Seemingly healthy cells may in fact hide clues that lung cancer will later develop, according to a study led by researchers at The University of Texas MD Anderson Cancer Center. The research is published online in the Journal of the National Cancer Institute.
Examination of gene expression in patients with non-small cell lung cancer (NSCLC) showed the area adjacent to tumours is rich with cancer markers. In addition, researchers discovered the previously unknown role of a cancer-promoting gene in the airways of smokers with lung cancer.
“We believe this study has a “double whammy” application,” said study lead author Humam Kadara, Ph.D., assistant professor, Translational Molecular Pathology at MD Anderson. “These cancer-associated changes that distinguish the airways of smokers with lung cancer and healthy smokers may help us diagnose lung cancer earlier and develop more effective strategies for treatment.”
Field carcinogenesis may yield answers
Field carcinogenesis is a phenomenon in which large areas of cells are affected by a cancer-causing event, such as smoking. This is the first effort to comprehensively examine gene expression, known as the transcriptome, of the adjacent airway field carcinogenesis in NSCLC.
Previous research, including pioneering work at MD Anderson by this study’s senior author Ignacio Wistuba, M.D., and others, has shown normal-appearing tissue close to lung premalignant and cancer lesions may have tumour-associated molecular abnormalities. And it’s known cigarette smoke induces widespread cellular changes and premalignant lesions in the lungs of smokers.
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 tumours, uninvolved lung tissue and normal-appearing airways located varying distances from the tumours.
Researchers identified 1,661 differentially expressed gene features between tumours 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 signalling pathways, were progressively expressed in airways, with a more intense presence closer to the tumour 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 tumours. 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 carcinogenesis in other lung cancer subtypes, such as small-cell lung cancer, in smokers and in lung cancers that develop in non-smokers.
“We’re just beginning to understand the relevance of airway field carcinogenesis to lung cancer detection and development of treatment and prevention strategies,” Kadara said.
Source: The University of Texas MD Anderson Cancer Center