Human saliva is an ideal body fluid for developing non-invasive diagnostics. Saliva contains naturally-occurring nanoparticles with unique structural and biochemical characteristics.

1. DIAGNOSIS OF CANCER THROUGH
SALIVA
There are many advantages of using saliva as a biofluid. Its collection is
fast, easy, inexpensive, and non-invasive. In addition, saliva, as a
"mirror of the body," can reflect the physiological and pathological
state of the body. Therefore, it serves as a diagnostic and monitoring
tool in many fields of science such as medicine, dentistry, and
pharmacotherapy. Introduced in 2008, the term "Salivaomics" aimed
to highlight the rapid development of knowledge about various
"omics" constituents of saliva, including: proteome, transcriptome,
micro-RNA, metabolome, and microbiome.
Major areas of salivary diagnostics.

2. INTRODUCTION
Human saliva is an ideal body fluid for developing non-invasive
diagnostics. Saliva contains naturally-occurring nanoparticles
with unique structural and biochemical characteristics. The
salivary exosome[proteins, microRNAs (miRNAs), and
messenger RNAs (mRNAs)], a nanoscale extracellular vesicle, has
been identified as a highly informative nanovesicle with clinically-
relevant information. Salivary exosomes have brought forth a
pathway and mechanism by which cancer-derived biomarkers
can be shuttled through the systemic circulation into the oral
cavity. Characterization of individual exosome nanostructures
provides critical data for understanding their pathophysiological
condition and diagnostic potential. Structural characteristics of the human salivary exosome at the single-
vesicle level. (a–c) AFM topographic (z = 0–10 nm), amplitude, and phase
images of salivary exosomes from healthy donors. The exosomes appear
as homogeneous circular structures with a distinct phase contrast between
the less dense periphery and the denser core region. (d–f) Exosomes
from an oral cancer patient show an irregular morphology with varying
shapes and vesicle aggregation (arrows). (e) The amplitude image shows
the clumping of vesicles. (f) In the phase image, the larger vesicles appear
hollow (arrows) without the dense core region typically seen in normal
exosomes. All images were obtained over mica substrates under ambient
conditions. Reprinted with permission from [107]. Copyright 2011,
American Chemical Society

3. BIOMARKER -miRNA(micro RNA )
• MicroRNAs (miRNAs or miRs) are short non-coding RNA molecules (about 19–23 nucleotides long) that are involved in the
regulation of gene expression at transcriptional and post-translational levels.
• miRNAs constitute one of the most abundant classes of gene-regulatory molecules. They are consistently part of the
transcriptome and their biological influence is widespread; over 30% of the genome is predicted to be actively regulated by
miRNAs, and it has been shown that they are involved in the regulation of gene expression and in a variety of cell processes
such as apoptosis, proliferation, and differentiation.
• The aberrant expression of microRNAs (miRNAs) has been associated with several diseases, including cancer, inflammatory,
and autoimmune conditions.
• Genetic alterations such as chromosomal rearrangements, genomic amplifications, deletions, or point mutations
presumptively play an important role in disease initiation and progression through the aberrant expression of miRNAs located
in the affected regions and, subsequently, by deregulation of their downstream mRNA targets. Gene regulation and gene
expression are obtained through miRNA binding to the 30 -UTR (untranslated region) of mRNAs and the consequent
degradation or translational repression of targeted gene transcripts
• The possibility of evaluating miRNAs in “liquid biopsy” has made rapid progress since 2008, when circulating miRNAs were
detected for the first time in the blood of patients with diffuse large B-cell lymphoma and prostate cancer
• Circulating miRNAs have subsequently been found in several other body fluids, including urine, saliva, and cerebrospinal
fluid. The detection of these small molecules in a surprisingly stable form is due to their association with subcellular vesicle-
free particles (usually protein complexes) or to the packaging into micro-vesicles or exosome

4. CURRENT DETECTION METHOD OF CANCER .
 CT ( computerized tomography ) scan
o Bone scan
o Magnetic resonance imaging ( MRI ) scan
o Position emission tomography ( PET ) scan
o Ultrasound
o X – ray
What problem are we trying to solve ?
 The aberrant expression of miRNAs has been associated with a growing number of disease states, including
cancer, inflammatory, and autoimmune diseases .
 Saliva has a very complex composition, including enzymes, antibodies, hormones, antimicrobial elements,
and cytokines. For liquid biopsy, saliva presents many advantages over blood, with its collection being easy,
safe, non-invasive, and cost-effective.
 Salivary diagnostics have disclosed the existence of several molecular indicators of local and systemic
disorders, including cancer

5. DIFFERENT TYPE OF CANCER IS IDENTIFY BY DIFFERENT TYPES OF BIOMARKER
BREAST CANCER
Breast cancer is one of the most common cancers in females. ATP6AP1 is an ATPase that is
expressed in normal tissues such as the brain marrow, blood, nerves and skin, and it is also
correlated with several tumors such as head and neck carcinomas, lung tumors, adrenal
tumors and various other cancers. Nevertheless, its prevalence in breast cancer is the greatest
among these cancers. ATP6AP1 auto antibodies are spontaneously generated in patients and they
can be detected in early stages. Thus, it is indicated that ATP6AP1 can contribute to the early
detection of breast cancer. It has been found that eight mRNA biomarkers and one protein
biomarker that could be used to detect breast cancer with an 83% sensitivity and 97% specificity.
In another study, it was found that the levels of vascular endothelial growth factor, epidermal
growth factor (EGF) and carcinoembryonic antigen in the saliva were significantly increased in
patients with breast cancer. The levels of CA15-3 and c-erB-2 were also found to be increased in
the saliva, which has positive correlations with the serum of patients with breast cancer. Based on
these studies, potential salivary biomarkers can be applied to the early diagnosis of breast cancer.

6. ORAL CANCER
Oral cancers are the sixth most frequent cancer with a high mortality rate. Oral squamous cell carcinoma accounts for more than
90% of all oral cancers. Saliva's direct contact with oral cancer lesions makes it more specific and potentially sensitive screening
tool, whereas more than 100 salivary biomarkers (DNA, RNA, mRNA, protein markers) have already been identified, including
cytokines (IL-8, IL-1b, TNF-α), defensin-1, P53, Cyfra 21-1, tissue polypeptide-specific antigen, dual specificity phosphatase,
spermidine/spermineN1-acetyltransferase , profilin, cofilin-1, transferrin, and many more.
The onset and development of malignancy are related to somatic mutations of tumour-specific DNA, which can be found in the
saliva, plasma or other body fluids. These somatic mutations can be used as biomarkers to diagnose oral or other tumours. In
saliva, tumour specific DNA was positive in 100% of patients with oral tumours. However, only 47%–70% of patients with
tumours in the other parts of the human body carry tumour-specific DNA in the saliva. In contrast, tumour-specific DNA was
found in 80% of plasma samples from patients with oral tumours and in 86%–100% of patients with tumours in other sites. Based
on these results, saliva has an overabundance of tumour-specific DNA from oral tumours. Thus, tumour-specific DNA in saliva
has the potential to be applied to diagnose oral cancers. The DNA of tumour-related viruses in saliva, such as HIV and human
herpes virus (HHV), can also be associated with cancers of the oral cavity or other sites. It is found that miR-125a and miR-200a
levels were of great significance as follows: compared with healthy individuals, patients with oral squamous cell carcinoma
(OSCC) have lower levels in their saliva, indicating that miRNAs in saliva have a potential application in oral cancer detection.
Salivary proteins can also be used for cancer detection. It was reported that the increase in tumour antigen CA15-3 and
antibodies for tumour protein markers c-erbB2, CA-125 and P53 in saliva can also be considered salivary biomarkers for cancers
of the oral cavity and other sites. Further studies showed that hyaluronidase, IL-6 and IL-8 might be potential biomarkers for
patients presenting with head and neck squamous cell carcinoma (HNSCC).

7. LUNG CANCER
Lung cancer has a high incidence rate. Mutations
identified in the EGF receptor (EGFR) are the tumor-
specific biomarkers for non-small cell lung
carcinoma (NSCLC). A novel core technology known
as electric field-induced release and measurement
relies on a multiplexable electrochemical sensor
that can detect EGFR mutations in bodily fluids was
shown to be effective, accurate, rapid and cost
effective for the detection of EGFR mutations in the
saliva of patients with NSCLC. In addition, Xiao et al.
found 16 candidate proteins that can discriminate
lung cancer patients from healthy individuals and
are effective biomarkers with a high sensitivity and
specificity. This demonstrates that proteomic
biomarkers can be established for the early
detection and prognosis of lung cancer.
Electric field–induced release and measurement (EFIRM) technology for the
detection of epidermal growth factor receptor (EGFR) mutations in bodily fluids
of patients with lung cancer.

8. GASTRIC & PANCREATIC CANCER
• Evidence exists that salivary miR-940 and miR-3679-5p are reliable markers for pancreatic
cancer and that miR140-5p and miR301a are promising molecules for the salivary diagnosis of
gastric cancer.
• Evidence exists that several salivary biomarkers (including genetics, transcription molecules,
proteins, metabolites, and lipids) can accurately describe peculiar pathological and
physiological states. Examples of diseases that can reliably be diagnosed through salivary
analysis are pancreatic (miR-3679-5p and miR-940), lung (cytokines IL1RN, IL1B, CXCL10), and
breast cancers (phenylalanine, tryptophan) , as well as myocardial infarction (C-reactive
protein, myoglobin, and myeloperoxidase).
• Among salivary biomarkers, miRNAs seem very promising, both for early diagnosis and for
understanding the pathogenesis of some diseases (e.g., oral cancer, salivary glands cancer,
neurological or psychiatric deficiencies).

10. CONCLUSION
The advantages of saliva as a diagnostic fluid are that it is simple to collect, convenient to
store, essentially non-invasive and contains high-quality DNA.
Thus, we conclude that saliva is a perfect substitute for blood. The research in salivaomics
has an important role in identifying biomarkers of diseases and potential drug targets.
Salivaomics also has the potential to diagnose diseases in their early stages.
However, research on saliva and its applications for the diagnosis of disease is still in its
early stages and the progress of these studies is limited by the lack of efficient and useful
methods and techniques.
We need to develop systems of salivary molecular identification and standardize salivary
evaluation. Systemic knowledge networks of salivaomics and precise biomarkers of
diseases can contribute to a better understanding of the correlations between oral health
and systemic health, which will promote the application of precision medicine by
facilitating the individualization of precise, pain-free and convenient targeted therapy.

11. REFERENCE
IJMS | Free Full-Text | Salivary MicroRNA for Diagnosis of Cancer and Systemic Diseases: A Systematic
(mdpi.com)
Saliva in the diagnosis of diseases (nature.com)
Full article: Proteomic analysis of saliva for cancer diagnosis (tandfonline.com)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5447327/
https://pubmed.ncbi.nlm.nih.gov/29054268/
https://pubmed.ncbi.nlm.nih.gov/27903834/
https://www.hspp.ucla.edu/publications
MADE BY- ZAID AHMAD