Immunobiomarkers in Small Cell Lung Cancer: Potential Early Cancer Signals

Chapman, Caroline; Thorpe, Alison; Murray, Andrea; Parsy-Kowalska, Celine; Allen, Jonathan; Stafford, Kelly M.; Chauhan, Alok S.; Kite, Thomas A; Maddison, Paul; Robertson, J. F. R.

doi:10.1158/1078-0432.ccr-10-1363

Cited by 83 publications

(61 citation statements)

References 41 publications

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“…To counteract these mortality rates, research has focused on the development of diagnostic tools that enable the diagnosis of a cancer earlier before it progresses to an often incurable metastatic stage (5). Autoantibody levels in patient blood serum have been proposed as diagnostic biomarkers for early-stage diagnosis of cancers, as an increase in serum levels of certain autoantibodies has been shown to precede the development of disease symptoms (6, 7) and correlate with cancer incidence (8) for cancers of the breast (9), lung and small cell lung (10,11), colon (12), ovary (13), prostate (14), and head and neck cancer (15,16).…”

Section: Introductionmentioning

confidence: 99%

Serologic Autoantibodies as Diagnostic Cancer Biomarkers—A Review

Zaenker

Ziman

2013

Cancer Epidemiology, Biomarkers &Amp; Prevention

135

111

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Current diagnostic techniques used for the early detection of cancers are successful but subject to detection bias. A recent focus lies in the development of more accurate diagnostic tools. An increase in serologic autoantibody levels has been shown to precede the development of cancer disease symptoms. Therefore, autoantibody levels in patient blood serum have been proposed as diagnostic biomarkers for early-stage diagnosis of cancers. Their clinical application has, however, been hindered by low sensitivity, specificity, and low predictive value scores. These scores have been shown to improve when panels of multiple diagnostic autoantibody biomarkers are used. A five-marker biomarker panel has been shown to increase the sensitivity of prostate cancer diagnosis to 95% as compared with 12.2% for prostate-specific antigen alone. New potential biomarker panels were also discovered for lung, colon, and stomach cancer diagnosis with sensitivity of 76%, 65.4%, and 50.8%, respectively. Studies in breast and liver cancer, however, seem to favor single markers, namely a-2-HS-glycoprotein and des-g-carboxyprothrombin with sensitivities of 79% and 89% for the early detection of the cancers. The aim of this review is to discuss the relevance of autoantibodies in cancer diagnosis and to outline the current methodologies used in the detection of autoantibodies. The review concludes with a discussion of the autoantibodies currently used in the diagnosis of cancers of the prostate, breast, lung, colon, stomach, and liver. A discussion of the potential future use of autoantibodies as diagnostic cancer biomarkers is also included in this review. Cancer Epidemiol Biomarkers Prev; 22(12); 2161-81. Ó2013 AACR.

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Section: Introductionmentioning

confidence: 99%

Serologic Autoantibodies as Diagnostic Cancer Biomarkers—A Review

Zaenker

Ziman

2013

Cancer Epidemiology, Biomarkers &Amp; Prevention

135

111

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“…[10][11][12] SOX2 antibodies were detected by a semi-automated ELISA. 13 Neuronal surface antibodies were detected by scoring the serum IgG binding to live transfected human embryonic kidney 293 cells expressing the antigens, 14,15 with sera diluted 1:20 for LGI1 and NMDA receptor and 1:100 for CASPR2 and GABAb receptor. All positive results were repeated and read by a second observer and the sera tested for lack of binding to an alternative antigen.…”

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confidence: 99%

Paraneoplastic neurologic disorders in small cell lung carcinoma

et al. 2015

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Objective: To determine the frequency and range of paraneoplastic neurologic disorders (PNDs) and neuronal antibodies in small cell lung carcinoma (SCLC).Methods: Two hundred sixty-four consecutive patients with biopsy-proven SCLC were recruited at the time of tumor diagnosis. All patients underwent full neurologic examination. Serum samples were taken prior to chemotherapy and analyzed for 15 neuronal antibodies. Thirty-eight healthy controls were analyzed in parallel.Results: PNDs were quite prevalent (n 5 24, 9.4%), most frequently Lambert-Eaton myasthenic syndrome (3.8%), sensory neuronopathy (1.9%), and limbic encephalitis (1.5%). Eighty-seven percent of all patients with PNDs had antibodies to SOX2 (62.5%), HuD (41.7%), or P/Q VGCC (50%), irrespective of their syndrome. Other neuronal antibodies were found at lower frequencies (GABAb receptor [12.5%] and N-type VGCC [20.8%]) or very rarely (GAD65, amphiphysin, Ri, CRMP5, Ma2, Yo, VGKC complex, CASPR2, LGI1, and NMDA receptor [all ,5%]). Conclusions:The spectrum of PNDs is broader and the frequency is higher than previously appreciated, and selected antibody tests (SOX2, HuD, VGCC) can help determine the presence of an SCLC. Neurology ® 2015;85:235-239 GLOSSARY HC 5 healthy control; LE 5 limbic encephalitis; LEMS 5 Lambert-Eaton myasthenic syndrome; PCD 5 paraneoplastic cerebellar degeneration; PEM 5 paraneoplastic encephalomyelitis; PND 5 paraneoplastic neurologic disorder; SCLC 5 small cell lung carcinoma; SN 5 sensory neuronopathy.A paraneoplastic neurologic disorder (PND) results from the indirect effect of a tumor on the nervous system or muscle without local invasion or metastasis. PNDs are often associated with antibodies that bind to proteins shared between the tumor and the nervous system.

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“…Initially identified by serological analysis of expression cDNA libraries (SEREX; ref. 7), the presence of SOX2 autoantibodies (SOX2-Abs) in SCLC patients has been confirmed by several subsequent studies (6)(7)(8)(9)(10). The 22% to 33% frequency of SOX2-Abs has promising potential for clinical use.…”

Section: Introductionmentioning

confidence: 81%

“…To date, the immunogenicity of SOX2 had mainly been investigated in individuals with small cell lung carcinoma (SCLC; refs. [6][7][8][9][10]. Initially identified by serological analysis of expression cDNA libraries (SEREX; ref.…”

Section: Introductionmentioning

confidence: 99%

SOX2 Autoantibodies As Noninvasive Serum Biomarker for Breast Carcinoma

Sun¹,

Zhang²,

Wang³

et al. 2012

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: A clear association has been established between antibodies to the transcription factor sexdetermining region Y (SRY)-box 2 (SOX2) and small cell lung cancer. In light of the pathologic role of SOX2 and its aberrant expression in breast cancer, we measured serum SOX2 autoantibodies (SOX2-Abs) in breast cancer patients.Methods: The presence of SOX2-Abs was determined by an indirect enzyme-linked immunosorbent assay (ELISA) in sera from 282 patients with breast cancer, 78 patients with benign breast disease, and 194 healthy women.Results: SOX2-Abs were more prevalent in patients with breast cancer (18.4%) compared with healthy women (2.6%, P < 0.0001), and patients with benign breast disease (6.4%, P ¼ 0.011). The concentrations of circulating SOX2-Abs were found to discriminate between breast cancer patients and healthy controls (P < 0.001) and between breast cancer patients and those with benign breast disease (P < 0.001). In addition, measurement of SOX2-Abs was more effective than assays of serum tissue polypeptide-specific antigen, carcinoembryonic antigen, carbohydrate antigen (CA) 125, and CA 15-3 in distinguishing between malignant and benign breast disease. In breast cancer patients, the prevalence of SOX2-Abs was associated with a higher tumor grade (P ¼ 0.021) and positive nodal status (P ¼ 0.021).Conclusion: The presence of SOX2-Abs in breast cancer may be of clinical value. Impact: This study provides the first evidence for the presence of circulating SOX2-Abs in breast cancer and shows their potential clinical application. Cancer Epidemiol Biomarkers Prev; 21(11); 2043-7. Ó2012 AACR.

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Immunobiomarkers in Small Cell Lung Cancer: Potential Early Cancer Signals

Cited by 83 publications

References 41 publications

Serologic Autoantibodies as Diagnostic Cancer Biomarkers—A Review

Serologic Autoantibodies as Diagnostic Cancer Biomarkers—A Review

Paraneoplastic neurologic disorders in small cell lung carcinoma

SOX2 Autoantibodies As Noninvasive Serum Biomarker for Breast Carcinoma

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