A group of researchers has identified differences in genetic characteristics associated with age- and sex-specific patterns of increased or decreased recurrence-free survival among non-small-cell lung cancer (NSCLC).
“Despite evidence that clinical and pathologic factors, for example, age, histology, smoking status, and sex, are clinically relevant, little is known regarding the underlying biological differences in lung tumor gene expression among patients with different clinicopathologic characteristics,” the authors write in the February 10 issue of JAMA.
“A deeper understanding of molecular abnormalities at a pathway level may help dissect the complex mechanisms of lung cancer oncogenesis, 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.” Their findings appear in a paper titled “Age- and Sex-Specific Genomic Profiles in Non–Small Cell Lung Cancer.”
William Mostertz, of Duke University, and colleagues examined clinically relevant differences in the underlying biology of NSCLC based on 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 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 five-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 (25% vs. 6%) and tumor necrosis factor (76% vs. 42%) pathways compared with low-risk patients. High-risk patients who were 70 years or older demonstrated increased activation of the wound healing (40% vs. 24%) and invasiveness (64% vs. 20%) pathways compared to low-risk patients.
The researchers also 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 pathways, while high-risk men demonstrated increased activation of the STAT3, tumor necrosis factor, EGFR, and wound-healing pathways,” according to the scientists.
“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 five to seven 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 investigators conclude.