• 제목/요약/키워드: Cancer biomarker

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Pros and cons of using aberrant glycosylation as companion biomarkers for therapeutics in cancer

  • Kang, Jeong-Gu;Ko, Jeong-Heon;Kim, Yong-Sam
    • BMB Reports
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    • 제44권12호
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    • pp.765-771
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    • 2011
  • Cancer treatment has been stratified by companion biomarker tests that serve to provide information on the genetic status of cancer patients and to identify patients who can be expected to respond to a given treatment. This stratification guarantees better efficiency and safety during treatment. Cancer patients, however, marginally benefit from the current companion biomarker-aided treatment regimens, presumably because companion biomarker tests are dependent solely on the mutation status of several genes status quo. In the true sense of the term, "personalized medicine", cancer patients are deemed to be identified individually by their molecular signatures, which are not necessarily confined to genetic mutations. Glycosylation is tremendously dynamic and shows alterations in cancer. Evidence is accumulating that aberrant glycosylation contributes to the development and progression of cancer, holding the promise for use of glycosylation status as a companion biomarker in cancer treatment. There are, however, several challenges derived from the lack of a reliable detection system for aberrant glycosylation, and a limited library of aberrant glycosylation. The challenges should be addressed if glycosylation status is to be used as a companion biomarker in cancer treatment and contribute to the fulfillment of personalized medicine.

Calnexin as a dual-role biomarker: antibody-based diagnosis and therapeutic targeting in lung cancer

  • Soyeon Lim;Youngeun Ha;Boram Lee;Junho Shin;Taiyoun Rhim
    • BMB Reports
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    • 제57권3호
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    • pp.155-160
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    • 2024
  • Lung cancer carries one of the highest mortality rates among all cancers. It is often diagnosed at more advanced stages with limited treatment options compared to other malignancies. This study focuses on calnexin as a potential biomarker for diagnosis and treatment of lung cancer. Calnexin, a molecular chaperone integral to N-linked glycoprotein synthesis, has shown some associations with cancer. However, targeted therapeutic or diagnostic methods using calnexin have been proposed. Through 1D-LCMSMS, we identified calnexin as a biomarker for lung cancer and substantiated its expression in human lung cancer cell membranes using Western blotting, flow cytometry, and immunocytochemistry. Anti-calnexin antibodies exhibited complement-dependent cytotoxicity to lung cancer cell lines, resulting in a notable reduction in tumor growth in a subcutaneous xenograft model. Additionally, we verified the feasibility of labeling tumors through in vivo imaging using antibodies against calnexin. Furthermore, exosomal detection of calnexin suggested the potential utility of liquid biopsy for diagnostic purposes. In conclusion, this study establishes calnexin as a promising target for antibody-based lung cancer diagnosis and therapy, unlocking novel avenues for early detection and treatment.

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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    • 제14권1호
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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.

Biomarker-directed Targeted Therapy in Colorectal Cancer

  • John M. Carethers
    • Journal of Digestive Cancer Research
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    • 제3권1호
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    • pp.5-10
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    • 2015
  • With advances in the understanding of the biology and genetics of colorectal cancer (CRC), diagnostic biomarkers that may predict the existence or future presence of cancer or a hereditary condition, and prognostic and treatment biomarkers that may direct the approach to therapy have been developed. Biomarkers can be ascertained and assayed from any tissue that may demonstrate the diagnostic or prognostic value, including from blood cells, epithelial cells via buccal swab, fresh or archival cancer tissue, as well as from cells shed into fecal material. For CRC, current examples of biomarkers for screening and surveillance include germline testing for suspected hereditary CRC syndromes, and stool DNA tests for screening average at-risk patients. Molecular biomarkers for CRC that may alter patient care and treatment include the presence or absence of microsatellite instability, the presence or absence of mutant KRAS, BRAF or PIK3CA, and the level of expression of 15-PGDH in the colorectal mucosa. Molecularly targeted therapies and some general therapeutic approaches rely on biomarker information. Additional novel biomarkers are on the horizon that will undoubtedly further the approach to precision or individualized medicine.

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Biological Functions and Identification of Novel Biomarker Expressed on the Surface of Breast Cancer-Derived Cancer Stem Cells via Proteomic Analysis

  • Koh, Eun-Young;You, Ji-Eun;Jung, Se-Hwa;Kim, Pyung-Hwan
    • Molecules and Cells
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    • 제43권4호
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    • pp.384-396
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    • 2020
  • Breast cancer is one of the most common life-threatening malignancies and the top cause of cancer deaths in women. Although many conventional therapies exist for its treatment, breast cancer still has many handicaps to overcome. Cancer stem cells (CSCs) are a well-known cause of tumor recurrences due to the ability of CSCs for self-renewal and differentiation into cell subpopulations, similar to stem cells. To fully treat breast cancer, a strategy for the treatment of both cancer cells and CSCs is required. However, current strategies for the eradication of CSCs are non-specific and have low efficacy. Therefore, surface biomarkers to selectively treat CSCs need to be developed. Here, 34 out of 641 surface biomarkers on CSCs were identified by proteomic analysis between the human breast adenocarcinoma cell line MCF-7 and MCF-7-derived CSCs. Among them, carcinoembryonic antigen-related cell adhesion molecules 6 (CEACAM6 or CD66c), a member of the CEA family, was selected as a novel biomarker on the CSC surface. This biomarker was then experimentally validated and evaluated for use as a CSC-specific marker. Its biological effects were assessed by treating breast cancer stem cells (BCSCs) with short hairpin (sh)-RNA under oxidative cellular conditions. This study is the first to evaluate the biological function of CD66c as a novel biomarker on the surface of CSCs. This marker is available as a moiety for use in the development of targeted therapeutic agents against CSCs.

Current and New Molecularly Targeted Agents for Metastatic Gastric Cancer

  • Sung Chul Park
    • Journal of Digestive Cancer Research
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    • 제3권1호
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    • pp.11-16
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    • 2015
  • The discovery of HER2, a biomarker in advanced gastric cancer, and successful clinical trial using trastuzumab that targets this biomarker signaled a revolutionary turning point in treatment of metastatic gastric cancer. Many studies about targeted agents for gastric cancer have been attempted. Among them, ramicirumab, a monoclonal antibody that targets vascular endothelial growth factor receptor-2 (VEGFR-2), and apatinib, a tyrosine kinase inhibitor (TKI) that targets VEGFR2, have shown to improve the survival rates in advanced gastric cancer patients, for whom previous therapies had failed; hence, they are expected to be accepted as one of the standard therapies for advanced gastric cancer.

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Saliva Supernatant miR-21: a Novel Potential Biomarker for Esophageal Cancer Detection

  • Xie, Zi-Jun;Chen, Gang;Zhang, Xu-Chao;Li, Dong-Feng;Huang, Jian;Li, Zi-Jun
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권12호
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    • pp.6145-6149
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    • 2012
  • Objective: To identify whether saliva supernatant miR-21 can serve as a novel potential biomarker in patients with esophageal cancer (EC). Methods: 32 patients with EC and 16 healthy controls were recruited in this study. Total RNA was extracted from saliva supernatant samples for measurement of miR-21 levels using RT-qPCR and relationships between miR-21 levels and clinical characteristics of EC patients were analyzed. Results: miR-21 was significantly higher in the EC than control groups. The sensitivity and specificity were 84.4% and 62.5% respectively. Supernatant miR-21 levels showed no significant correlation with cancer stage, differentiation and nodal metastasis. Conclusions: Saliva supernatant miR-21 may be a novel biomarker for EC.

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

  • Kondo, Tadashi
    • BMB Reports
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    • 제41권9호
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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.

전립선암 진단을 위한 바이오마커 패널 (A Panel of Serum Biomarkers for Diagnosis of Prostate Cancer)

  • 조정기;김영희
    • 대한의용생체공학회:의공학회지
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    • 제38권5호
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    • pp.271-276
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    • 2017
  • Cancer biomarkers are using in the diagnosis, staging, prognosis and prediction of disease progression. But, there are not sufficiently profiled and validated in early detection and risk classification of prostate cancer. In this study, we have devoted to finding a panel of serum biomarkers that are able to detect the diagnosis of prostate cancer. The serum samples were consisted of 111 prostate cancer and 343 control samples and examined. Eleven biomarkers were constructed in this study, and then nine biomarkers were relevant to candidate biomarkers by using t test. Finally, four biomarkers, PSA, ApoA2, CYFRA21.1 and TTR, were selected as the prostate cancer biomarker panel, logistic regression was used to identify algorithms for diagnostic biomarker combinations(AUC = 0.9697). A panel of combination biomarkers is less invasive and could supplement clinical diagnostic accuracy.

Diagnostic Value of Fecal Calprotectin as a Screening Biomarker for Gastrointestinal Malignancies

  • Khoshbaten, Manouchehr;Pishahang, Parinaz;Nouri, Mohammad;Lashkari, Alireza;Alizadeh, Mahasti;Rostami-Nejad, Mohammad
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권4호
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    • pp.1667-1670
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    • 2014
  • Background: Calprotectin in feces seems to be a more sensitive marker for gastrointestinal (GI) cancers than fecal occult blood, but its specificity may be too low for screening average risk populations. This study aims at evaluating the diagnostic value of fecal calprotectin as a screening biomarker for GI malignancies. Materials and Methods: In a case-control study, 100 patients with GI malignancies (50 patients with colorectal cancer and 50 patients with gastric cancer) and 50 controls were recruited in Tabriz Imam Reza and Sina hospitals during a 24-month period. One to two weeks after the last endoscopy/colonoscopy, fecal specimens were collected by the patients and examined by ELISA method for quantitative measurement of calprotectin content. The results were compared between the three groups. Results: The mean fecal calprotectin level was $109.1{\pm}105.3$ (2.3-454.3, median:74), $241.1{\pm}205.2$ (3.4-610.0, median:19.3) and $45.9{\pm}55.1{\mu}g/g$ (1.3-257.1, median:19.3) in gastric cancer, colorectal cancer and control group, respectively, the differences being significant (p<0.001) and remaining after adjustment for age. The optimal cut-off point for fecal calprotectin was ${\geq}75.8{\mu}g/g$ for distinguishing colorectal cancer from normal cases (sensitivity and specificity of 80% and 84%, respectively). This value was ${\geq}41.9{\mu}g/g$ for distinguishing gastric cancer from normal cases (sensitivity and specificity of 62%). Conclusions: Our results revealed that fecal calprotectin might be a useful and non-invasive biomarker for distinguishing colorectal cancer from non-malignant GI conditions. However, due to low sensitivity and specificity, this biomarker may not help physicians distinguishing gastric cancer cases from healthy subjects.