Potentially cancer-causing genes discovered
The study included 20 patients with stages I to III NSCLC, including five non-smokers and 15 smokers. Various genetic testing methods were used to examine lung tumors, uninvolved lung tissue and normal-appearing airways located varying distances from the tumors.
Researchers identified 1,661 differentially expressed gene features between tumors and airways compared with normal lung tissue. A subset of these changes was much more prevalent in lung-cancer patients than cancer-free smokers.
In addition, 422 genes, and key cancer-associated signaling pathways, were progressively expressed in airways, with a more intense presence closer to the tumor and tapering at further distances. This gradient site-dependent effect is consistent with NSCLC expression patterns.
Furthermore, higher levels of LAPTM4B, a gene that has been found in liver, lung, breast, ovarian and gastric cancers, were found in airways closer to tumors. It also aids in autophagy, a self-cannibalization mechanism that helps cells survive. LAPTM4B overexpression can cause resistance to certain types of chemotherapy.
"This is the first time the role of this gene in lung cancer has been studied," Kadara said. "It was highly over-expressed in adjacent normal cells, indicating the possibility of future detection and treatment strategies."
Larger studies of other lung cancer subtypes planned
The research group plans to move forward with more-advanced technology and larger populations to investigate field cancerization in other lung cancer subtypes, such as small-cell lung cancer, in smokers and in lung cancers that develop in non-smokers.
|Contact: Scott Merville|
University of Texas M. D. Anderson Cancer Center