Higher Score of Markers Spell Poor Prognosis of Cancer

A set of 14 genes have been identified which could act as biomarkers for cancer prognosis, higher the score worse the prognosis.

Highlights

Centromere gene expression score (CED) identified as key biomarker for cancer.
High CES signals poor prognosis
High level of chromosome instability leads to better response to adjuvant therapy

Researchers from The Lawrence Berkeley National Laboratory’s Department of Energy have found clues to using genetic biomarkers to study the need for adjuvant therapy like chemotherapy or radiotherapy in the treatment of cancer. This is meant to allay fears associated with excessive treatment meted out to cancer patients.

Scoring System for Cancer Prognosis

The University of Berkeley researchers found 14 genes that were over expressed in various types of cancer and they developed a scoring system that could identify the prognosis of cancer. The scoring system that these researchers developed aided in identifying these two factors

In some forms of cancer like in lung cancer or breast cancer, a high score could signify poor prognosis.
The scoring system could be used to accurately determine the response of patients to cancer treatments.

The necessity to develop diagnostic methods to discern the need for cancer treatments stems from the use of chemotherapy even in early stage lung cancer where the effectiveness of the treatment is merely 10% but the patient could be weighed down by the side effects of treatment.

Stem Cells Propagation and Cancer Risk
Cancer cells are found to be stem cells that have been activated by DNA mutation and tissue damage according to study by Cambridge University researchers.

‘High level of chromosome instability will lead to better response to adjuvant therapy in cancer patients.’

The study's principal investigator who is a researcher with The University of Berkeley’s Department of Molecular and Cell Biology and department of Biological Systems and Engineering, Dr. Gary Karpen said “The history of cancer treatment is filled with overreaction. It is part of the ethics of cancer treatment to err on the side of overtreatment, but these treatments have serious side effects associated with them. For some people, it may be causing more trouble than if the growth was left untreated."

Side Effects of Chemotherapy

Cancer cells are essentially the body’s own cells, which is why the body’s immune system is unable to fight against the cancer cells. In chemotherapy, growing, active cells are targeted in a bid to kill all cancer cells. As a result, other active and growing cells of the body are also killed which include cells in the blood, mouth and hair follicles.

Genetic Biomarker May Predict Side Effects Associated with Prostate Cancer Treatment
Taxanes are a group of drugs commonly used to treat cancers of the breast, lung, ovary, or prostate, but its use can be limited by significant side effects.

The patients could suffer from:

Pain
Nausea
Vomiting
Lowered immunity
Anemia
Numbness or weakness in the leg
Sores in the mouth
Nervous problems that could result in an inability to walk properly or feeling of being disoriented.
Loss of memory

The extent of side effects depends on the duration of chemotherapy, the health of the individual and the drugs used for chemotherapy.

Side Effects of Radiation Therapy

Prevention of Genetic Breast Cancer by Blocking a Bone Gene
Genetically determined breast cancer can be largely prevented by blocking a bone gene, revealed an international team led by researchers.

Radiation therapy is the use of radiation to kill possible cancer cells at the site of cancer development. The extent and type of side effects depend on the site of cancer and the health of the individual.

Stiffness of the jaw
Shortness of breath
Nausea
Vomiting
Diarrhea

Dr. Anshu Jain who is an oncologist at Ashland Bellefonte Cancer Center and is the co-author of the study said that the discovery of these biomarkers was “very exciting” and that the "The biomarker score provides predictive and prognostic information separate from and independent of clinical and pathologic tumor characteristics that oncologists have available today and which often provide only limited clinical value."

Genes that Regulate Centromere and Kinetochores

The team of Berkeley University researchers found a particular centromere protein was over expressed in fruit flies which led to additional attachment sites. The significance of studying these additional centromeres is given by Dr. Karpen "This essentially makes new centromeres functional at more than one place on the chromosome, and this is a huge problem because the spindle tries to connect to all the sites. If you have two or more of these sites on the chromosome, the spindles are pulling in too many directions, and you end up breaking the chromosome during cell division. So over expression of these genes may be a major contributing factor to chromosomal instability, which is a hallmark of all cancers."

Gene Mutation Hotspots Linked to Breast Cancer
Kataegis is a recently discovered phenomenon in which multiple mutations cluster in a few hotspots in a genome.

Role of Centromeres in Chromosome Instability

Though the presence of a large amount of chromosome instability in cancers is well known, the effect of centromeres in chromosome instability has never been studied. The researchers accessed information from The Broad Institute, National Center for Biotechnology Information and other institutions and analyzed data from thousands of human tumors from more than 12 types of cancers. The researchers studied 31 genes for their role in tumorigenesis.

14 genes were over expressed consistently in cancers.
The kinetochore gene expression score strongly correlated with whether the patient survived after 5 years.
The presence of a high number of these genes indicated that the patient would respond better to chemotherapy and radiotherapy.
With respect to chromosome instability

Presence of low to medium level of chromosome instability could make the cancer thrive.
High level of instability makes the cancer cells more susceptible to cancer treatment.

The kinetochore gene expression score (CES) will have a significant impact on doctor recommendation for chemotherapy and radiation for cancer patients. In future, after detailed studies, it could be used to determine the course of treatment. The researchers were unable to find a correlation between high chromosome instability and improvement in patient survival without any adjuvant therapy.

There are a number of studies that are carried out to improve treatment options for cancer and to understand the mechanism of cancer development. The presence of a set of guidelines or a benchmark using the CES could soon save some cancer patients from unnecessary adjuvant treatment which give rise to side effects.

References:

Side Effects of Chemotherapy - (http://www.cancer.net/navigating-cancer-care/how-cancer-treated/chemotherapy/side-effects-chemotherapy)
Radiotherapy side effects - (http://www.cancerresearchuk.org/about-cancer/cancers-in-general/treatment/radiotherapy/side-effects/)

Source-Medindia