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3.3 Antibody-based microarray     53




                  Analytical protein array that consists of antibodies or lectins to detect and/or quan-
                  tify a large number of proteins present in a biological sample. (2) Functional protein
                  arrays have used in studying the biochemistry properties of proteins, such as pro-
                  tein binding activities and enzyme-substrate relationships. (3) Reverse-phase protein
                  arrays, mostly have used to detect signaling pathways. Antibody-based microarray is
                  currently used in cancer diagnosis as it is noninvasive and has a high sensitivity for
                  detection of biomarkers and PTMs [25].



                  3.3  Antibody-based microarray
                  The microarray technique was first has introduced in the 1980s. The main aim of
                  this technique in cancer diagnosis was based on genome detection. This technique is
                  separated into four branches: microarray DNA, microarray protein, antibody-based
                  microarray, and microarray carbohydrate [22,24,25]. This technique is based on the
                  binding or hybridization of the sample with the template. Over time, the sensitivity
                  of the microarray has improved and its use has changed. Antibody-based microarray
                  is one of the microarray techniques that is used today for the detection of specific
                  biomarkers with high sensitivity. It has the benefit of rapid diagnostic speed and cost-
                  efficiency. In addition, microarray is a noninvasive procedure, and it is highlighted
                  in a study by Karen et al., which has demonstrated higher levels of serum protein in
                  patient plasma of cancer patients compared to control samples [27].
                     A drawback of protein biomarkers is a lack of specificity, with raised biomarkers
                  suggestive of more than one disease. Serum PSA is a protein that is elevated in some
                  benign prostate diseases as well as prostate cancer, or interleukin 6 (IL-6), is also a
                  protein biomarker which, if overexpressed in the serum of patients, could be known
                  as inflammation of the prostate, lung, multiple myeloma, and renal cell cancer Thus,
                  single cancer biomarkers are often not unique to a specific cancer. Antibody-based
                  microarray has the ability to concurrently detect multiple specific biomarkers, and
                  target-specific cancers using a panel of biomarkers [24,22].
                     In another study, further advantage of utilizing antibody microarray for early-
                  stage diagnosis has been reported. Pancreatic cancer is an aggressive disease with
                  poor prognosis, and most people die because of a delayed diagnosis. In the past, bio-
                  markers such as CA125 or CA19-9 could not be detected until advanced pancreatic
                  cancer stages; however, the high sensitivity technique which has acquired through
                  antibody-based microarray has caused such markers can be used before any crucial
                  progression occurs [28]. In an investigation of 148 patients with early-stage pan-
                  creatic cancer, chronic cancer, autoimmune pancreatitis (AIP), and control patients,
                  Wingren et al. have identified a panel of 25 protein targets such as IL-2, IL-11, IL-12,
                  TNF which distinguish pancreatic cancer from healthy controls. In pancreatic cancer,
                  these 25 biomarkers have shown a high sensitivity in cancer diagnosis (AUC 86%)
                  [28].
                     Moreover, microarray is also used in the diagnosis of prostate and breast cancer.
                  These findings are useful to aid the development of novel and multivariate diagnostics
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