Study Examines Gene Expression of Adjacent Airway Field Cancerization in NSCLC
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 that the area adjacent to tumors 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.
“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,” said study lead author Humam Kadara, PhD, Assistant Professor, Translational Molecular Pathology at MD Anderson.
Field Cancerization May Yield Answers
It is known that cigarette smoke induces widespread cellular changes and premalignant lesions in the lungs of smokers. However, symptoms of lung cancer usually don’t appear until the disease is advanced and untreatable. Although it’s believed to start as precancerous changes in the lung, little is known about those changes that lead to lung cancer.
Field cancerization is a phenomenon in which large areas of cells are affected by a cancer-causing event, such as smoking. Previous research has shown that normal-appearing tissue close to lung premalignant and cancer lesions may have tumor-associated molecular abnormalities. This study is the first effort to comprehensively examine gene expression, known as the transcriptome, of the adjacent airway field cancerization in NSCLC.
Potentially Cancer-Causing Genes Discovered
The study included 20 patients with stage I to III NSCLC, including five nonsmokers 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 patients with lung cancer than in cancer-free smokers.
In addition, 422 genes along with 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. LAPTM4B also aids in autophagy, and overexpression of the gene can cause resistance to certain types of chemotherapy.
“This is the first time the role of this gene in lung cancer has been studied,” Dr. Kadara said. “It was highly overexpressed in adjacent normal cells, indicating the possibility of future detection and treatment strategies.”
Larger Studies 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 nonsmokers.
“We’re just beginning to understand the relevance of airway field cancerization to lung cancer detection and development of treatment and prevention strategies,” Dr. Kadara said.
Ignacio I. Wistuba, MD, of The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of the National Cancer Institute study.
The study was funded in part by grants from the Lung Cancer Research Foundation, the Jimmy Lane Hewlett Lung Cancer Research Fund, National Cancer Institute, the Department of Defense, and MD Anderson’s NCI Cancer Center Support Grant.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
