This document discusses various biomarkers used to diagnose and monitor cancer progression. It describes several common cancer antigen biomarkers like PSA, AFP, CA125, CA15-3, and CEA that are detected in serum to identify prostate, liver, ovarian, breast, and colorectal cancers respectively. Other biomarkers mentioned include hCG for germ cell tumors, thyroglobulin for thyroid cancer, heat shock proteins, glucose metabolism measured via FDG-PET scans, circulating tumor cells, and cancer stem cells. The document provides details on each biomarker's applications, typical values, and utility for cancer diagnosis and prognosis.

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CANCER BIOMARKERS
INTRODUCTION
Every cell type has a unique molecular signature, referred to as biomarkers, which are
identifiable characteristics such as levels or activities (the abilities of genes or proteins to
perform their functions) of a myriad of genes, proteins or other molecular features. Biomarkers
are therefore, an objective measure or evaluation of normal biological processes, pathogenic
processes, or pharmacological responses to a therapeutic intervention1. This includes all
diagnostic tests, imaging technologies, and any other objective measures of a person’s health
status.
The various biomarkers to diagnose the cancer
I. Cancer antigen (biomolecules) based biomarkers:
1. Prostate specific antigen (PSA)
2. Alpha-fetoprotein (AFP)
3. Cancer antigen 125 (CA125)
4. Cancer antigen 15-3 (CA15-3)
5. Cancer antigen 19-9 (CA 19-9)
6. BRCA-1, BRCA-2
7. Carcinoembryonic antigen (CEA)
8. Human chorionic gonadotrophin (hCG)
9. Thyroglobulin (Tg)
10. Heat shock proteins (HSPs) Hsp27; Hsp70
II. Metabolic biomarker
1. Glucose metabolism`
III. Genetic biomarkers
1. APC gene
IV. Cells as biomarker
1. Circulating tumour cells (CTCs)
2. Cancer stem cells (CSCs)
 CA125: The CA 125 antigen is a membrane glycoprotein produced by tissues derived from
coelomic epithelium that is expressed by most epithelial ovarian cancers. CA125 is a powerful
index of risk of ovarian and fallopian tube cancer in asymptomatic postmenopausal women. It is
found in the serum of more than 80 per cent of the patients with epithelial ovarian tumours, with
half life of 4 days. CA-125 antigen remains the only serum tumour marker routinely used in
epithelial cancer of the ovary for patient prognosis, disease progression, and response to
chemotherapy.
Normal values of CA125 in serum range from 0 to 35 U/ ml.

2. CANCER BIOMARKERS
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CA125 are also expressed by a number of tissues of both cancerous and noncancerous origin82.
It may also be elevated in other malignant cancers, including those originating in the
endometrial, fallopian tubes, lungs, breast and gastrointestinal tract. Certain physiological
conditions also modulate CA125 levels, as the levels are elevated slightly during menstruation
and more prominently during the first trimester of pregnancy
 CA15-3: The CA15-3 protein is a member of the family of proteins known as mucins, whose
normal function is cell protection and lubrication. It plays a role in reducing cell adhesion and is
found throughout the body. Elevated levels of this antigen are found mainly in breast cancer
where it appears to be involved in metastasis. CA15-3 level is elevated in nearly 11 per cent of
women with operable breast cancer, and 60 per cent of women with metastatic disease.
Preoperative concentration of CA15-3 is associated with worse prognosis than those with low
concentrations CA15-3 appears to be a marker for individualizing therapy in patients with
breast cancer, where patients with high CA 15-3 show good response to aggressive treatments.
Serum CA15-3 has been used as a surrogate marker of disease bulk to monitor metastatic breast
cancer patients undergoing treatment and for the preclinical detection of tumour recurrence89.
Elevated levels of CA-15-3 has also been found in patients with other cancers (lung, colorectal,
ovarian, pancreatic) and hepatic dysfunction.
Normal level of this marker is 25U/ml.
 Human chorionic gonadotrophin (HCG)
It is a hormone produced normally by the placenta, whose level is elevated in the blood of
patients with certain types of testicular and ovarian cancers (germ cell tumours) and
choriocarcinoma. In addition, synthesis of free βhCG and its subunits by pelvic carcinomas such
as those of the colon, urinary tract, prostate, uterus and vulvo-vagina has also been reported.
The presence of increased serum levels of hCG and its metabolites is generally considered to be
a sign of a poor prognosis and it has been suggested that βhCG might directly modify the
growth of the cancer, leading to a worse outcome. The clinical use of free βhCG as a tumour
marker has been limited to a small number of patients owing to a short half life and rapid renal
clearance. An elevated blood level of hCG is also be found in the urine of pregnant women and
therefore may not be useful as a marker under this condition.
Normal values
Weeks from last menstrual period Normal hCG levels (min/ml)
8-12 32,000-210,000
13-16 9,000-210,000
16-29 14,000-53,000
 Thyroglobulin (Tg)
It is a large glycoprotein stored in the follicular colloid of thyroid gland and acts as prohormone
in the intra-thyroid synthesis of thyroxine (T4) and triiodothyronine (T3). The thyroglobulin test
is primarily used as a tumour marker to evaluate the effectiveness of treatment for thyroid
cancer and to monitor recurrence. Tg is generally measured in serum, but measurements can

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also be made in thyroid cyst fluids and other fluids/tissue obtained by fine needle biopsy of
thyroid nodules. Concomitant measurement of antithyroglobulin is essential as antiTg
antibodies interfere with the Tg assay and render the assay for thyroglobulin in valid. This
important factor should be taken into consideration during the evaluation of patient’s status.
Further, this will not be a very useful marker in tumours which do not release a significant
amount of thyroglobulin into the circulation. Although an undetectable level of serum Tg after
thyroidectomy and ablation suggests that patients are free of disease, several studies have shown
that a minority of patients, under the influence of TSH stimulation, have elevated serum Tg
levels and therefore interpretation needs to be made with caution.
 Heat shock proteins (HSPs)
The expression is tailored for particular stress response, with accumulation of denatured
proteins as the proximal signal for its induction. Heat shock proteins (Hsps) are over expressed
in a wide range of human cancers and are implicated in tumour cell proliferation,
differentiation, invasion, metastasis, death, and recognition by the immune system. At present it
is unclear as to how the Hsps become over expressed in cancer; one hypothesis is that the
physio-pathological features of the tumour microenvironment (low glucose, pH, and oxygen)
stimulate the Hsp induction.
 Glucose metabolism
Enhanced glucose utilization is a prominent and fundamental change in many tumours
irrespective of their histological origin and the nature of mutations, Mechanisms underlying this
fundamental alterations in metabolism during carcinogenesis include mutations in the
mitochondrial DNA resulting in functional impairment, oncogenic transformation linked up
regulation of glycolysis, enhanced expression of metabolic enzymes and adaptation to the
hypoxic tumour micro-milieu in case of solid tumours. Based on these observations, a
bioenergetic index of the cell (BEC index) has been suggested that could be used for
classification and prognosis of cancers, besides predicting the response to therapy. Positron
emission tomography (PET), which allows non invasive and quantitative analysis of various
biologic processes, uses a glucose analogue (2-deoxyD-glucose) labelled with a positron emitter
Fluorine 18; FDG that is partially metabolized and trapped as its phosphate (2-DG-6-P) in the
tumour tissue thus localizing the tumour. The extent of increase in glucose utilization measured
by FDG-PET has been correlated with the degree of malignancy in some of the tumours.
 Circulating tumour cells (CTCs):
It is simple yet powerful biomarker in the field of oncology. The presence of CTCs has been
shown to predict survival in patients with metastatic breast cancer at multiple time points
throughout the course of therapy39. CTCs provide an early, reliable indication of disease
progression and survival for patients on systemic therapy for metastatic breast cancer. Elevated
CTCs at any time during therapy is a harbinger of progression, while elimination of CTCs
indicates effectiveness of the therapy40. Selection of appropriate therapeutic regime can also be
guided by assessment of the presence of the therapeutic target on the CTCs and, in contrast to
CTC scans, the effect of therapy can be measured after the first cycle of therapy. CTCs are not

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only potential surrogate endpoint in oncology clinical trials but may guide the selection of
patients into the trials.
 Cancer stem cells (CSCs):
It has long been recognized that subpopulations of cancer cells exist within the tumours that
resemble the developmental hierarchy of the normal tissue from which the tumour arose. In
recent years, the cancer stem cell model of tumourigenesis has received increasing attention.
This model postulates that tumours are driven and maintained by a minority subpopulation of
cells that have the capacity to selfrenew and to generate the more differentiated progeny which
make up the bulk of a tumour. The former population has been termed cancer stem cells
(CSCs), tumourigenic cancer cells, or tumour-initiating cells, by various investigators, to
indicate that only these can give rise to new tumours when transplanted into immuno-deficient
animals.
CANCER BIOMARKERS FOR DIAGNOSIS AND PROGNOSIS OF THE DISEASE
Biomarker Tumour Applications Sample type/ Method of
detection
Cancer antigen
(biomolecules)
based biomarkers:
Prostate specific
antigen (PSA)
Prostate cancer Diagnosis and
Prognostic
Serum / immunoassay
Alpha-fetoprotein
(AFP)
Hepatocellular
carcinomas
Diagnosis and
Prognostic
Serum / immunoassay
Cancer antigen 125
(CA125)
Ovarian cancers,
fallopian tube cancer
Diagnosis and
Prognostic
Serum / immunoassay
Cancer antigen 15-3
(CA15-3)
Breast cancer Diagnosis and
Prognostic
Serum /ELISA, Lymph
node/ Bone marrow
Cancer antigen 19-9
(CA 19-9)
Pancreatic cancer,
Bladder cancer
Diagnosis and
Prognostic
Serum/ ELISA
Urine/ ELISA
BRCA-1, BRCA-2 Breast cancer Diagnosis and
Prognostic
Tumour samples
Carcinoembryonic
antigen (CEA)
Colorectal cancer Diagnosis and
Prognostic
Serum/ ELISA
Human chorionic
gonadotrophin (hCG)
Ovarian and testicular
cancers
Diagnosis and
Prognostic
Serum / ELISA
Thyroglobulin (Tg) Papillary and
follicular thyroid
cancer
Diagnosis and
Prognostic
Serum / ELISA
Heat shock proteins
(HSPs) Hsp27;
Gastric, prostate
carcinoma,
Diagnosis and
Prognostic
Serum / ELISA

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Hsp70 osteosarcomas,
uterine, cervical, and
bladder carcinoma
Metabolic biomarker
Glucose
metabolism
All cancers, general Diagnosis and
Prognostic
Imaging/ FDG – PET scan
Genetic biomarkers
APC gene Adenocarcinoma,
squamous cell
carcinoma of the
stomach, pancreas,
thyroid and ovary
Diagnosis and
Prognostic
Blood, tumour samples,
methylatiom of status of
APC gene
Cells as biomarker
Circulating tumour
cells (CTCs)
Metastatic breast
cancer
Diagnosis and
Prognostic
Blood/ Immunocytometry
Cancer stem cells
(CSCs)
AML, melanoma,
brain tumour,
prostate cancer
Diagnosis and
Prognostic
Tumour samples/
Immunocytometruy
CASE STUDY RELATED TO CANCER BIOMARKERS
CASE STUDY ON OVARIAN TUMOR WITH STAGES – II BREAST
CANCER
SUBJECTIVE: A 50yrs old female patient was admitted in female medical ward in
vishwabharathi hospital with the chief complaints of
 Pain in abdomen since 1 month.
 Post menopausal bleeding since 3months.
 Pain and mass over lower abdomen.
LABORATORY INVESTIGATION:
TEST OBSERVED VALUE REFERANCE VALUE
WBC 12000*IU/L 4500 – 11000 IU/L
HB 12.3*gm/dl 13.0-18.0gm/dl
T3 57.14*mg/dl 80-200 mg/dl
T4 15.4* mg/dl 5.1-14.1 mg/dl
Random blood sugar 100 mg/dl 80-130 mg/dl
Serum creatitine 1.0 mg/dl 0.60-1.50 mg/dl
CA -125 level 20* IU/ml 0 – 3.5 IU/ml

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PREVENTIVE MEASURES FOR OVARIAN CANCER:
• Follow regular medications as prescribed by the physician.
• Maintain normal glucose levels.
• Maintain normal blood pressure.
• Use of essential oils, lavender oils for the relive of pain.
• TENS therapy should be preferred.
• Leboyers Therapy also used.
• Touch and massage the area where the pain is observed.
• Closely and carefully monitor the maternal movements and position of the fetus.
• Maintain sedentary life style modifications.
• Have your partner always use condoms during sex.
• Don‘t have sex with a partner who has genital sores or penile discharge.
• Avoid sex with multiple partners.
• Don’t use feminine hygiene products. These may causes irritation of your vagina and
cervix.
• If you have diabetes, try to maintain good control of your blood sugar.
• Maintain healthy diet.
• Exercise regularly.
References
1.Srinivas PR, Kramer BS, Srivastava S. Trends in biomarker 1. research for cancer
detection. Lancet Oncol 2001; 2 : 698704.
2.Cho WSC. Contribution of oncoproteomics to cancer 2. biomarker discovery. Mol Cancer
2007; 6 : 25.
3. Hanahan D, Weinberg RA. The hallmarks of cancer.3. Cell 2000; 100 : 57-70.
4. https://www.healthline.com/health/thyroid-function-tests
PRECEPTOR’S SIGNATURE: