Profiles of Plasma Serpins in Patients with Advanced Malignant Melanoma, Gastric Cancer and Breast Cancer

Wojtukiewicz, Marek Z.; Rucińska, Monika; Kłoczko, Janusz; Dib, A.; Galar, Marzenna

doi:10.1159/000022376

Cited by 9 publications

(9 citation statements)

References 25 publications

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“…While the expression of a number of serpins others than SERPINA1 has been reported in other tumour types, this is the first demonstration of the expression of SERPINA10 in a cancer. While the role of this gene in PETs remains unknown, specific profiles for plasma levels of different serpins have been reported (Wojtukiewicz et al 1998), and in our experiments a-1-antichymotrypsin (SERPINA3), another serpin commonly dysregulated in cancers (Bernacka et al 1998), was down-regulated. It would therefore be of interest to evaluate whether specific changes in circulating levels of SERPINA10 (and other SERPINs) occur in PET patients, and their possible relation with tumour stage and response to therapy.…”

Section: Discussionsupporting

confidence: 48%

Gene expression profiles of progressive pancreatic endocrine tumours and their liver metastases reveal potential novel markers and therapeutic targets

Capurso¹,

Lattimore²,

Crnogorac-Jurčević³

et al. 2006

Endocr Relat Cancer

101

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The intrinsic nature of tumour behaviour (stable vs progressive) and the presence of liver metastases are key factors in determining the outcome of patients with a pancreatic endocrine tumour (PET). Previous expression profile analyses of PETs were limited to non-homogeneous groups or to primary lesions only. The aim of this study was to investigate the gene expression profiles of a more uniform series of sporadic, non-functioning (NF) PETs with progressive disease and, for the first time, their liver metastases, on the Affymetrix human genome U133A and B GeneChip set. Thirteen NF PET samples (eight primaries and five liver metastases) from ten patients with progressive, metastatic disease, three cell lines (BON, QGP and CM) and four purified islet samples were analysed. The same samples were employed for confirmation of candidate gene expression by means of quantitative RT-PCR, while a further 37 PET and 15 carcinoid samples were analysed by immunohistochemistry. Analysis of genes differentially expressed between islets and primaries and metastases revealed 667 up-and 223 down-regulated genes, most of which have not previously been observed in PETs, and whose gene ontology molecular function has been detailed. Overexpression of bridging integrator 1 (BIN1) and protein Z dependent protease inhibitor (SERPINA10) which may represent useful biomarkers, and of lymphocyte specific protein tyrosine kinase (LCK) and bone marrow stromal cell antigen (BST2) which could be used as therapeutic targets, has been validated. When primary tumours were compared with metastatic lesions, no significantly differentially expressed genes were found, in accord with cluster analysis which revealed a striking similarity between primary and metastatic lesions, with the cell lines clustering separately. We have provided a comprehensive list of differentially expressed genes in a uniform set of aggressive NF PETs. A number of dysregulated genes deserve further in-depth study as potentially promising candidates for new diagnostic and treatment strategies. The analysis of liver metastases revealed a previously unknown high level of similarity with the primary lesions.

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Section: Discussionsupporting

confidence: 48%

Gene expression profiles of progressive pancreatic endocrine tumours and their liver metastases reveal potential novel markers and therapeutic targets

Capurso¹,

Lattimore²,

Crnogorac-Jurčević³

et al. 2006

Endocr Relat Cancer

101

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“…The relation between protease inhibitors, lung cancer and other cancers could not be stated with certainty. 20,21 In our study, a significant relation was not determined between the stage, histology and dissemination of tumor and serum levels of AAT and AMG in patients with lung cancer. A negative correlation between Alpha-1-antitrypsin and age is determined as well as a positive correlation between Alpha-2-macroglobulin and smoking (pack year).…”

Section: Discussioncontrasting

confidence: 55%

Are Serum Alpha-1-Antitrypsin and Alpha-2-Macroglobulin Levels Related with Tumor Histology or Stage of the Lung Cancer?.

Gassaloglu¹

2014

UHOD

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In certain types of cancer, increased serum protease inhibitor levels were identified and clues showing that, serum levels of protease inhibitor could be used in the assessment of prognosis and dissemination of tumor were obtained. We aimed to reveal whether serum alpha-1-antitrypsin (AAT) and alpha-2-macroglobulin (AMG) levels of patients with lung cancer are related with histological type, clinical stage, and advance of cancer. The patients enrolled in the study were the ones with a histopathologic diagnosis of primary lung cancer and they were not administered any treatment before. Levels of serum AAT and AMG were analyzed at the moment of diagnosis. A total of 47 patients were enrolled in the study -42 males and 5 females. The average age was 58.9. Tumor cell type was non-small cell lung carcinoma (NSCLC) in 36 and small cell lung carcinoma in 11 patients. There was a negative correlation between serum AAT level and age (p= 0.21 r=-0.339). No correlation was identified between serum AMG level and age (p= 0.138 r= 0.222). There was no significant relation between histological types of lung cancer and serums AAT and AMG (p= 0.807, p= 0.411 respectively). AAT and AMG levels were not different in limited and extensive small cell lung carcinoma (p= 0.201 and p= 0.465). AAT and AMG levels based on stages were not found to be different in NSCLC (p= 0.646 and p=0.650). AAT and AMG levels did not vary based on distant metastasis or local spread in NSCLC (p= 0.371 and p= 0.676). Serum alpha-1-antitrypsin and alpha-2-macroglobulin levels in patients with lung cancer do not vary based on histological types, stage of the disease, local, distant and lymphatic spread of the tumor.Keywords: Lung cancer, Alpha-1-antitrypsin, Alpha-2-macroglobulin, Histology, Stage, Metastasis ÖZET Akciğer Kanserinde Serum Alfa-1-Antitripsin ve Alfa-2-Makroglobulin Düzeyleri ile Tümor Histolojisi veya Yaygınlığı İlişkili mi?Bazı kanser tiplerinde artmış serum proteaz inhibitor düzeyleri saptanmış ve serum proteaz inhibitör düzeylerinin tümörün yaygınlığında, prognozun değerlendirilmesinde kullanılabileceğine dair ipuçları elde edilmiştir. Akciğer kanserli hastalarda serum alfa-1-antitripsin (AAT) ve alfa-2-makroglobulin (AMG) düzeyleri ile kanserin histolojik tipi, klinik evresi ve yaygınlığı arasında ilişki olup olmadığını ortaya koymayı amaçladık. Histopatolojik olarak primer akciğer kanseri tanısı konulan, herhangi bir tedavi uygulanmamış hastalar çalışmaya alındı. Teşhis anında serum AAT ve AMG düzeyleri incelendi. Çalışmaya 42 erkek ve 5 kadın, toplam 47 hasta alındı. Yaş ortalaması 58,9 yıl idi. Tümör hücre tipi 36 hastada küçük hücreli dışı akciğer karsinomu (KHDAK) ve 11 hastada küçük hücreli akciğer karsinomu idi. Serum AAT düzeyi ve yaş arasında negatif korelasyon var idi (p= 0.21 r=-0,339). Serum AMG düzeyi ve yaş arasında korelasyon saptanmadı (p= 0.138 r=0.222). Akciğer kanserinin histolojik tipleri ile serum AAT ve AMG arasında anlamlı ilişki saptanmadı (sırasıyla p= 0.807, p= 0,411). Küçük hücreli akciğer karsinomunda s...

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“…Whether these arise from blood or are true NAF constituents is irrelevant, however, in terms of the goal of the biomarker discovery project (18). Plasma antitrypsin was previously reported to be elevated in subjects with several types of cancer, with a significant increase in breast cancer (19). Serum levels of apolipoprotein A-I have been reported to be significantly higher in women with cancer recurrence than in women without cancer recurrence (20).…”

Section: Discussionmentioning

confidence: 99%

Detection of breast cancer biomarkers in nipple aspirate fluid by SELDI-TOF and their identification by combined liquid chromatography-tandem mass spectrometry

Gornbein²,

Shen³

et al. 2007

Int J Oncol

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Abstract. Screening mammography is the most effective tool available for breast cancer detection. While screening mammography saves lives, it has intrinsic problems that limit further improvement. We hypothesize that protein biomarkers in nipple aspirate fluid (NAF) may separate the cancer from the non-cancer state, and therefore can be used for breast cancer detection. In this study the proteins in NAF were analyzed by surface-enhanced laser desorption ionization coupled to time-of-flight mass spectrometry (SELDI-TOF) in the m/z 5,000-85,000 range. Two methods were used to normalize spectra. Then differentially expressed signals that separate cancer from non-cancer conditions were selected by two specifically developed statistical algorithms. Proteins of interest were identified by combined liquid chromatographytandem mass spectrometry. A set of 8 markers were identified which collectively gave 63% sensitivity, 89% specificity and 76% accuracy for distinguishing cancer from non-cancer. Further improvements in the specificity and sensitivity of this strategy could come from the development of methods for more precise quantification of the biomarkers of interest and also from focusing on the low abundant components that are not evident when unfractionated NAF is analyzed directly.

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Profiles of Plasma Serpins in Patients with Advanced Malignant Melanoma, Gastric Cancer and Breast Cancer

Cited by 9 publications

References 25 publications

Gene expression profiles of progressive pancreatic endocrine tumours and their liver metastases reveal potential novel markers and therapeutic targets

Gene expression profiles of progressive pancreatic endocrine tumours and their liver metastases reveal potential novel markers and therapeutic targets

Are Serum Alpha-1-Antitrypsin and Alpha-2-Macroglobulin Levels Related with Tumor Histology or Stage of the Lung Cancer?.

Detection of breast cancer biomarkers in nipple aspirate fluid by SELDI-TOF and their identification by combined liquid chromatography-tandem mass spectrometry

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