Detection of tumor-specific autoantibodies in sera of patients with lung cancer

Nagashio, Ryo; Sato, Yuichi; Jiang, Shi‐Xu; Ryuge, Shinichiro; Kodera, Yasuhiro; Maeda, Tadakazu; Nakajima, Takashi

doi:10.1016/j.lungcan.2008.03.026

Cited by 46 publications

(43 citation statements)

References 39 publications

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“…This idea largely stems from the popular notion that although a cancer is still asymptomatic and in its early stages, autoantibodies produced in response to cancerspecific antigens may be detectable due to signal amplification from the humoral immune response. To date, numerous autoantibody targets have been evaluated for their value in early detection of lung cancer or for prognostication (13,16,19,22,27,(34)(35)(36)(37)(38)(39). Despite the promise these studies have shown in this direction, little has been done outside the initial discovery efforts to validate these findings and to translate these promising antibodies into a clinically usable test.…”

Section: Discussionmentioning

confidence: 99%

“…Of the analytes previously seen in the literature, IMPDH, Annexin II (16,34), ubiquilin (28), c-Myc (26), and α-enolase (23,35) showed the most promise (AUC > 0.63) for application in the early diagnosis of NSCLC. Interestingly, although p53 autoantibodies have been found to have numerous associations with regard to NSCLC, including the correlation with response to chemotherapy (20), with overall prognosis (21), and with serologic detection of disease (13,16,36,39), this marker was eliminated in the first iteration of the Random Forest multivariate statistical test. This is despite possessing excellent significance (ROC curve AUC = 0.628, P = 0.0023) in the univariate analysis.…”

Section: Discussionmentioning

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: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

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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“…Two-dimensional gel electrophoresis with agarose (agarose 2-DE) method was performed with minor modifications to make it suitable for mini-gel (Nagashio et al, 2008). In brief, LC2/ad-cis cells were solubilized in lysis buffer [7 M urea, 2 M thiourea, 2% 3-[(3-cholamidopropyl) dimethylammonio] propanesulfonic acid, 0.1 M dithiothreitol, 2.5% pH 3-10 Pharmalyte (GE Healthcare Bio-Sciences, Piscataway, NJ, USA), and 0.1 tablet/mL of complete mini EDTA-free protease inhibitors (Roche Diagnostics, Mannheim, Germany)] using an ultrasonic homogenizer (VP-050; TAITEC, Saitama, Japan), and centrifuged at 20,000 x g for 30 min at 4℃.…”

Section: Two-dimensional Gel Electrophoresis-immunoblottingmentioning

confidence: 99%

Serum Anti-Gal-3 Autoantibody is a Predictive Marker of the Efficacy of Platinum-Based Chemotherapy against Pulmonary Adenocarcinoma

Yanagita

Nagashio²,

Ryuge³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: Identification of predictive markers for the efficacy of platinum-based chemotherapy is necessary to improve the quality of the life of cancer patients. Materials and Methods: We detected proteins recognized by autoantibodies in pretreated sera from patients with lung adenocarcinoma (AC) evaluated as showing progressive disease (PD) or a partial response (PR) after cisplatin-based chemotherapy by proteomic analysis. Then, the levels of the candidate autoantibodies in the pretreated serum were validated by dot-blot analysis for 22 AC patients who received platinum-based chemotherapy, and the expression of identified proteins was immunohistochemically analyzed in 40 AC biopsy specimens. Results: An autoantibody against galectin-3 (Gal-3) was detected in pretreated sera from an AC patient with PD. Serum IgG levels of anti-Gal-3 autoantibody were significantly higher in patients evaluated with PD than in those with PR and stable disease (SD) (p = 0.0084). Furthermore, pretreated biopsy specimens taken from patients evaluated as showing PD following platinumbased chemotherapy showed a tendency to have a higher positive rate of Gal-3 than those with PR and SD (p = 0.0601). Conclusions: These results suggest that serum IgG levels of anti-Gal-3 autoantibody may be useful to predict the efficacy of platinum-based chemotherapy for patients with lung AC.

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“…formed according to our previous study (30). The first-dimensional agarose isoelectric focusing gel (75 mm in length and 2.5 mm in inner diameter) was made with single pharmalyte pH 3-10 (GE Healthcare Bio-Sciences Corp.).…”

Section: Two-dimensional Gel Electrophoresis 2-de Was Per-mentioning

confidence: 99%

Detection of tumor-associated antigens in culture supernatants using autoantibodiesin sera from patients with bladder cancer

Minami¹,

Nagashio²,

Ueda³

et al. 2014

Biomed. Res.

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Secreted proteins play essential roles in the process of tumorigenesis, and the analysis of tumorsecreted proteins has been suggested as a promising strategy for identifying cancer biomarkers. In this study, we performed proteomic analysis to identify proteins secreted from bladder cancer cell lines that are recognized by autoantibodies in sera from patients with bladder cancer. In addition, autoantibodies against the identified proteins were validated using a dot-blot array with sera from patients with bladder cancer and normal controls. As the results, we detected twenty-five and thirty-two immunoreactive spots in sera from patients with high-and low-grade bladder cancer, respectively. In addition, validation analysis revealed that serum IgG levels of anti-calreticulin and matrix metalloproteinase-2 (MMP2) autoantibodies were significantly higher in bladder cancer patients than in normal controls (both P < 0.05). Furthermore, the serum IgG level of anti-MMP2 autoantibody was significantly higher in patients with high-compared to low-grade bladder cancer (P < 0.05). On multivariate analysis, the serum IgG level of anti-MMP2 autoantibody was an independent predictor of cancer-specific survival (P < 0.05). Based on these findings, serum IgG levels of anti-calreticulin and MMP2 autoantibodies may be novel biomarker candidates for bladder cancer and its clinical outcome.Bladder cancer (BC) is the 7th most common cancer in men and the 17th most common in women in the world. The incidence of BC has been increasing in Japan, and it was about 20 and 5 per 100,000 Japanese males and females in 2002 (22). Approximately 75-85% of BC are diagnosed as non-muscle-invasive bladder cancer (NMIBC) at the first diagnosis, and around 70% of cases present as pTa, 20% as pT1, and 10% as carcinoma in situ lesions (23).NMIBC has a tendency to recur (50-70%) and may progress (10-20%) to a higher grade and/or muscleinvasive BC in time, which might lead to high cancer-specific mortality (46). The histological tumor grade is one of the clinical factors associated with outcomes of patients with NMIBC. High-grade NMIBC generally shows a more aggressive behavior than the low-grade form, and increases the risk of a poorer prognosis (3, 32). Due to the unfavorable prognosis associated with high-grade NMIBC, differential diagnosis between high-and low-grade NMIBC might be crucial for more appropriate follow-up and aggressive treatment. Cystoscopy and urine cytology are commonly used techniques for the diagnosis and surveillance of BC. Cystoscopy can identify most papillary and

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Detection of tumor-specific autoantibodies in sera of patients with lung cancer

Cited by 46 publications

References 39 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

Serum Anti-Gal-3 Autoantibody is a Predictive Marker of the Efficacy of Platinum-Based Chemotherapy against Pulmonary Adenocarcinoma

Detection of tumor-associated antigens in culture supernatants using autoantibodiesin sera from patients with bladder cancer

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