Kharbanda Sulabh; International Journal of Advance Research, Ideas and Innovations in Technology

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Biomarkers- Emerging applications of biomarkers in healthcare
Dr. Sulabh Kharbanda
sulabhchandra2000@gmail.com
Mangalmay Institute of Engineering and Technology, Greater Noida, Uttar Pradesh

ABSTRACT study of peaks by mass spectroscopy, two-dimensional gel

electrophoresis and isoelectric focusing [4].
Biomarkers are a small protein or peptide molecules which
are part of cell receptors, cell signalling molecules involved in 1.1 Traditional applications of biomarkers
cell-cell signalling or cell protein kinase activation and Applications of biomarkers involve the study of these
transfer of the signal to the nucleus with the regulation of molecules in various cancer diseases like hepatocellular cancer,
gene transcription. Biomarkers have functional significance prostate cancer, lung, liver, stomach, oral, non-small lung
in the recognition of different stages of cancer, therapy for cancer, head and neck cancer, ovarian cancer and cervical
cancer, and the identification of different types of cancer of cancer. Various techniques like peptide mass fingerprinting,
different organs according to the biomarker present. It is also surface enhanced laser desorption studies, immunoaffinity
used for the diagnosis and analysis of mutations in various metal chelations studies with nickel metal and biomarker
proteins and identification of single nucleotide polymorphism protein molecules in columns, differential gel electrophoresis,
in genes, screening of diseases, and classification of diseases cation exchange and anion exchange chromatography are
in humans and development of target inhibitor molecules essential for cancer studies. The other techniques are stable
against the biomarkers. Various other studies have indicated isotope labelling of amino acids in cell culture, multi-
the presence of autoantibodies against proteins of the cells dimensional techniques, matrix-assisted laser desorption
which act as biomarkers in different grades of cancer and studies, mass spectroscopy and capillary electrophoresis along
autoimmune response. with the study of post-translational modifications of amino
acids in biomarker proteins are essential for the studies of
Keywords— Biomarkers, Ovarian cancer, Breast cancer, proteins.[2,4] (Figure 1). Further microbial proteomics study is
Prostate cancer, Pharmacological markers, Drug screening performed to study the pathogenicity clusters in bacteria,
1. INTRODUCTION TO APPLICATIONS OF infection-causing proteins in bacteria, genome analysis of
BIOMARKERS bacteria and protein toxins
Potential applications of biomarkers include the analysis and
screening of protein molecules, characterisation, post-
translational modifications like glycosylations, and prediction
of the structure of molecules. Other applications include the
analysis and study of phosphorylation patterns and protein-
protein interactions of protein biomarkers during activation of
cell signalling mechanisms inside the cell. Biomarkers are used
for the study of pharmacological inhibitors, the study of
mutations in biomarker proteins due to somatic and germline
mutations in genes during transfer of characters and traits from
one generation to another in humans. The other functions are
analysis of subunit of protein biomarkers and their activation
mechanism in cells during cancer, therapy models for
identification and recognition of cancer of different organs,
study of storage of biomarkers in various organelles as well the
study of sorting and targeting of folded and misfolded protein
biomarkers in endoplasmic reticulum, golgi apparatus along
with their degradation by chaperone pathway [2].
Transcriptome-based genomic and proteomic techniques are Fig. 1: The applications include the techniques used in the
used for the analysis and characterisation of biomarkers identification and screening of biological biomarkers source-
involving digestion of peptide with enzymes like trypsin and Mining the plasma proteome for cancer biomarkers [9]

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 Kharbanda Sulabh; International Journal of Advance Research, Ideas and Innovations in Technology
causing disease in humans, antimicrobial proteins involved in Further pharmacological screening is performed for the
killing other different microorganism population of bacteria in efficiency, affinity of binding, inhibition of biomarker protein
microbial consortium [4].In addition to this, miRNA profiling in cells and drug-biomarker protein interactions in cell lines
has been performed for the study of cancer biomarkers with the (Figure 2). The drug-mediated targeting the cancerous organ is
study of the regions of binding of protein biomarker miRNA performed with the help of liposomes, virus-mediated therapy,
along with target therapy for the analysis of inhibition of nanoparticles, micelles, dendrimers, photodynamic therapy,
miRNA expressions and its down-regulation and up-regulation fluorescent labelling of biomarker protein molecules and
in various grades of cancer [5]. visualisation by biomedical imaging [11] along with
pharmacological docking, affinity studies, inhibition studies of
2. EMERGING ROLES OF BIOMARKERS drug and protein biomarkers like drug-EGFR (HER-2)
The protein biomarkers are analysed in various cancerous mediated therapy [12] and drug interaction with mTOR
organs for example glycoprotein CA-125, VEGF(vascular signalling pathway proteins with rapamycin [13]. The anti-
endothelial growth factor), transferrin, apolipoprotein A1 level EGFR receptor protein which is a biomarker binds to the
and transthyretin levels, carcinogenic embryogenic antigen inhibitor drug molecules and prevents the phosphorylation of
(CEA) in ovarian cancer, prostate-specific antigen, prostate the tyrosine amino acid on the EGFR receptor thus preventing
acid phosphatases, and serum acid phosphatases in prostate the activation of cell signalling [12]. Major protein biomarkers
cancer. Hepatocyte growth factor, survivin, alpha-fetoprotein, used in drug metabolism include cytochrome P450 enzymes in
neuroserpin levels in hepatocellular carcinoma, atrial natriuretic the liver [15].
factor in heart diseases, alpha-synuclein, PINK proteins
(PARK), glial fibrillary acidic protein, galectin in Parkinson Further pharmacodynamics and pharmacokinetics curves are
disease, chemokine ligand, tau proteins in Alzheimer's disease, plotted for the affinity of binding of drugs to various protein
estrogen receptor. Her-2 EGFR receptor in breast cancer, and biomarkers in the cell lines under investigation. Additionally,
KRAS mutations in colorectal carcinoma. [1,2,4]. Various the role and characterization of biomarkers include markers
scientific committees have proposed the classification and with mutations in proteins in cancerous cells, biomarker
nomenclature for protein biomarkers in organ cancer along with antigens for cancer detection, protein biomarkers in
the significance and role of biomarkers[1]. immunohistochemistry and fluorescent staining of cells and
tissues in pathology. The other roles of biomarkers are
radiolabeled protein biomarkers, quantum dot labelled
biomarkers, biomedical imaging of fluorescent biomarkers in
New pharmacological drugs in-vivo studies of rats, circulating DNA found in tumour cancer
for screening of biomarker cell lines and in the blood of patients and pharmacodynamics
and drug inhibitor response and pharmacokinetics studies of drug-protein biomarker
in cell lines
interaction[14].

3. CASE STUDIES OF BIOMARKERS

The study involves the sample analysis of urine of patients with
cancer as compared to normal urine samples for the analysis of
homovanellate, 4-hydroxy phenyl acetate, the levels of
Drug-docking studies of metabolic products like 5-hydroxyindolyl acetate and urea
protein biomarker inhibitor formedmin the body under two different prevalent conditions.
response in vivo in humans Microarray analysis was performed along with statistical
and mice.
normal distribution analysis of the normal cell samples and
cancer cell patient samples to study the levels of metabolic
analytes. Further breast cancer adenocarcinoma cell samples
were analysed for BRCA gene in patient samples. The analysis
of urine samples was done by gas chromatography and mass
spectroscopy after preparing the samples in the buffer and
digesting them with beta-glucoronidase enzyme [6]. The P-
Binding affinity studies of value was calculated for the intensity of binding in microarray
drugs and proteins example samples along with the study of the levels of tyrosine
for Alzheimer’s disease metabolism analytes in cancer samples and normal samples.
The other study was conducted on ovarian samples of cancer
from patients with the study of random intensity scatter
distribution plots of the genes involved in ovarian cancer
regulation [7].

A study of prostate cancer revealed the levels of sarcosine in

Clinical validation of cancer samples and normal samples along with the study of
inhibitor and drugs used for statistical parameters like mean, median, mode, and area under
targeting cancer. the curve for the intensity profile of the metabolite levels in
samples under study [8]. Further high performance liquid
chromatography was done to purify the sarcosine in the
Fig. 2: The screening of drug-biomarker protein interaction samples under study and to analyse its levels under
is confirmed along with mechanism of action of drugs, experimental observation.
monitoring of effects of interaction of drugs, diagnosis and
treatment of cancers in patients [10].

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 Kharbanda Sulabh; International Journal of Advance Research, Ideas and Innovations in Technology
Table 1: Showing various cancer diseases with biomarkers and their characteristic features.
No. Role Biomarker Characteristics Example disease Author/year
1 Ovarian cancer Carcinogenic embryogenic Present in ovarian cystadenocarcino Sorenson et al., 2011,
antigen A and CA-125 cancer ma Sreeja Sarojini et al., 2012,
(carbohydrate antigen-125) Samimi et al., 2014.
2 Prostate cancer Prostate specific antigen Present in prostate Prostate Chatterjee et al., 2012,
cancer adenocarcinoma Gu et al., 2014,
Meng et al., 2013.
3 Hepatocellular Hepatocyte growth factor Receptor on Hepatocellular Forner et al., 2012,
carcinoma hepatic or liver carcinoma Goodman et al., 2007,
cells Hashem B et al., 2011.
4 Breast cancer HER-2 EGFR receptor The presence of the Breast carcinoma Yu et al., 2012,
cell surface of Tam et al., 2010,
mammary cells Makki et al., 2015.
5 Parkinson Alpha –synuclein, glial Aggregates of Neuronal Jankovic et al., 2014,
disease fibrillary acidic protein proteins in neurons disorder Hauser et al., 2013,
Clebak et al., 2013
6 Alzheimers Tau proteins Aggregates in Neuronal Mattson et al., 2010,
disease neuronal cells disorder Palmer et al., 2011,
Olokoba et al., 2011

4. CONCLUSION [6] Combining tissue transcriptomics and urine metabolomics

The study helps in the analysis of various grades of cancer for breast cancer biomarker identification--Hojung Nam1,
affecting different organs by the study of particular expressions Bong Chul Chung2, Younghoon Kim1, KiYoung Lee3 and
of protein biomarkers in various organs of the body. Various Doheon Lee1—Bioinformatics, Vol. 25 no. 23 2009, pages
methods like immunohistochemistry and fluorescence in situ 3151–3157.
hybridisation were performed to analyse the location and levels [7] Study design and data analysis considerations for the
of biomarkers in cell and tissues under study [1]. There is a discovery of prognostic molecular biomarkers: a case
range of protein biomarkers used for the study of cancers in study of progression-free survival in advanced serous
different organs according to the role of these protein ovarian cancer, Li-Xuan Qin and Douglas A. Levine2, Qin
biomarkers in cell signalling, kinase phosphorylation and and Levine BMC Medical Genomics (2016) 9:27.
transcriptional regulation in tumour and cancerous cells as [8] A case-control study of sarcosine as an early prostate
compared to normal cells [2]. The applications involve the use cancer detection biomarker-Donna P. Ankerst1,2,3*,
of various techniques like mass spectroscopy for the study of Michael Liss2, David Zapata2, Josef Hoefler1, Ian M.
biomarker proteins and their amino acid characterisation in the Thompson2 and Robin J. Leach2,4., Ankerst et al. BMC
sequence along with post-translational modification [2,3]. The Urology (2015) 15:99.
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various cancer samples along with the study of its regulation in Frank, Karl Broich, Stefan J. Teipel, Russell G. Katz, John
the genome[5]. Further microarray analysis was performed to Hardy, Karl Herholz, Arun L. W. Bokde, Frank Jessen,
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cancer genes [7] and antigen prostate-specific antigen in cancer Janet Woodcock & Kaj Blennow.
samples and normal samples as well as sarcosine metabolite [11] Drug targeting to tumours: Principles, pitfalls and (pre-)
samples with statistical analysis [8]. clinical progress, Twan Lammers, Fabian Kiessling, Wim
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