Gastric cancer susceptibility marker discovered

December 17, 2019

Gastric cancer, the third most common cause of cancer-related deaths, is often associated with a poor prognosis because it tends to be diagnosed at an advanced stage and is therefore difficult to treat. To reduce the death rate, it is essential to identify a biomarker enabling early diagnosis of this cancer. In pursuit of this goal, scientists from the Institut Pasteur, CNRS, and University of Rennes 1 working in partnership with the IMSS in Mexico and the University of Florence in Italy, analyzed the mechanisms involved in the development of gastric cancer during infection by the bacterial pathogen Helicobacter pylori. As a result, they were able to identify a potential susceptibility marker. Their findings were published in the journal Gut on December 10, 2019.

Helicobacter pylori is a bacterial pathogen that colonizes the stomachs of almost half the world's population. H. pylori infection is acquired in childhood and lasts for decades. While remaining asymptomatic in most individuals, in some cases the infection develops into gastric cancer. H. pylori is currently thought to be responsible for approximately 90% of gastric cancer cases throughout the world, with an estimated death rate of approximately 800,000 per year.

The first steps have been taken toward deciphering the sequence of events triggered by bacterial infection ultimately leading to gastric cancer, a mechanism in which infected cell DNA instability plays a key role. Previous studies have demonstrated that H. pylori causes DNA breaks and impairs the DNA repair systems by stimulating the accumulation of mutations potentially targeting p53, a protein known as the "guardian of the genome".

Protein p53 is essential for proper cell function since, if significant damage occurs within the genome, it temporarily stops the cell cycle for a sufficient period of time to repair DNA. If p53 is inactivated, the genome is therefore more likely to accumulate instabilities, and normal cells have a greater chance of transforming into cancer cells. It is important to understand cellular transformation caused by H. pylori, which stimulates cancer development, in order to identify a susceptibility marker. This would enable early treatment of patients, thus preventing the development of gastric cancer.

In vitro, in vivo, and clinical testing

The group led by Marie-Dominique Galibert, a scientist at the Rennes Institute of Genetics and Development (University of Rennes 1/CNRS) previously conducted studies revealing that, in response to DNA damage, p53 is stabilized by its interaction with the transcription factor USF1, thus enabling p53 to play its role in DNA repair. However, in vitro results from this publication relating to cell lines demonstrate that H. pylori not only reduces nuclear levels of factor USF1, but also relocates it, leading to its accumulation at the periphery of cells, thus preventing the formation of USF1/p53 complexes in the cell nucleus. If destabilized, protein p53 loses its function, resulting in accumulated oncogenic changes in infected cells, promoting their transformation into cancer cells. Therefore, the loss of USF1 from the nucleus is a key factor in inhibiting p53 activity, which stimulates the development of gastric cancer.

These findings have been confirmed by in vivo studies. Scientists demonstrated that gastric inflammatory lesions caused by H. pylori infection were more severe in a mouse model deficient in factor USF1. These results are also supported by clinical findings, since the prognosis is worse for gastric cancer patients with low levels of USF1 combined with low levels of p53.

These data provide a new conceptual basis for improving patient management. Indeed, variations in USF1 levels in gastric tumor tissue could be an indicator of poor prognosis in cases of gastric cancer, thus enabling subsets of patients at higher risk or with more severe forms of cancer to be identified.

Eliette Touati, joint last author of the article and scientist within the Helicobacter Pathogenesis Unit (Institut Pasteur/CNRS), concludes: "For the first time, we have demonstrated that the loss of transcription factor USF1 accelerates carcinogenesis caused by Helicobacter pylori. This makes USF1 a potential biomarker for gastric cancer susceptibility and a new therapeutic target in the treatment of this cancer."
This work was funded by the research organizations mentioned above and also by Odyssey Reinsurance Company, the French Cancer League (LNCC), the Biosit joint service unit (UMS), and the Fondo de Investigacion en Salud (IMSS).

Institut Pasteur

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to