Tumors are formed by the unlimited proliferation of normal cells in living body and pose a serious threat to human health with high morbidity and mortality. Tumor-related biomarkers are a class of substances resulting from the tumor cell formation, release, or the body’s response to tumor cells, which are generated and increase during tumor development and proliferation. Tumor-related biomarkers may be divided into two categories: one is inside cancer cells (e.g., microRNA (miRNA), telomerase and transcription factor) and the other is on the cancer cell membranes (e.g., epithelial membrane antigen (EMA) and carcino-embryonic antigen (CEA)). Tumor-related biomarkers may reflect tumorigenesis, progression, and the responses to drug treatment. Consequently, the sensitive detection of tumor-related biomarkers is essential to early clinical diagnosis and therapy. Polymerase chain reaction (PCR) and immunohistochemistry technique have frequently been used to detect tumor-related biomarkers, but they are usually laborious and time-consuming. In recent years, sensitive detection of tumor-related biomarkers has become a hot area, with great progress having been made. A variety of methods including colorimetric, mass spectrometry, fluorescent, chemiluminescent, surface enhanced Raman scattering (SERS), electrochemical and single-molecule detection approaches have been developed for sensitive detection of tumor-related biomarker. Colorimetric assay has significant advantages of visualization, simple operation, high sensitivity, and no need for delicate instruments. The advantages of inductively coupled plasma mass spectrometric (ICPMS) include low detection limits, low matrix effects, large dynamic ranges and high spectral resolution for elements and isotopes. Fluorescent method allows for the homogeneous assay of biomarkers in solution with significant advantages of simplicity, low cost, high sensitivity, and safety without the requirement of radioisotopes. Chemiluminescent assay does not require an excitation laser, and the signal interferences from the background can be efficiently avoided. SERS is characterized by its capability to identify target analytes with an information-rich vibrational spectrum, and its narrow well-resolved peaks allow for simultaneous detection of multiple targets. Electrochemical method has the advantage of simplicity, low cost, and high sensitivity. In comparison with conventional ensemble measurements, single-molecule detection possess distinct advantages of ultrahigh sensitivity, good selectivity, rapid analysis time, and low sample-consumption. These methods have been successfully applied for sensitive detection of DNA, miRNA and proteins with high sensitivity and good selectivity. In addition, we give a new insight into future direction of tumor-related biomarker assay including: (1) the construction of novel fluorescent molecular probes which consist of nanoparticles (e.g., quantum dots) and biological recognition molecules (e.g., peptides, antibodies, and nucleic acids) for the detection of tumor-related biomarkers by taking advantage of the unique optical properties of nanoparticles such as tunable light emission, high brightness and multicolor excitation; (2) development of aptamer-based portable biosensors for the detection of tumor-related biomarkers by taking advantage of unique characteristics of aptamers such as convenient synthesis and controllable modification, high binding affinity and specificity, good stability, low toxicity, rapid tissue penetration, and low variability between different batches; (3) improvement of detection sensitivity through the introduction of amplification approaches such as isothermal nucleic acid amplification and hybridization chain reaction; and (4) the use of optical sensing and imaging techniques for simultaneous detection of multiple biomarkers by taking advantage of their unique properties such as high sensitivity, non-use of radioactive isotopes and multiplex detection capability.
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