An analysis of genetic and clinical data for nearly 800 patients with non-small cell lung cancer has identified differences in genetic characteristics that are associated with age and sex specific patterns of increased or decreased recurrence-free survival, according to a study in the February 10 issue of JAMA.
The five-year overall survival rate for lung cancer is only 15 percent, and it remains the leading cause of cancer-related death in the United States. An estimated 159,000 lung cancer deaths occurred in 2009, and more than 219,000 new cases were diagnosed. Almost half of these new cases are diagnosed in women, with approximately 30 percent to 40 percent of cases diagnosed in patients older than 70 years, with the majority of these cases (greater than 85 percent) non-small cell lung cancer (NSCLC), according to background information in the article.
"Despite evidence that clinical and pathologic factors (e.g., age, histology, smoking status, sex) are clinically relevant, little is known regarding the underlying biological differences in lung tumor gene expression among patients with different clinicopathologic characteristics. A deeper understanding of molecular abnormalities at a pathway level [involving gene expression and biochemical reactions that transmit information within and between cells] may help dissect the complex mechanisms of lung cancer oncogenesis [development of tumors], shed light on the biological underpinnings contributing to survival differences in NSCLC that are age- and sex-based, and further help identify specific cohorts of patients that may be more susceptible to novel individualized therapeutic strategies," the authors write.
William Mostertz, M.S., of Duke University, Durham, N.C., and colleagues examined clinically relevant differences in the underlying biology of NSCLC based on patient age and sex. The study consisted of an analysis, performed from July 2008 to June 2009, of 787 patients with predominantly early stage NSCLC. Lung tumor samples with corresponding microarray (genetic analysis of biological material) and clinical data were used. All patients were divided into subgroups based on age (less than 70 vs. 70 years or older) or sex.
Low- and high-risk patient clusters/groups were identified with the longest and shortest 5-year recurrence-free survival, respectively, within the age and sex NSCLC subgroups. The researchers found that these cohorts of NSCLC demonstrated unique patterns of pathway activation. In patients younger than 70 years, high-risk patients, with the shortest recurrence-free survival, demonstrated increased activation of the Src (a gene) (25 percent vs. 6 percent) and tumor necrosis (death of cells or tissue) factor (76 percent vs. 42 percent) pathways compared with low-risk patients. High-risk patients ages 70 years or older demonstrated increased activation of the wound healing (40 percent vs. 24 percent) and invasiveness (64 percent vs. 20 percent) pathways compared with low-risk patients.
The researchers found a difference in the biology of lung cancer between men and women. "In women, high-risk patients demonstrated increased activation of the invasiveness and STAT3 [a gene] pathways while high-risk men demonstrated increased activation of the STAT3, tumor necrosis factor, EGFR [epidermal growth factor receptor; a protein that plays a role in causing cells to grow and multiply], and wound healing pathways," the authors write.
"We believe our findings represent a novel approach to defining clinically relevant cohorts of NSCLC stratified by age and sex that are enriched for specific pathway activity and that would be more apt for therapeutic intervention when planning clinical trials with drugs that target specific pathway-related abnormalities or tumor biology. With genomic assays now being increasingly practical and clinically applicable, with turnaround times of 5 to 7 days, we believe our findings, while hypothesis generating and needing further validation, represent a step forward in defining pathway-driven cohorts of NSCLC that likely explain the age- and sex-specific differences seen in NSCLC," the authors conclude.
(JAMA. 2010;303:535-543. Available pre-embargo to the media at www.jamamedia.org)
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