The term biological marker or biomarker refers to a quantified characteristic which may act as a key indicator of a biological condition or a biological state. It can also allude to a substance whose existence indicates the presence of living organisms. In medicine the term can be used for a traceable substance introduced into the system of an organism as a way to examine aspects of health for example organ function. Clinical trials often employ the use of biochemical biomarkers chiefly by deriving them directly from bodily fluids. In genetics biological markers play quite a pivotal role as they are a sequence of DNA associated with disease causation or susceptibility to disease. They are employed in the creation of genetic maps for organisms of interest or organisms under study (Guirgis, Hoda, 2005, p.138). Cell biology also recognizes biological markers as molecules that enable detection and even isolation of a particular type of cells or group of cells. Biological markers may also be used to indicate exposure and longevity of exposure periods or even the effects of xenobiotics which currently are present in organisms and also in the environment. Biological markers also refer to proteins measurable and identifiable in urine or blood or both (Guirgis, Hoda, 2005, p.156). The term is also used to allude to biological molecules often found in body fluids and especially in blood or tissues that act as a sign of abnormal or normal processes in the body.
Biomarkers are extensively used in the detection of cancer cells. A process or a substance that may lead to detection of cancer in the body is known as a cancer biological marker. Molecules secreted by tumors may act as biomarkers (Tonioli, 2008, p.188). The body’s specific reactions to the presence of cancer cells in the body may also act as a biological marker. Imaging, proteomic, glycomic, genetic and epigenetic biological markers may be employed in cancer prognosis, epidemiology and diagnosis. Such biological markers are tested in purely collected biological fluids such as serum or blood (Toniolo, 2008, p.218). In medicine and cancer research the use of biological markers is primarily employed in three ways. Biomarker can be used in a predictive manner to predict the patient’s response level to treatment. Biological markers can also be employed in a diagnostic manner to aid diagnose conditions such as identifying the early stages of cancer.in prognostics biological markers can be used to predict the aggression levels of a condition or foretelling the ability of a patient to fare absent treatment (Miller, Henry, 2004, p.142).
Biomarkers are primarily protein and gene based but may also include a wide range of material found both in the body and in the environment. Micronuclei are also of high significance to carcinogenicism based on recent studies. These extra nuclei may contain fragments of whole chromosomes which after cell division failed to be incorporated into the new daughter cells have been associated with specific cancer forms and are predictors of an extremely poor prognosis. Disrupted micronuclei, highly capable of triggering large scale DNA damage on chromosomes, may play a very active role in the spread of cancer. Studies have also shown that disrupted micronuclei can act as a highly dependable and reliable biological marker for genetic instabilities conspicuous but not exclusive to a large number of solid tumors such as non-small cell lung cancer. The cell division glitch may result in entire chromosomes ending up outside the nucleus. Studies have also shown that appearance of micronuclei is at a higher frequency in cancer cells. Numerous different protein subgroups may also act as biological markers for cancer for example glycoproteins, enzymes, receptors and oncofetal antigens. Other changes that may also occur in tumors may also be used as biological markers for cancer for example changes in microarray generated profiles or genetic signatures, amplifications or translocations and genetic mutations (Homdan, Mahmoud, 2007, p.88). A practical example is the HER2 oncoprotein which recently has emerged as a very pivotal biomarker in breast cancer patient’s treatment. With the removal of the primary breast cancer there is a recurrent and urgent need to detect breast cancer recurrence as soon as possible, hoping that early intervention with new anti HER2 therapies will in overall increase chances of survival and also improve the quality of life. It has been proven that an increase in the level of blood circulating HER2 might just be the earliest indicator of cancer progression particularly and especially in HER2 positive patients. This rise or even fall parallels the clinical course of independent therapy and disease (Homdan, Mahmoud, 2007, p.255). In general a cancer biomarker has to meet certain qualifications. I n prognosis a variety of questions arise key among which is whether it is likely to develop this cancer? In diagnostics the question arises as to what type of cancer it is. In the predictive aspect the question arises as to what is the optimal drug for this particular type of cancer and why. In pharmacodynamics the question arises as to what is the optimal dose for a particular type of body and why. In recurrence study the question as to whether or not the cancer will return must be dealt with in depth and with extremely high levels of thoroughness and comprehensiveness.
Gastric cancer is cancer of the stomach and involves cancerous cells developing in the stomach walls as tumors. Tumors appearing in the stomach are often of two types malignant or benign. Benign tumors do not spread to other body parts. Benign tumors also do not invade the tissues surrounding them and can be removed and usually they never grow back. It is safe to say that benign tumors rarely pose a credible threat to life. Malignant tumors on the other hand warrant a greater deal of concern and worry. These tumors can spread to other parts of the body and they can also not only invade but also damage nearby and surrounding tissues and organs. Malignant tumors can be removed but in some cases they grow back (Kristoff, Helen, 2009, p.208). Malignant tumors undoubtedly pose a credible threat to life. In usual cases gastric cancer normally begins in cells contained in the stomach’s inner layer. The cancer may over time invade deeper into the wall of the stomach. A gastric tumor can grow through the outer layer of the stomach and invade nearby organs including the intestines, the liver, the esophagus and the pancreas. Gastric cancer cells primarily spread by breaking away from the parent tumor and entering the lymph vessels or blood vessels which lead to all the tissues existing in the body. These cancerous cells may attach themselves to other bodily tissues and grow on them to form new tumors that may have a damaging effect on those tissues. When gastric cancer spreads the cancer cells can be found in nearby and surrounding lymph nodes (Kristoff, Helen, 2009, p.238). Adipocytokines which include tumor neurosis factor, lyptin, adiponectin, resistin, type one plasminogen activator inhibitor and hepatocyte growth factor are cytokines which are primarily secreted by visceral adipose tissue and have recently been highly associated with metabolic syndrome. A great number of epidemiologic researches have displayed a positive correlation between obesity and excessive weight and cancer at various areas for example the prostate gland, the colorectum and the endometrium, as well as stomach cancer. These findings have highly suggested that adipocytokines contribute highly to the induction of carcinogenesis and tumor growth and progression. Studies have also suggested that low adiponectin levels can be associated with an increase in the risk of developing gastric cancer. Recent comparisons between normal tissues and stomach cancer tissues has revealed that seven proteins namely transgelin,NSP3,heart shock protein, prohibitin and variant, protein disulphide isomerase A3 and glucose regulated protein were over expressed. Extracellular proteins namely alpha 1 antitrypsin, serum albumin and serotransferrin have been identified as highly under expressed proteins in cancer tissues.
Serial analysis of gene expression has proved to be a powerful technique that allows a genome wide analysis of the expression of genes in a quantitative manner without any prior knowledge whatsoever of the gene sequence (Miller, Henry, 2004, p.318). Extensive studies on samples of gastric cancer each with an entirely different histology and clinical stages have been able to create large and extensive serial analysis of gene expression libraries of stomach cancer that have enabled researchers to identify new cancer biological markers. A comparison of normal gastric genes and genes found in gastric cancer tumors revealed an additional number of genes in the gastric cancer tumors namely CEACAM6, YF13H12 and AOC1. A detailed comparison of gastric cancer genes at early stages and at advanced stages also revealed great disparities between the two. Several genes expressed differently by tumor stage were identified and include COL1A2, FUS, COL1A1 and CDH17 which may be used as genetic markers for cases of high grade malignancy. Studies using RegIV transfected cells have revealed that RegIV is highly secreted by cancerous cells and it in turn inhibits apoptosis. This highly suggests that RegIV can be used as a novel biomarker and therapeutic target for stomach cancer. The production of RNA aptamers could also emerge as a very useful approach to establish a detection system in the blood stream. A combined and detailed analysis of gene polymorphism, gene expression profile and genetic instability will go a long way in aiding both in early cancer detection and also characterization of individual cancer types and cancer patients which will eventually lead to a system of more personalized medication and also a system of early cancer detection and even cancer prevention. In a study to establish the histological classification of gastric cancer several biomarkers such as MSI,KRAS,PIK3CA and H pylori status showed a correlation with either prognosis and phenotype and may be considered for use in tailoring patient treatment in the near future. A molecular description on the highly diverse phases in which gastric cancer occurs is very valuable for better and a more accurate diagnosis and development of therapeutic measures and targets. In past years a ninety two gene classifier that distinguished tumor from non-tumor stomach tissues was proposed and applied (Miller, 2004, p.318). Independent findings and approaches of gene selection and class prediction algorithm were tested and applied to the dataset of eighty six tissues profiled on 17KcDNA microarrays. This resulted in the selection of twenty two genes, eighteen of which proved to be common with the ninety two genes previously provided. The differential patterns of expression of several of the genes that have been proposed have been proven to be very important and necessary for tumor progression in other models of cancer and will, with a very high likelihood, function as novel biological markers for stomach cancer.
A key element that is very essential to the achievement of notable progress in biological marker technology is the industrial ability to screen a very large number of proteins simultaneously in a single experiment with a very high standard of selectivity and sensitivity (Nass, Sharyl, 2007, p.78). There is also a new strategy which makes use of a probe to sort out and distinguish likely proteins. This procedure involves a micro gel which functions in a manner similar to that of a sponge, picking up protein which display a charge or which have a certain mass within a certain range. A method known as mass spectrometry which is a form of analysis which involves molecules being charged and being identified by their mass to charge ratio, can then be used to determine whether a biological marker is present or not in this sample. A major problem with the current techniques of biological marker detection is speed but this new method can significantly reduce and minimize the amount of time required to search for a biological marker in a fluid from several days or even weeks to mere hours. Researchers are currently also working on probes which are capable of selecting not just one type of protein but also a specific given shape of the target protein, rather than mere ranges of size or charge. Research is also being conducted to establish tests that are capable of quantifying levels of a particular protein as opposed to just detecting whether the protein is present or whether it is absent in a given study sample.
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