Establishment of a Multi-Analyte Serum Biomarker Panel to Identify Lymph Node Metastases in Non-small Cell Lung Cancer

Borgia, Jeffrey A.; Basu, Sanjib; Faber, L. Penfield; Kim, Anthony W.; Coon, John S.; Kaiser-Walters, K. A.; Fhied, Cristina; Thomas, Sherene M.; Rouhi, Omid; Warren, William H.; Bonomi, Philip; Liptay, Michael J.

doi:10.1097/jto.0b013e3181982abf

Cited by 38 publications

(51 citation statements)

References 45 publications

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“…Patients treated with neoadjuvant chemoradiation or radiation therapy were excluded from the study. All patients in the NSCLC cohort underwent definitive resection of their primary tumor with systematic lymph node dissection, as we define elsewhere (12). All serum specimens from patients receiving anatomic resections were collected immediately before surgery and were, therefore, fasting.…”

Section: Patient Populationsmentioning

confidence: 99%

“…Univariate statistics. Descriptive statistics, receiver operator characteristic (ROC) parameters [including "area under the curve" (AUC), specificity, and sensitivity], and P values from Mann-Whitney U test with two comparator groups were obtained for the individual analytes using the SPSS statistical software version 15.0 (SPSS), as we previously defined (12).…”

Section: Scaledmentioning

confidence: 99%

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Development of a Multiplexed Tumor-Associated Autoantibody-Based Blood Test for the Detection of Non–Small Cell Lung Cancer

Farlow

Patel

Basu

et al. 2010

Clinical Cancer Research

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Purpose: Non-small cell lung cancer (NSCLC) has an overall 5-year survival of <15%; however, the 5-year survival for stage I disease is over 50%. Unfortunately, 75% of NSCLC is diagnosed at an advanced stage not amenable to surgery. A convenient serum assay capable of unambiguously identifying patients with NSCLC may provide an ideal diagnostic measure to complement computed tomography-based screening protocols.Experimental Design: Standard immunoproteomic method was used to assess differences in circulating autoantibodies among lung adenocarcinoma patients relative to cancer-free controls. Candidate autoantibodies identified by these discovery phase studies were translated into Luminex-based "direct-capture" immunobead assays along with 10 autoantigens with previously reported diagnostic value. These assays were then used to evaluate a second patient cohort composed of four discrete populations, including: 117 NSCLC (81 T 1-2 N 0 M 0 and 36 T 1-2 N 1-2 M 0 ), 30 chronic obstructive pulmonary disorder (COPD)/ asthma, 13 nonmalignant lung nodule, and 31 "normal" controls. Multivariate statistical methods were then used to identify the optimal combination of biomarkers for classifying patient disease status and develop a convenient algorithm for this purpose.Results: Our immunoproteomic-based biomarker discovery efforts yielded 16 autoantibodies differentially expressed in NSCLC versus control serum. Thirteen of the 25 analytes tested showed statistical significance (Mann-Whitney P < 0.05 and a receiver operator characteristic "area under the curve" over 0.65) when evaluated against a second patient cohort. Multivariate statistical analyses identified a six-biomarker panel with only a 7% misclassification rate.Conclusions: We developed a six-autoantibody algorithm for detecting cases of NSCLC among several high-risk populations. Population-based validation studies are now required to assign the true value of this tool for identifying early-stage NSCLC. Clin Cancer Res; 16(13); 3452-62. ©2010 AACR.Lung cancer remains the leading cause of cancer death nationwide, with ∼160,000 deaths predicted in the United States in 2009 (1). Non-small cell lung cancer (NSCLC) accounts for 80% of all lung cancers and has a poor overall 5-year survival rate of ∼15% (2-4). This low survival rate is largely attributed to the fact that >75% of patients present with local or distant metastasis at diagnosis, which are associated with a 21% and 3% 5-year survival, respectively (2,3,5). In contrast to these dismal figures, stage I disease is associated with a 50% to 67% 5-year survival but accounts for only 15% of patients (2). This suggests that if patients could be diagnosed at an earlier stage, when a complete surgical resection offers the greatest potential for a cure, the mortality associated with this disease could be reduced.To that end, considerable efforts have been undertaken to produce an effective screening method for early NSCLC. In the 1950s, trials of chest X-rays alone or in combination with sputum analysis were com...

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Section: Patient Populationsmentioning

confidence: 99%

Section: Scaledmentioning

confidence: 99%

Development of a Multiplexed Tumor-Associated Autoantibody-Based Blood Test for the Detection of Non–Small Cell Lung Cancer

Farlow

Patel

Basu

et al. 2010

Clinical Cancer Research

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“…Understanding of cancerogenesis requires a holistic approach including, analysis of epidemiological and clinical data, molecular testing of blood biomarkers and thorough analysis of tumor cells and immune cell infiltrate of the tumor. Data acquired over the last few decades has confirmed heterogeneity of cancer as a disease (2) which indicates there is no single perfect biomarker for lung cancer, but a panel of multiple parameters (3,4) could be a much more objective diagnostic and prognostic tool.…”

Section: Introductionmentioning

confidence: 99%

Role of CXC group chemokines in lung cancer development and progression

Špaks

2017

J. Thorac. Dis.

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Background: Clinical and translational research on lung cancer patients undergoing surgical treatment can provide valuable scientific data and unique opportunity to study tumor microenvironment. CXC chemokines, which are members of a big family of cytokines, are undoubtedly involved in tumor growth regulation and metastasizing pathways. For better understanding of CXC chemokine involvement in the process of carcinogenesis we have studied the cohort of early stage non-small cell lung cancer patients undergoing surgery with curative intent. Our aim was to assess CXC chemokine ligand (CXCL) levels in patient blood samples representing systemic circulation and tumor microenvironment; assess CXC chemokine receptor (CXCR) expression in tumor tissue; and measure tumor infiltrating immune cell subpopulations.Methods: A total of 54 patients with NSCLC had radical lung resection were enrolled in a single center prospective study and were followed-up annually for up to six years. During surgical procedure peripheral and tumor draining blood samples were taken. CXCL1, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8, CXCL9, CXCL10, CXCL11 and CXCL12 levels were determined by ELISA, and chemokine concentration gradient was calculated. Tumor infiltrating immune cells (T helper cells, T cytotoxic cells, macrophages, B cells, plasma cells) and expression of CXCR1, CXCR2, CXCR3 and CXCR4 in tumor tissue were assessed by immunohistochemistry. Results: Statistically significant decrease in chemokine concentration was found for CXCL4 (P=0.002) and CXCL5 (P=0.011), and statistically significant concentration increase was found for CXCL7 (P=0.001) in total cohort. We have found statistically significant CXC chemokine concentration change for majority of chemokines-CXCL1 (P=0.002), CXCL4 (P=0.001), CXCL5 (P=0.013), CXCL7 (P=0.036), CXCL8 (P=0.026), CXCL9 (P=0.034) and CXCL10 (P=0.032) in a group of patients who had good clinical result after surgery with no evidence of relapse, on the other hand patients with cancer recurrence including local and systemic cancer spread did not show any change of chemokine concentration in blood except for CXCL1 (P=0.041). We have also found that chemokine levels and gradients correlate with CXC receptor expression and number of tumor infiltrating immune cell subpopulations Conclusions: Assessment of tumor microcirculation is useful for evaluation of different types of circulating biomarkers and application of our method can be very wide, integrating thoracic surgeons into translational cancer research.

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“…The total 335 urine samples of Korean women were provided from ASAN Medical Center. The concentrations of urine protein biomarkers were measured using the multiplex immunoassay method with Luminex antibody microbeads: thereby, we used a multiplexed immunoassay kit consisting of cancer biomarkers specific to ovarian cancer [12]. Analyses were performed following the protocol of the manufacturer provided by Luminex Corp., and the samples were analyzed using the Bio-Plex Suspension Array System [13].…”

Section: Data Collectionmentioning

confidence: 99%

A Comparison of Optimal Biomarker Combinations for BenignCancer and Normal-Cancer Distinguishment in Ovarian Cancer Screening

Song

Kim

Chang

et al. 2014

IJBSBT

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Establishment of a Multi-Analyte Serum Biomarker Panel to Identify Lymph Node Metastases in Non-small Cell Lung Cancer

Abstract: This study establishes a serum biomarker panel with efficacy in discerning preoperative nodal status. With further validation, this blood test may be useful for assessing nodal status (including occult disease) in NSCLC patients facing tumor resection therapy.

Cited by 38 publications

References 45 publications

Development of a Multiplexed Tumor-Associated Autoantibody-Based Blood Test for the Detection of Non–Small Cell Lung Cancer

Development of a Multiplexed Tumor-Associated Autoantibody-Based Blood Test for the Detection of Non–Small Cell Lung Cancer

Role of CXC group chemokines in lung cancer development and progression

A Comparison of Optimal Biomarker Combinations for BenignCancer and Normal-Cancer Distinguishment in Ovarian Cancer Screening

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