How early breast tumors become deadly: A small group of molecules might hold the answer
Researchers have discovered a restricted pattern of molecules that differentiate early-stage breast tumors from invasive, life-threatening cancer. They also found a similar molecular signature that correlated with the aggressiveness of invasive tumors, and with the time to metastasis and overall survival.
Investigators at the Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC James) who led the study say the findings could offer new strategies for treating breast cancer by blocking progression to life-threatening invasive cancer.
The researchers investigated a common type of early-stage breast cancer called ductal carcinoma in situ (DCIS). DCIS tumors are confined to the milk duct, and, though small, they are detectable by mammography. They can sometimes grow and spread beyond the milk duct into surrounding healthy tissue, a stage called invasive ductal carcinoma.
The study, reported in the Proceedings of the National Academy of Sciences, compared the pattern of molecules called microRNAs in DCIS to the pattern present in invasive ductal cancer. It identified nine microRNAs that distinguished invasive cancer from DCIS.
"The transition from DCIS to invasive ductal cancer is a key event in breast cancer progression, but it remains poorly understood," says principal investigator Dr. Carlo M. Croce, director of Ohio State's Human Cancer Genetics program and a member of the OSUCCC James Molecular Biology and Cancer Genetics program.
"These findings suggest that this 'micro-signature' might be used to identify DCIS tumors that are at high-risk for becoming invasive cancer."
MicroRNAs are a class of molecules that help control the types and quantity of proteins cells make. Work by Croce and others has shown that microRNAs are often dysregulated during cancer development, and it has suggested that the molecules offer new biomarkers of disease, and that restoring key microRNAs to normal levels might offer a new approach to cancer treatment.
First author and cancer researcher Dr. Stefano Volinia notes that high expression of one of those molecules, called miR-210, correlates with tumor aggressiveness and with time to metastasis and overall survival.
"If we could inhibit the few miRNAs associated with tumor invasiveness, perhaps we could arrest tumor progression at the harmless, pre-invasive state," says Volinia, an assistant professor of molecular virology, immunology and medical genetics and of biomedical informatics.
For this study, Croce, Volinia and their colleagues studied microRNA profiles from data collected using whole-genome deep sequencing. They examined 80 cases of invasive ductal carcinoma, eight of DCIS, and six of normal breast biopsies.
Comparing DCIS and invasive cancer samples showed nine microRNAs that formed an "invasiveness micro-signature." Three of these miRNAs (let-7d, miR-210, and -221) showed the most extreme changes in expression levels. Relative to their levels in normal breast tissue, the three were down-regulated in DCIS, then up-regulated in invasive cancer.
"That told us that progression from in-situ ductal cancer to invasive cancer involves a reversal of miRNA expression," Croce says.
Journal reference: Proceedings of the National Academy of Sciences
Provided by Ohio State University Medical Center
- Protein predicts development of invasive breast cancer in women with DCIS May 22, 2009 | not rated yet | 0
- Precancer? Earliest cancer? Milk-duct cells vexing Sep 24, 2009 | not rated yet | 0
- PINC trial launched to test new treatment for pre-invasive breast cancer Mar 02, 2010 | not rated yet | 0
- Cells lining milk ducts hold key to spread of common form of breast cancer May 05, 2008 | not rated yet | 0
- DCIS patients who get invasive breast cancer have higher mortality Mar 12, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
The use of a smartphone application significantly improves patients' preparation for a colonoscopy, according to new research presented today at Digestive Disease Week (DDW). The preparation process, which begins days in ...
Cancer 8 hours ago | not rated yet | 0
Research presented at Digestive Disease Week (DDW) explores new methods for managing digestive health through diet and lifestyle.
Cancer 8 hours ago | not rated yet | 1
A ground-breaking advance in colonoscopy technology signals the future of colorectal care, according to research presented today at Digestive Disease Week(DDW). Additional research focuses on optimizing the minimal withdrawal ...
Cancer 23 hours ago | 5 / 5 (2) | 0
(HealthDay)—Concurrent use of two immune checkpoint antibodies—ipilimumab and nivolumab—may be effective for the treatment of advanced melanoma, according to a proof-of-principal study presented in ...
Cancer May 17, 2013 | not rated yet | 0
(HealthDay)—The risks of metastasis and death associated with cutaneous squamous cell carcinoma (CSCC) are low, but significant, and risk factors for poor outcome include tumor diameter, invasion beyond ...
Cancer May 17, 2013 | not rated yet | 0 |
The hunt for an HIV vaccine has gobbled up $8 billion in the past decade, and the failure of the most recent efficacy trial has delivered yet another setback to 26 years of efforts.
1 hour ago | not rated yet | 0
Regular consumption of coffee is associated with a reduced risk of primary sclerosing cholangitis (PSC), an autoimmune liver disease, Mayo Clinic research shows. The findings were being presented at the Digestive Disease ...
9 hours ago | not rated yet | 0 |
Patients with treatment-resistant major depression saw dramatic improvement in their illness after treatment with ketamine, an anesthetic, according to the largest ketamine clinical trial to-date led by researchers from the ...
9 hours ago | 4.5 / 5 (2) | 0 |
An increasing number of U.S. children are experiencing gastrointestinal issues that require interventions to resolve, according to research presented at Digestive Disease Week (DDW).
23 hours ago | not rated yet | 0 |
There are significant cost and risk factors associated with two procedures commonly used to diagnose or treat gastrointestinal problems, according to research presented at Digestive Disease Week (DDW).
8 hours ago | not rated yet | 0