• Title/Summary/Keyword: tumor biomarker

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Tissue proteomics for cancer biomarker development - Laser microdissection and 2D-DIGE -

  • Kondo, Tadashi
    • BMB Reports
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    • v.41 no.9
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    • pp.626-634
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    • 2008
  • Novel cancer biomarkers are required to achieve early diagnosis and optimized therapy for individual patients. Cancer is a disease of the genome, and tumor tissues are a rich source of cancer biomarkers as they contain the functional translation of the genome, namely the proteome. Investigation of the tumor tissue proteome allows the identification of proteomic signatures corresponding to clinico-pathological parameters, and individual proteins in such signatures will be good biomarker candidates. Tumor tissues are also a rich source for plasma biomarkers, because proteins released from tumor tissues may be more cancer specific than those from non-tumor cells. Two-dimensional difference gel electrophoresis (2D-DIGE) with novel ultra high sensitive fluorescent dyes (CyDye DIGE Fluor satulation dye) enables the efficient protein expression profiling of laser-microdissected tissue samples. The combined use of laser microdissection allows accurate proteomic profiling of specific cells in tumor tissues. To develop clinical applications using the identified biomarkers, collaboration between research scientists, clinicians and diagnostic companies is essential, particularly in the early phases of the biomarker development projects. The proteomics modalities currently available have the potential to lead to the development of clinical applications, and channeling the wealth of produced information towards concrete and specific clinical purposes is urgent.

Statistical Method of Ranking Candidate Genes for the Biomarker

  • Kim, Byung-Soo;Kim, In-Young;Lee, Sun-Ho;Rha, Sun-Young
    • Communications for Statistical Applications and Methods
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    • v.14 no.1
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    • pp.169-182
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    • 2007
  • Receive operating characteristic (ROC) approach can be employed to rank candidate genes from a microarray experiment, in particular, for the biomarker development with the purpose of population screening of a cancer. In the cancer microarray experiment based on n patients the researcher often wants to compare the tumor tissue with the normal tissue within the same individual using a common reference RNA. Ideally, this experiment produces n pairs of microarray data. However, it is often the case that there are missing values either in the normal or tumor tissue data. Practically, we have $n_1$ pairs of complete observations, $n_2$ "normal only" and $n_3$ "tumor only" data for the microarray. We refer to this data set as a mixed data set. We develop a ROC approach on the mixed data set to rank candidate genes for the biomarker development for the colorectal cancer screening. It turns out that the correlation between two ranks in terms of ROC and t statistics based on the top 50 genes of ROC rank is less than 0.6. This result indicates that employing a right approach of ranking candidate genes for the biomarker development is important for the allocation of resources.

The targeting peptides for tumor receptor imaging

  • Yim, Min Su;Ryu, Eun Kyoung
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.2 no.2
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    • pp.63-68
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    • 2016
  • Peptides have been developed for in vivo imaging probes against to the specific biomarker in the biological process of living systems. Peptide based imaging probes have been applied to identify and detect their active sites using imaging modalities, such as PET, SPECT and MRI. Especially, tumor receptor imaging with the peptides has been widely used to specific tumor detection. This review discusses the targeting peptides that have been successfully characterized for tumor diagnosis by receptor imaging.

Proteomic Profiling of Serum from Stage I Lung Squamous Cell Carcinoma Patients

  • Li, Xin-Ju;Wu, Qi-Fei;He, Da-Lin;Fu, Jun-Ke;Jin, Xin
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2273-2276
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    • 2013
  • Objectives: This study employed proteomic profiling to identify specific tumor markers that might improve early diagnosis of lung squamous cell carcinoma. Methods: Serum samples were isolated from 30 patients with stage I lung squamous cell carcinoma and 30 age-and gender-matched healthy controls, and proteomic profiles were obtained by matrix-assisted laser desorption ionization time of flight mass spectrometry. Results: Three highly expressed potential tumor markers were identified in the sera of stage I lung squamous cell carcinoma patients, with molecular weights of 3261.69, 3192.07, and 2556.92 Da. One protein peak with molecular weight 3261.69 Da was chosen as the candidate biomarker and identified as a fibrinogen alpha chain through a search of the IPI, NCBI or SWISS-PROT protein databases. Conclusion: As a potential tumor biomarker, fibrinogen alpha chain may be applicable for the early diagnosis and prognosis of lung squamous cell carcinoma patients.

Mitochondrial DNA Levels in Blood and Tissue Samples from Breast Cancer Patients of Different Stages

  • Xia, Peng;Wang, Hui-Juan;Geng, Ting-Ting;Xun, Xiao-Jie;Zhou, Wen-Jing;Jin, Tian-Bo;Chen, Chao
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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    • pp.1339-1344
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    • 2014
  • Aims: Alterations in mitochondrial DNA (mtDNA) have been implicated in carcinogenesis and tumor progression. We here evaluated the diagnostic and prognostic potential of mtDNA as a biomarker for breast cancer. Methods: Using multiplex real-time polymerase chain reaction, nuclear DNA (nDNA) and mtDNA levels in serum, buffy coat, tumor, and tumor-adjacent tissue samples from 50 breast cancer patients were determined and assessed for associations with clinicopathological features. To evaluate mtDNA as a biomarker for distinguishing between the four sample types, we created receiver operating characteristic (ROC) curves. Results: The mtDNA levels in buffy coat were significantly lower than in other sample types. Relative to tumor-adjacent tissue, reduced levels of mtDNA were identified in buffy coat and tumor tissue but not in serum. According to ROC curve analysis, mtDNA levels could be used to distinguish between buffy coat and tumor-adjacent tissue samples with good sensitivity (77%) and specificity (83%). Moreover, mtDNA levels in serum and tumor tissue were positively associated with cancer TMN stage. Conclusions: The mtDNA levels in blood samples may represent a promising, non-invasive biomarker in breast cancer patients. Additional, large-scale validation studies are required to establish the potential use of mtDNA levels in the early diagnosis and monitoring of breast cancer.

Haptoglobin Levels in Turkish Patients with Bladder Cancer and its Association with Clinicopathological Features

  • Pirincci, Necip;Gecit, Ilhan;Gunes, Mustafa;Kemik, Ahu Sarbay;Yusel, Mehmet Bilgehan;Kaba, Mehmet;Ceylan, Kadir;Aslan, Mehmet
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6063-6066
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    • 2012
  • Although alteration in the haptoglobin phenotype has been reported in patients with bladder cancer, serum haptoglobin levels have not been evaluated. We hypothesized that serum haptoglobin can be used as a biomarker. The aim of this study was to evaluate the expression of haptoglobin in bladder cancer and to determine the relationship with clinicopathological features. A total of 68 serum specimens obtained before surgery were used to investigate haptoglobin expression using the sandwich ELISA technique. Serum haptoglobin levels were higher in the patients with bladder cancer compared to healthy controls (p<0.0001). Additionally, the levels of haptoglobin protein increased with increasing tumor grades (p<0.001) and were significantly higher in patients with metastatic disease and the presence of lymphovascular involvement, lymph node metastases and increasing tumor burden (p<0.0001). This study suggests that elevated haptoglobin levels are associated with a higher stage, grade, and extent of distant metastasis and larger tumor size. Haptoglobin may therefore provide a useful diagnostic and treatment biomarker for patients with bladder cancer.

SAMD13 as a Novel Prognostic Biomarker and its Correlation with Infiltrating Immune Cells in Hepatocellular Carcinoma

  • Hye-Ran Kim;Choong Won Seo;Jae-Ho Lee;Sang Jun Han;Jongwan Kim
    • Biomedical Science Letters
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    • v.28 no.4
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    • pp.260-275
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    • 2022
  • Sterile alpha motif (SAM) domains bind to various proteins, lipids, and RNAs. However, these domains have not yet been analyzed as prognostic biomarkers. In this study, SAM domain containing 13 (SAMD13), a member of the SAM domain, was evaluated to identify a novel prognostic biomarker in various human cancers, including hepatocellular carcinoma (HCC). Moreover, we identified a correlation between SAMD13 expression and immune cell infiltration in HCC. We performed bioinformatics analysis using online databases, such as Tumor Immune Estimation Resource, UALCAN, Kaplan-Meier plotter, LinkedOmics, and Gene Expression Profiling Interactive Analysis2. SAMD13 expression in HCC samples was significantly higher than that in normal liver tissue; additionally, SAMD13 was higher in primary tumors, various stages of cancer and grades of tumor, and status of nodal metastasis. Higher SAMD13 expression was also associated with poorer prognosis. SAMD13 expression positively correlated with CD8+ T cells, CD4+ T cells, B cells, neutrophils, macrophages, and dendritic cells. In the analysis of SAMD13 co-expression networks, positively related genes of SAMD13 were associated with a high hazard ratio in different types of cancer, including HCC. In biological function of SAMD13, SAMD13 mainly include spliceosome, ribosome biogenesis in eukaryote, ribosome, etc. These results suggest that SAMD13 may serve as a novel prognostic biomarker for HCC diagnosis and provide novel insights into tumor immunology in HCC.

Expression of IER3 in Primary Hepatocarcinoma: Correlation with Clinicopathological Parameters

  • Liu, Zhong;Wang, Xin-Mei;Jia, Tong-Fu;Zhai, Yi;Sun, Ling-Yan;Cheng, Yu-Ping;Zhang, Yue-Min;Liu, Shi-Hai;Liang, Jun
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.2
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    • pp.679-682
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    • 2015
  • Background: Studies indicate the immediate early response gene 3 (IER3) is involved in many biological processes. Recently, it was discovered that IER3 plays an important role in tumorigenesis and tumor progression. Thus it may be a valuable biomarker in tumor. This study was designed to investigate the expression status of IER3 in primary hepatocarcinoma (PHC) and correlation with clinicopathological parameters. Materials and Methods: Real-time PCR was performed to evaluate the expression levels of IER3 in 62 pathologically diagnosed human PHC specimens. Results: A statistically significant association was disclosed between the expression of IER3 and P53 mutant protein (short for P53), Ki-67, EGFR and the biggest diameter, differentiation grade of tumor. Conclusions: This work is the first to shed light on the potential clinical usefulness of IER3, as an efficient tumor biomarker in PHC.

Tumor-Suppression Mechanisms of Protein Tyrosine Phosphatase O and Clinical Applications

  • Kang, Man-Man;Shan, Shun-Lin;Wen, Xu-Yang;Shan, Hu-Sheng;Wang, Zheng-Jun
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6215-6223
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    • 2015
  • Tyrosine phosphorylation plays an important role in regulating human physiological and pathological processes. Functional stabilization of tyrosine phosphorylation largely contributes to the balanced, coordinated regulation of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Research has revealed PTPs play an important suppressive role in carcinogenesis and progression by reversing oncoprotein functions. Receptor-type protein tyrosine phosphatase O (PTPRO) as one member of the PTPs family has also been identified to have some roles in tumor development. Some reports have shown PTPRO over-expression in tumors can not only inhibit the frequency of tumor cell division and induce tumor cell death, but also suppress migration. However, the tumor-suppression mechanisms are very complex and understanding is incomplete, which in some degree blocks the further development of PTPRO. Hence, in order to resolve this problem, we here have summarized research findings to draw meaningful conclusions. We found tumor-suppression mechanisms of PTPRO to be diverse, such as controlling G0/G1 of the tumor cell proliferation cycle, inhibiting substrate phosphorylation, down-regulating transcription activators and other activities. In clinical anticancer efforts, expression level of PTPRO in tumors can not only serve as a biomarker to monitor the prognosis of patients, but act as an epigenetic biomarker for noninvasive diagnosis. In addition, the re-activation of PTPRO in tumor tissues, not only can induce tumor volume reduction, but also enhance the susceptibility to chemotherapy drugs. So, we can propose that these research findings of PTPRO will not only support new study ideas and directions for other tumor-suppressors, importantly, but also supply a theoretical basis for researching new molecular targeting agents in the future.

The Overview of the Importances of Tumor Suppressor p53 for Investigating Molecular Toxicological Mechanisms of Various Environmental Mutagens (다양한 환경변이원의 분자독성학적 메커니즘 연구에 있어서 항종양 인자 p53의 중요성 고찰)

  • Jung Hwa Jin;Ryu Jae-Chun;Seo Young Rok
    • Environmental Analysis Health and Toxicology
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    • v.19 no.3
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    • pp.321-326
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    • 2004
  • The study of p53 tumor suppressor protein is one of most important subjects in an environmental toxicology as well as in cancer biology. Generally, p53 has been known to involve the cell cycle regulation and apoptosis by the activation of its target genes such as p21 and bax in a number of cellular stress responses. In addition, associations of p53 with cellular proteins presumably reflect the involvement of p53 in critical cellular processes such as DNA repair. The complex formation of p53 and exogenous proteins such as viral or cellular proteins has been shown in many cases to play important roles in carcinogenic processes against environmental mutagen. Recently, the disruption of p53 protein by oxidative stress has been also reported to have relevance to carcinogenesis. These findings suggested that the maintaining of stability and functional activity of p53 protein was also important aspect to play as a tumor suppressor protein. Therefore, the detection of functional status of p53 proteins might be an effective biomarker for the cancer and human diseases under the environmental toxicologic carcinogen.