening protocols for HCC early detection as a public health objective. As serum biomarkers are not optimal for early diagnosis, liquid biopsy has emerged as a promising tool for diagnosis, prognostication, and patients' stratification for personalized therapy in various solid tumors, including HCC. While circulating tumor cells (CTCs) are better suited for personalized therapy and prognosis, cell-free DNA (cfDNA) and extracellular vesicle-based technologies show potential for early diagnosis, HCC screening, and surveillance protocols. Evaluating the added value of liquid biopsy genetic and epigenetic biomarkers for HCC screening is a key goal in translational research. Somatic mutations commonly found in HCC can be investigated in cfDNA and plasma exosomes as genetic biomarkers. Unique methylation patterns in cfDNA or cfDNA fragmentome features have been suggested as innovative tools for early HCC detection. Likewise, extracellular vesicle cargo biomarkers such as miRNAs and long non-coding RNAs may serve as potential biomarkers for early HCC detection. This review will explore recent findings on the utility of liquid biopsy for early HCC diagnosis. Combining liquid biopsy methods with traditional serological biomarkers could improve the overall diagnostic accuracy for early HCC detection.

Altered plasma metabolite levels can be detected years before a glioma diagnosis.

Genetic and metabolic changes in tissue and blood are reported to occur several years before glioma diagnosis. Since gliomas are currently detected late, a liquid biopsy for early detection could affect the quality of life and prognosis of patients. Here, we present a nested case-control study of 550 prediagnostic glioma cases and 550 healthy controls from the Northern Sweden Health and Disease study (NSHDS) and the European Prospective Investigation into Cancer and Nutrition (EPIC) study. We identified 93 significantly altered metabolites related to glioma development up to 8 years before diagnosis. Out of these metabolites, a panel of 20 selected metabolites showed strong disease correlation and a consistent progression pattern toward diagnosis in both the NSHDS and EPIC cohorts, and they separated future cases from controls independently of biological sex. The blood metabolite panel also successfully separated both lower-grade glioma and glioblastoma cases from controls, up to 8 years before diagnosis in patients within the NSHDS cohort and up to 2 years before diagnosis in EPIC. Pathway enrichment analysis detected metabolites related to the TCA cycle, Warburg effect, gluconeogenesis, and cysteine, pyruvate, and tyrosine metabolism as the most affected.

Aberrant circulating tumor DNA methylation and exosomal microRNA biomarkers for early detection of colorectal cancer.

Colorectal cancer (CRC) became the third most commonly diagnosed malignancy and the second leading cause of cancer death in 2020. However, the rates of early screening and early diagnosis for CRC remain unsatisfactory. Thus, it is essential to explore the initiating factors of CRC and strategies for its early diagnosis. Research progress in liquid biopsy has led to the finding that circulating tumor-derived DNA (ctDNA) and exosomes play vital roles in early detection of CRC. THE APPLICATIONS OF LIQUID BIOPSY FOR EARLY DETECTION OF COLORECTAL CANCER: Moreover, the increased understanding of epigenetics has highlighted the role of ctDNA methylation in CRC carcinogenesis, and the detection of aberrant ctDNA methylation markers is a feasible strategy for diagnosis of early-stage CRC. Among exosomal markers, microRNAs (miRNAs) are abundant and are the most researched. Upregulated or downregulated expression of exosome-derived miRNAs can indicate the occurrence of early-stage CRC. The current research progress on aberrant ctDNA methylation and tumor exosomal miRNA biomarkers in early detection of CRC is summarized in this review, and the advantages and shortcomings of the methods are discussed.

P19 Detection of HPV16 cell-free DNA in liquid biopsies for early detection of HPV-OPC

P19 Detection of HPV16 cell-free DNA in liquid biopsies for early detection of HPV-OPC

Small extravesicular microRNA in head and neck squamous cell carcinoma and its potential as a liquid biopsy for early detection.

The objective was to assess secretion of small extracellular vesicular microRNA (exo-miRNA) in head and neck squamous cell carcinoma (HNSCC) according to human papillomavirus (HPV) status, and determine the translational potential as a liquid biopsy for early detection. This study employed a combination of cell culture and case-control study design using archival pretreatment serum. Small extracellular vesicles (sEV) were isolated from conditioned culture media and human serum samples via differential ultracentrifugation. miRNA-sequencing was performed on each sEV isolate. There were clear exo-miRNA profiles that distinguished HNSCC cell lines from nonpathologic oral epithelial control cells. While there was some overlap among profiles across all samples, there were apparent differences in exo-miRNA profiles according to HPV-status. Importantly, differential exo-miRNA profiles were also apparent in serum from early-stage HNSCC cases relative to cancer-free controls. Our findings indicate that exo-miRNA are highly dysregulated in HNSCC and support the potential of exo-miRNA as biomarkers for HNSCC.

Liquid biopsy for early detection and therapeutic monitoring of hepatocellular carcinoma.

Advances in our knowledge of the molecular characteristics of hepatocellular carcinoma (HCC) have enabled significant progress in the detection and therapeutic prediction of HCC. As a non-invasive alternative to tissue biopsy, liquid biopsy examines circulating cellular components such as exosomes, nucleic acids, and cell-free DNA found in body fluids (e.g., urine, saliva, ascites, and pleural effusions) and provides information about tumor characteristics. Technical advances in liquid biopsy have led to the increasing adoption of diagnostic and monitoring applications for HCC. This review summarizes the various analytes, ongoing clinical trials, and case studies of United States Food and Drug Administrationapproved in vitro diagnostic applications for liquid biopsy, and provides insight into its implementation in managing HCC.

EP11.01-011 Clinical Application of Liquid Biopsy for Assessing Early EGFR Mutation Detection in Non-Small Cell Lung Carcinoma

Liquid biopsy has already entered clinical practice in non-small cell lung carcinoma (NSCLC) patient care by means of analysing cell-free DNA (cfDNA) for detection of EGFR resistance mutations due to low success rate of repeat biopsy in NSCLC patients. However, being minimally invasive the use of liquid biopsy for early detection of EGFR mutation in treatment naïve patients is less explored.

Abstract 5922: Clinical validation of a spectroscopic liquid biopsy for early detection of brain cancer

Abstract Diagnostic delays impact the quality of life and survival of patients with brain tumors. Earlier and expeditious diagnoses in these patients are crucial to reducing the morbidities and mortalities associated with brain tumors. A simple, rapid blood test that can be administered easily in a primary care setting to efficiently identify symptomatic patients who are most likely to have a brain tumor would enable quicker referral to brain imaging for those who need it most. Blood serum samples from 603 patients were prospectively collected and analyzed. Patients either had non-specific symptoms that could be indicative of a brain tumor on presentation to the Emergency Department, or a new brain tumor diagnosis and referral to the neurosurgical unit, NHS Lothian, Scotland. Patient blood serum samples were analyzed using the Dxcover® Brain Cancer liquid biopsy. This technology utilizes infrared spectroscopy combined with a diagnostic algorithm to predict the presence of intracranial disease. Our liquid biopsy approach reported an area under the receiver operating characteristic curve of 0.8. The sensitivity-tuned model achieves a 96% sensitivity with 45% specificity (NPV 99.3%) and identified 100% of glioblastoma multiforme patients. When tuned for a higher specificity, the model yields sensitivity of 47% with 90% specificity (PPV 28.4%). This simple, non-invasive blood test facilitates the triage and radiographic diagnosis of brain tumor patients, while providing reassurance to healthy patients. Minimizing time to diagnosis would facilitate identification of brain tumor patients at an earlier stage, enabling more effective, less morbid surgical and adjuvant care. Citation Format: James M. Cameron, Paul M. Brennan, Georgios Antoniou, Holly J. Butler, Loren Christie, Justin J.A. Conn, Tom Curran, Ewan Gray, Mark G. Hegarty, Michael Jenkinson, Daniel Orringer, David S. Palmer, Alexandra Sala, Benjamin R. Smith, Matthew J. Baker. Clinical validation of a spectroscopic liquid biopsy for early detection of brain cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5922.

Cancer Biomarkers in Liquid Biopsy for Early Detection of Breast Cancer: A Systematic Review.

Breast cancer (BC) is the most common neoplasm in women worldwide. Liquid biopsy (LB) is a non-invasive diagnostic technique that allows the analysis of biomarkers in different body fluids, particularly in peripheral blood and also in urine, saliva, nipple discharge, volatile respiratory fluids, nasal secretions, breast milk, and tears. The objective was to analyze the available evidence related to the use of biomarkers obtained by LB for the early diagnosis of BC. Articles related to the use of biomarkers for the early diagnosis of BC due to LB, published between 2010 and 2022, from the databases (WoS, EMBASE, PubMed, and SCOPUS) were included. The MInCir diagnostic scale was applied in the articles to determine their methodological quality (MQ). Descriptive statistics were used, as well as determination of weighted averages of each variable, to analyze the extracted data. Sensitivity, specificity, and area under the curve values for specific biomarkers (individual or in panels) are described. In this systematic review (SR), 136 articles met the selection criteria, representing 17 709 patients with BC. However, 95.6% were case-control studies. In 96.3% of cases, LB was performed in peripheral blood samples. Most of the articles were based on microRNA (miRNA) analysis. The mean MQ score was 25/45 points. Sensitivity, specificity, and area under the curve values for specific biomarkers (individual or in panels) have been found. The determination of biomarkers through LB is a useful mechanism for the diagnosis of BC. The analysis of miRNA in peripheral blood is the most studied methodology. Our results indicate that LB has a high sensitivity and specificity for the diagnosis of BC, especially in early stages.

Cell-free DNA liquid biopsy for early detection of gastrointestinal cancers: A systematic review.

BACKGROUNDGastrointestinal tumors are among the most common cancer types, and early detection is paramount to improve their management. Cell-free DNA (cfDNA) liquid biopsy raises significant hopes for non-invasive early detection.AIMTo describe current applications of this technology for gastrointestinal cancer detection and screening.METHODSA systematic review of the literature was performed across the PubMed database. Articles reporting the use of cfDNA liquid biopsy in the screening or diagnosis of gastrointestinal cancers were included in the analysis.RESULTSA total of 263 articles were screened for eligibility, of which 13 articles were included. Studies investigated colorectal cancer (5 studies), pancreatic cancer (2 studies), hepatocellular carcinoma (3 studies), and multi-cancer detection (3 studies), including gastric, oesophageal, or bile duct cancer, representing a total of 4824 patients. Test sensitivities ranged from 71% to 100%, and specificities ranged from 67.4% to 100%. Pre-cancerous lesions detection was less performant with a sensitivity of 16.9% and a 100% specificity in one study. Another study using a large biobank demonstrated a 94.9% sensitivity in detecting cancer up to 4 years before clinical symptoms, with a 61% accuracy in tissue-of-origin identification. CONCLUSIONcfDNA liquid biopsy seems capable of detecting gastrointestinal cancers at an early stage of development in a non-invasive and repeatable manner and screening simultaneously for multiple cancer types in a single blood sample. Further trials in clinically relevant settings are required to determine the exact place of this technology in gastrointestinal cancer screening and diagnosis strategies.

Abstract 459: Lipidomic analysis of extracellular vesicles and its potential for the identification of body fluid-based biomarkers for breast cancer diagnosis

Abstract Background: Tumor-derived Extracellular Vesicles (EVs) are found in body fluids of cancer patients. These EVs include exosomes and microvesicles, which play an important role in tumor development and metastasis. Although EVs have great potential as liquid biopsies for early detection of breast cancer, the lipid composition of breast cancer-derived EVs is unknown. Here, we studied the lipid composition of EVs and its potential for the identification of body fluid-based biomarkers for breast cancer diagnosis. Methods: The lipid composition of EVs and their parental cells were evaluated for nine breast cancer and two non-cancerous mammary cell lines. EVs were isolated by size-exclusion chromatography (SEC). Furthermore, ten blood plasma samples were studied from women diagnosed with primary breast cancer before surgery, nine samples from patients with progressive metastatic breast cancer and ten samples from healthy women who neither had pre-existing medical conditions nor infections at the time the samples were collected or in the previous weeks. EVs were obtained from blood plasma samples by a combination of density gradient ultracentrifugation and SEC. Lipids were extracted from EVs and analyzed by reverse-phase liquid chromatography mass-spectrometry (LC-MS). Results: We found that EVs produced by breast cancer cell lines were enriched in sphingomyelins and ceramides when compared to their parental cells. Furthermore, phospholipids such as phosphatidylcholine and phosphatidylethanolamine were found to be abundant in these EVs. Multivariate analyses showed that EVs released by breast cancer cells can be distinguished from those released by non-cancerous cells based on their phospholipid and sphingolipid composition (AUCROC=0.99, p<0.001). A key finding of this study is that we also found significant differences in the phospholipid and sphingolipid composition between EVs found in blood plasma from breast cancer patients and healthy volunteers (AUCROC=0.99, p<0.001). Importantly with respect to the practical applications of this study for early diagnosis of breast cancer, these differences in EV's lipid content were also significant between EVs from primary breast cancer patients and healthy volunteers (AUCROC=0.99, p<0.001). Annotation of specific lipid species are currently being carried out by MS/MS analysis. Conclusion: Our findings demonstrate the potential of the lipid content of cancer-derived EVs for the identification of lipid biomarkers for breast cancer diagnosis and its use for the development of non-invasive (or minimally invasive) diagnostic methods based on blood plasma analysis. Citation Format: Erika Dorado, M Luisa Doria, Anika Nagelkerke, James S McKenzie, Stefania Maneta-Stavrakaki, Charlotte Ion, Thomas Whittaker, Jeremy Nicholson, Molly M Stevens, R Charles Coombes, Zoltan Takats. Lipidomic analysis of extracellular vesicles and its potential for the identification of body fluid-based biomarkers for breast cancer diagnosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 459.

The Potential of Aptamer-Mediated Liquid Biopsy for Early Detection of Cancer.

The early detection of cancer favors a greater chance of curative treatment and long-term survival. Exciting new technologies have been developed that can help to catch the disease early. Liquid biopsy is a promising non-invasive tool to detect cancer, even at an early stage, as well as to continuously monitor disease progression and treatment efficacy. Various methods have been implemented to isolate and purify bio-analytes in liquid biopsy specimens. Aptamers are short oligonucleotides consisting of either DNA or RNA that are capable of binding to target molecules with high specificity. Due to their unique properties, they are considered promising recognition ligands for the early detection of cancer by liquid biopsy. A variety of circulating targets have been isolated with high affinity and specificity by facile modification and affinity regulation of the aptamers. In this review, we discuss recent progress in aptamer-mediated liquid biopsy for cancer detection, its associated challenges, and its future potential for clinical applications.

Targeted proteomics-derived biomarker profile develops a multi-protein classifier in liquid biopsies for early detection of esophageal squamous cell carcinoma from a population-based case-control study

BackgroundEarly diagnosis of esophageal squamous cell carcinoma (ESCC) remains a challenge due to the lack of specific blood biomarkers. We aimed to develop a serum multi-protein signature for the early detection of ESCC.MethodsWe selected 70 healthy controls, 30 precancerous patients, 60 stage I patients, 70 stage II patients and 70 stage III/IV ESCC patients from a completed ESCC case-control study in a high-risk area of China. Olink Multiplex Oncology II targeted proteomics panel was used to simultaneously detect the levels of 92 cancer-related proteins in serum using proximity extension assay.ResultsWe found that 10 upregulated and 13 downregulated protein biomarkers in serum could distinguish the early-stage ESCC from healthy controls, which were validated by the significant dose-response relationships with ESCC pathological progression. Applying least absolute shrinkage and selection operator (LASSO) regression and backward elimination algorithm, ANXA1 (annexin A1), hK8 (kallikrein-8), hK14 (kallikrein-14), VIM (vimentin), and RSPO3 (R-spondin-3) were kept in the final model to discriminate early ESCC cases from healthy controls with an area under curve (AUC) of 0.936 (95% confidence interval: 0.899 ~ 0.973). The average accuracy rates of the five-protein classifier were 0.861 and 0.825 in training and test data by five-fold cross-validation.ConclusionsOur study suggested that a combination of ANXA1, hK8, hK14, VIM and RSPO3 serum proteins could be considered as a potential tool for screening and early diagnosis of ESCC, especially with the establishment of a three-level hierarchical screening strategy for ESCC control.

Cell-free DNA as a liquid biopsy for early detection of gastric cancer.

Gastric cancer (GC) is one of the most common malignant tumors with poor prognosis worldwide, mainly due to the lack of suitable modalities for population-based screening and early detection of this disease. Therefore, novel and less invasive tests with improved clinical utility are urgently required. The remarkable advances in genomics and proteomics, along with emerging new technologies for highly sensitive detection of genetic alterations, have shown the potential to map the genomic makeup of a tumor in liquid biopsies, in order to assist with early detection and clinical management. The present review summarize the current status in the identification and development of cell-free DNA (cfDNA)-based biomarkers in GC, and also discusses their potential utility and the technical challenges in developing practical cfDNA-based liquid biopsy for early detection of GC.

Precision Prevention and Cancer Interception: The New Challenges of Liquid Biopsy.

Despite major therapeutic progress, most advanced solid tumors are still incurable. Cancer interception is the active way to combat cancer onset, and development of this approach within high-risk populations seems a logical first step. Until now, strategies for the identification of high-risk subjects have been based on low-sensitivity and low-specificity assays. However, new liquid biopsy assays, "the Rosetta Stone of the new biomedicine era," with the ability to identify circulating biomarkers with unprecedented sensitivity, promise to revolutionize cancer management. This review focuses on novel liquid biopsy approaches and the applications to cancer interception. Cancer interception involves the identification of biomarkers associated with developing cancer, and includes genetic and epigenetic alterations, as well as circulating tumor cells and circulating epithelial cells in individuals at risk, and the implementation of therapeutic strategies to prevent the beginning of cancer and to stop its development. Large prospective studies are needed to confirm the potential role of liquid biopsy for early detection of precancer lesions and tumors.

Abstract IA19: Multiple uses of circulating tumor cells in lung cancer?

Abstract Liquid biopsies are increasingly being used in clinical studies as prognostic, predictive, and pharmacodynamics biomarkers, as surrogates of tumor response, to detect minimal residual disease after treatment with curative intent and to inform on mechanisms of treatment resistance and treatment switching. There is also steady progress in the development of liquid biopsies for early detection of cancers. The advantages of liquid biopsies are that they are minimally invasive and readily repeatable. The liquid biopsy that has been most widely adopted is circulating tumor DNA (ctDNA) as it is readily measured without specialist equipment in most molecular biology laboratories. Circulating tumor cells (CTCs) are technically more challenging and have yet to realize their full potential as biomarkers in clinic. However, CTC technology is constantly improving, and CTCs have several exciting applications beyond ctDNA that, once optimized, will assist personalized cancer medicine, including their use as cultures for real-time therapy testing and their utility, in some cancer types, to derive mouse models. I will discuss the use of CTCs from patients with lung cancer in this presentation. CTCs in both non-small cell lung cancer (NSCLC) and SCLC enumerated by CellSearch (EpCAM and cytokerin positive, CD45 negative) hold prognostic information. However, while CellSearch CTCs are scarce in NSCLC, most likely due to epithelial-to-mesenchymal transition (EMT) that leads to downrgulation of the EpCAM surface marker used to capture them for enumeration, they are prevalent in SCLC. Single CTC copy number analysis has led to the development of classifier that, with further validation studies, could predict response to chemotherapy alongside ctDNA analysis for therapy monitoring. We have exploited SCLC CTC prevalence to derive mouse models in immune-incompetent mice (termed CDX) that allow us to explore biology and test new therapeutics. I will also update on our research using our biobank of 46 CDX models, exploring inter and intratumoral heterogeneity. The most important aspect of this approach is the ability to generate pre- and post-therapy CDX models allowing interrogation of therapy resistance mechanisms and the biology of progressing disease in a tumor type where tumor evolution is rapid and where serial tumor biopsies are rarely obtained. I will also describe our approaches to study mechanisms of tumor dissemination, including vasculogenic mimicry and new models of brain metastasis. More recently, we are developing direct CTC cultures that may allow real-time therapy testing with reporting to the clinic. I will report on our NSCLC CTC studies within the UK TRACERx consortium to study tumor evolution. We have explored the potential of CTCs found in the pulmonary draining vein of stage I-IIIa patients at surgery with curative intent to predict risk of disease recurrence and shown in a case study that a lethal subclone that gives rise to metastasis 10 months later was identified in the pulmonary vein at surgery. In summary, this presentation will exemplify utility of CTCs in lung cancer that are distinct from but complement the implementation of ctDNA. Citation Format: Caroline Dive. Multiple uses of circulating tumor cells in lung cancer? [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA19.

Targeted Proteomics-Derived Biomarker Profile Develops a Multi-Protein Classifier in Liquid Biopsies for Early Detection of Esophageal Squamous Cell Carcinoma

Background: Early diagnosis of esophageal squamous cell carcinoma (ESCC) remains a challenge due to the lack of specific blood biomarkers. We aimed to develop a serum multi-protein signature for early detection of ESCC. Methods: We selected 70 healthy controls, 30 precancerous patients, 60 stage I patients, 70 stage II patients and 70 stage III/IV ESCC patients from a completed ESCC case-control study in a high-risk area of China. Olink Multiplex Oncology II targeted proteomics panel was used to simultaneously detect the levels of 92 cancer-related proteins in serum using proximity extension assay. Findings: We found that 10 upregulated and 13 downregulated protein biomarkers in serum could distinguish the early ESCC from healthy controls and their serum levels had significant dose-response relationships with ESCC progression. Applying least absolute shrinkage and selection operator (LASSO) regression and backward elimination algorithm, ANXA1 (annexin A1), hK8 (kallikrein-8), hK14(kallikrein-14), VIM (vimentin), and RSPO3 (R-spondin-3) were kept in final model to discriminate early ESCC cases from healthy controls with an area under curve (AUC) of 0.936 (95% confidence interval: 0.899~0.973). The average accuracy rates of the five-protein classifier were 0.861 and 0.825 in training and test data by five-fold cross-validation. Interpretation: Our study suggested that a combination of ANXA1, hK8, hK14, VIM and RSPO3 serum proteins could be considered as a potential tool for screening and early diagnosis of ESCC. Our results, however, need be confirmed in external case-control studies and prospective studies. Funding Statement: This work was supported by National Natural Science Foundation of China (81973116, 91846302, 81573229 and 81502870), National Key Research and Development program of China (2017YFC0907002 and 2017YFC0907003), International S&T Cooperation Program of China (2015DFE32790), European Research Council (682663), Medical and Health Technology Development Plan of Shandong Province (2018WS331). The funding sources had no role in the study design, interpretation of results, writing the manuscript or decision to submit the manuscript for the publication. The corresponding author has full access to all the data and assumes final responsibility for the decision to submit for publication. Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: The study protocol was approved by the Institutional Review Boards of the School of Life Sciences, Fudan University (date: February 19, 2009), Qilu Hospital, Shandong University (date: March 8, 2010), and Stockholm Ethical Vetting Board (2018/357-31). The study was carried out in accordance with the approved protocol, and all participants provided written informed consent.

Screening for ovarian cancer: is there still hope?

SummaryMainly diagnosed at advanced stage, ovarian cancer still remains the most lethal gynecological malignancy. Regarding screening and early detection, ovarian cancer poses particular challenges. To date, no screening test has been proven capable of leading to a mortality benefit. In this short review, we summarize and discuss the underlying literature on screening for ovarian cancer, focusing on average-risk, asymptomatic women as well as women at high risk. We also discuss the continuous advances and limits in liquid biopsies for early detection and screening of ovarian cancer.