MicroRNA profiling and prediction of recurrence/relapse-free survival in stage I lung cancer.

About 30% stage I non-small cell lung cancer (NSCLC) patients undergoing resection will recur. Robust prognostic markers are required to better manage therapy options. MicroRNAs (miRNAs) are a class of small non-coding RNAs of 19-25 nt and play important roles in gene regulation in human cancers. The purpose of this study is to identify miRNA expression profiles that would better predict prognosis of stage I NSCLC. MiRNAs extracted from 527 stage I NSCLC patients were profiled on the human miRNA expression profiling v2 panel (Illumina). The expression profiles were analyzed for their association with cancer subtypes, lung cancer brain metastasis and recurrence/relapse free survival (RFS). MiRNA expression patterns between lung adenocarcinoma and squamous cell carcinoma differed significantly with 171 miRNAs, including Let-7 family members and miR-205. Ten miRNAs associated with brain metastasis were identified including miR-145*, which inhibit cell invasion and metastasis. Two miRNA signatures that are highly predictive of RFS were identified. The first contained 34 miRNAs derived from 357 stage I NSCLC patients independent of cancer subtype, whereas the second containing 27 miRNAs was adenocarcinoma specific. Both signatures were validated using formalin-fixed paraffin embedded and/or fresh frozen tissues in independent data set with 170 stage I patients. Our findings have important prognostic or therapeutic implications for the management of stage I lung cancer patients. The identified miRNAs hold great potential as targets for histology-specific treatment or prevention and treatment of recurrent disease.

Summary of presentations from the 46th annual meeting of the American Society of Clinical Oncology (2010): focus on supportive care issues related to lung cancer.

BACKGROUND: Patients with advanced cancer, particularly of the lung, frequently experience deteriorating physical health. Supportive care measures help ensure optimal quality of life during difficult psychologic and social situations. Research in the area of supportive care in patients with cancer should be made a priority. METHODS: This review summarizes the findings from selected supportive care studies presented at the recently concluded 46 annual meeting of the American Society of Clinical Oncology. DISCUSSION: Topics discussed include the use of a single dose of fosaprepitant for prevention of chemotherapy-induced nausea and vomiting, statins to lower the incidence of venous thromboembolic events, fentanyl pectin nasal spray for cancer-related pain, and a closer look at the utilization of complementary and alternative medicine in patients with cancer.

Barriers to enrollment in non-small cell lung cancer therapeutic clinical trials.

INTRODUCTION: Despite recent advances in treatment, lung cancer remains the leading cause of cancer-related mortality in the United States. Therefore, there is a strong need for developing clinical trials in lung cancer therapeutics. Only a small fraction of patients with lung cancer are enrolled in clinical trials. It is critical to understand the barriers to participation in lung cancer clinical trials. METHODS: We reviewed the outpatient charts of consecutive patients with non-small cell lung cancer who presented for initial evaluation or consultation for further therapeutic management to the thoracic medical oncology group at the Alvin J. Siteman Cancer Center between January 1, 2006, and December 31, 2006. Available and appropriate clinical trials specific to the histologic subtype and stage were presented to the patients routinely, and reasons for nonenrollment were documented. We collected information on age, gender, ethnicity, histology, stage, performance status (PS), and insurance status. RESULTS: During the study period, 263 patients with non-small cell lung cancer were identified for the study. After initial screening, 183 patients had clinical trials available, which were appropriate for their diagnosis and stage of disease. One hundred one patients (55.2%) were ineligible for enrollment in a clinical trial. The most common reasons for ineligibility were poor PS (18%), need for emergent radiation (12%), lack of adequate staging information (6%), and comorbid conditions (4.9%). Despite being eligible for participation, 57 patients (31.1%) did not enroll in a clinical trial. Patient refusal accounted for 8.7%. The problems with transportation and distance from the medical center were reasons given for nonparticipation by 7.1%. Eleven patients (6%) did not participate in a clinical trial because of insurance issues. Ultimately, 25 patients (13.7%) were enrolled in a clinical trial. CONCLUSIONS: Poor PS, the need for emergent radiation, and patient refusal were the most common reasons for not participating in a clinical trial.

Use of microRNA expression levels to predict outcomes in resected stage I non-small cell lung cancer.

BACKGROUND: Despite undergoing curative resection, nearly a third of patients with stage I non-small cell lung cancer (NSCLC) die of recurrent disease. There are no reliable clinical or molecular predictors of relapse in patients with resected stage I NSCLC. Identifying patients at risk for relapse after surgical resection is one of the important challenges today. MicroRNAs (miRNAs) regulate hundreds of genes central to maintaining a cancer phenotype. METHODS: In an exploratory study, we determined whether expression of six miRNAs (let-7a, miR-7, miR-21, miR-155, miR-210, and miR-221) previously reported to correlate with invasiveness or outcome in various human malignancies were associated with tumor recurrence in patients with resected stage I NSCLC. We measured expression of these miRNAs in formalin-fixed, paraffin-embedded tissue from both tumor and matched normal lung in a set of 46 patients with surgically resected T1 or T2 stage I NSCLC. RESULTS: Averaged triplicate data showed that tumors which recurred had 0.14-fold lower miR-221 expression than those which did not recur (p = 0.0036). In addition, increased miR-221in tumor tissue when compared with adjacent normal appearing lung in the same patient also correlated with nonrecurrence (p = 0.0011). Parallel measurement of expression of selected downstream target genes regulated by miR-221, specifically, CDKN1B, CDKN1C, paralemmin-2, and CXCL12, showed a near significant (p = 0.0522) down-regulation of CDKN1C in tumors of patients with no recurrent disease, consistent with increased miR-221 activity in the same group. CONCLUSION: If confirmed in prospective studies, miRNA expression in resected NSCLC could potentially identify those at high risk of relapse after surgery.