22
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Current and Prospective Protein Biomarkers of Lung Cancer

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Lung cancer is a malignant lung tumor with various histological variants that arise from different cell types, such as bronchial epithelium, bronchioles, alveoli, or bronchial mucous glands. The clinical course and treatment efficacy of lung cancer depends on the histological variant of the tumor. Therefore, accurate identification of the histological type of cancer and respective protein biomarkers is crucial for adequate therapy. Due to the great diversity in the molecular-biological features of lung cancer histological types, detection is impossible without knowledge of the nature and origin of malignant cells, which release certain protein biomarkers into the bloodstream. To date, different panels of biomarkers are used for screening. Unfortunately, a uniform serum biomarker composition capable of distinguishing lung cancer types is yet to be discovered. As such, histological analyses of tumor biopsies and immunohistochemistry are the most frequently used methods for establishing correct diagnoses. Here, we discuss the recent advances in conventional and prospective aptamer based strategies for biomarker discovery. Aptamers like artificial antibodies can serve as molecular recognition elements for isolation detection and search of novel tumor-associated markers. Here we will describe how these small synthetic single stranded oligonucleotides can be used for lung cancer biomarker discovery and utilized for accurate diagnosis and targeted therapy. Furthermore, we describe the most frequently used in-clinic and novel lung cancer biomarkers, which suggest to have the ability of differentiating between histological types of lung cancer and defining metastasis rate.

          Related collections

          Most cited references124

          • Record: found
          • Abstract: found
          • Article: not found

          Exosomal microRNA: a diagnostic marker for lung cancer.

          To date, there is no screening test for lung cancer shown to affect overall mortality. MicroRNAs (miRNAs) are a class of small noncoding RNA genes found to be abnormally expressed in several types of cancer, suggesting a role in the pathogenesis of human cancer. We evaluated the circulating levels of tumor exosomes, exosomal small RNA, and specific exosomal miRNAs in patients with and without lung adenocarcinoma, correlating the levels with the American Joint Committee on Cancer (AJCC) disease stage to validate it as an acceptable marker for diagnosis and prognosis in patients with adenocarcinoma of the lung. To date, 27 patients with lung adenocarcinoma AJCC stages I-IV and 9 controls, all aged 21-80 years, were enrolled in the study. Small RNA was detected in the circulating exosomes. The mean exosome concentration was 2.85 mg/mL (95% CI, 1.94-3.76) for the lung adenocarcinoma group versus 0.77 mg/mL (95% CI, 0.68-0.86) for the control group (P < .001). The mean miRNA concentration was 158.6 ng/mL (95% CI, 145.7-171.5) for the lung adenocarcinoma group versus 68.1 ng/mL (95% CI, 57.2-78.9) for the control group (P < .001). Comparisons between peripheral circulation miRNA-derived exosomes and miRNA-derived tumors indicated that the miRNA signatures were not significantly different. The significant difference in total exosome and miRNA levels between lung cancer patients and controls, and the similarity between the circulating exosomal miRNA and the tumor-derived miRNA patterns, suggest that circulating exosomal miRNA might be useful as a screening test for lung adenocarcinoma. No correlation between the exosomal miRNA levels and the stage of disease can be made at this point.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Malignant effusions and immunogenic tumour-derived exosomes.

            Exosomes derived from tumours are small vesicles released in vitro by tumour cell lines in culture supernatants. To assess the role of these exosomes in vivo, we examined malignant effusions for their presence. We also investigated whether these exosomes could induce production of tumour-specific T cells when pulsed with dendritic cells. We isolated exosomes by ultracentrifugation on sucrose and D(2)O gradients of 11 malignant effusions. We characterised exosomes with Western blot analyses, immunoelectron microscopy, and in-vitro stimulations of autologous T lymphocytes. Malignant effusions accumulate high numbers of membrane vesicles that have a mean diameter of 80 nm (SD 30). These vesicles have antigen-presenting molecules (MHC class-I heat-shock proteins), tetraspanins (CD81), and tumour antigens (Her2/Neu, Mart1, TRP, gp100). These criteria, including their morphological characteristics, indicate the similarities between these vesicles and exosomes. Exosomes from patients with melanoma deliver Mart1 tumour antigens to dendritic cells derived from monocytes (MD-DCs) for cross presentation to clones of cytotoxic T lymphocytes specific to Mart1. In seven of nine patients with cancer, lymphocytes specific to the tumour could be efficiently expanded from peripheral blood cells by pulsing autologous MD-DCs with autologous ascitis exosomes. In one patient tested, we successfully expanded a restricted T-cell repertoire, which could not be recovered carcinomatosis nodules. Exosomes derived from tumours accumulate in ascites from patients with cancer. Ascitis exosomes are a natural and new source of tumour-rejection antigens, opening up new avenues for immunisation against cancers.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials.

              Promising results from new approaches such as radiosurgery or stereotactic surgery of brain metastases have recently been reported. Are these results due to the therapy alone or can the results be attributed in part to patient selection? An analysis of tumor/patient characteristics and treatment variables in previous Radiation Therapy Oncology Group (RTOG) brain metastases studies was considered necessary to fully evaluate the benefit of these new interventions. The database included 1200 patients from three consecutive RTOG trials conducted between 1979 and 1993, which tested several different dose fractionation schemes and radiation sensitizers. Using recursive partitioning analysis (RPA), a statistical methodology which creates a regression tree according to prognostic significance, eighteen pretreatment characteristics and three treatment-related variables were analyzed. According to the RPA tree the best survival (median: 7.1 months) was observed in patients or = 70, < 65 years of age with controlled primary and no extracranial metastases; Class 3: KPS < 70; Class 2- all others. Using these classes or stages, new treatment techniques can be tested on homogeneous patient groups.
                Bookmark

                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                13 November 2017
                November 2017
                : 9
                : 11
                : 155
                Affiliations
                [1 ]Laboratory for Biomolecular and Medical Technologies, Krasnoyarsk State Medical University named after prof. V.F. Voino-Yaseneckii, 1 P. Zheleznyaka, Krasnoyarsk 660022, Russia; tzamay@ 123456yandex.ru (T.N.Z.); galina.zamay@ 123456gmail.com (G.S.Z.); olga.kolovskaya@ 123456gmail.com (O.S.K.)
                [2 ]Departments of Physiology, Krasnoyarsk State Medical University named after prof. V.F. Voino-Yaseneckii, 1 P. Zheleznyaka, Krasnoyarsk 660022, Russia
                [3 ]Federal Research Center, Siberian Branch of the Russian Academy of Science, 50/24 Akademgorodok, Krasnoyarsk 660036, Russia
                [4 ]Departments of Oncology and Radiation Theraphy, Krasnoyarsk State Medical University named after prof. V.F. Voino-Yaseneckii, 1 P. Zheleznyaka, Krasnoyarsk 660022, Russia; zukov_rus@ 123456mail.ru
                [5 ]Krasnoyarsk Regional Clinical Cancer Center named after A.I. Kryzhanovsky, Krasnoyarsk 660133, Russia
                [6 ]Departments of Polyclinic therapy and Family Medicine, Krasnoyarsk State Medical University named after prof. V.F. Voino-Yaseneckii, 1 P. Zheleznyaka, Krasnoyarsk 660022, Russia; stk99@ 123456yandex.ru
                [7 ]Independent Researcher Vancouver, 207-2145 York Avenue, Vancouver, BC V6K 1C4, Canada; ana.gargaun@ 123456gmail.com
                [8 ]Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON K1N6N5, Canada; maxim.berezovski@ 123456uottawa.ca
                [9 ]Departments of Pharmacology, Krasnoyarsk State Medical University named after prof. V.F. Voino-Yaseneckii, 1 P. Zheleznyaka, Krasnoyarsk 660022, Russia
                Author notes
                [* ]Correspondence: azamay@ 123456krasgmu.ru ; Tel.: +7-903-923-8402
                Author information
                https://orcid.org/0000-0003-1054-4629
                Article
                cancers-09-00155
                10.3390/cancers9110155
                5704173
                29137182
                b6a1baae-4581-4f60-8e9c-c34f095cca7d
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 12 October 2017
                : 06 November 2017
                Categories
                Review

                lung cancer,biomarker,histological type,aptamers,diagnostics,targeted therapy

                Comments

                Comment on this article