Clinical and Molecular Predictors of Recurrence in Stage I Non-Small Cell Lung Cancer

Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
The Annals of thoracic surgery (Impact Factor: 3.85). 03/2012; 93(5):1606-12. DOI: 10.1016/j.athoracsur.2012.01.048
Source: PubMed


Patients with stage I lung cancer undergoing a complete resection have a 25% risk of recurrence. Factors predictive for recurrence are critically needed. In the present study, we prospectively examined clinical and molecular factors that may predict a poor outcome.
Patients with stage I non-small cell lung cancer undergoing surgical resection were enrolled into an institutional registry. Clinical demographics and outcomes data were prospectively collected. Patients who received neoadjuvant therapy or patients who died within 30 days of surgery were excluded from this analysis. Molecular factors involved in cell proliferation, cell cycle control, apoptosis, and angiogenesis were analyzed. The primary endpoint was recurrence-free survival.
One hundred and two patients were enrolled between March 2006 and April 2009. There were 25 (25%) documented recurrences. In univariate analysis, male sex, increased tumor standard uptake value, tumor size, final pathology stage, arterial invasion, percent nuclear phosphorylated AKT, vascular endothelial growth factor score, negative cyclin D1 protein expression, and percent nuclear cyclin D1 expression were predictive of decreased recurrence-free survival. All factors with a p value of 0.1 or less were included in multivariate analysis. Male sex, final pathology stage, vascular endothelial growth factor score, and percent nuclear cyclin D1 expression were significant independent predictors for poor prognosis.
Four clinical and molecular factors were associated with prognosis in a prospective study of stage I non-small cell lung cancer.

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    • "Using p-p70S6K enabled us to identify a subset of patients with LG-URCa who had an increased risk for recurrence. These results were similar to those of our previous study in a non-muscle invasive bladder cancer cohort, in which the high expression of p-p70S6K was a predictive factor for recurrence of early breast cancer and lung cancer.81314 Sun et al.,15 reported that high expression of p-S6, a substrate of p-p70S6K, predicts the progression of non-muscle-invasive URCa of the bladder treated by transurethral resection in immunohistochemical staining of 266 human UC samples, and that the unfavorable prognostic findings of p-p70S6K overexpression have been reported in other solid tumors.1316 "
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    ABSTRACT: We investigated whether inhibiting phosphorylated p70S6K (p-p70S6K) suppresses the proliferation and growth of noninvasive low-grade urothelial carcinoma (LG-URCa) in vitroand whether p-p70S6K can serve as a predictive biomarker for the recurrence of noninvasive LG-URCa of the bladder in patients. We constructed a tissue microarray (TMA) for 95 LG-URCa and 35 benign urothelium samples and performed immunohistochemical staining for p-p70S6K and p-4E-BP1. A Cox regression model was used to investigate the predictive factors for recurrence of LG-URCa. We investigated the dose-dependent antiproliferative effect of rapamycin, its antiproliferative effect and the growth-inhibition effect of p70S6K siRNA transfection in RT4 and 253J cell lines. The pT1 staged group (P < 0.05; hazard ratio (HR), 2.415) and the high p-p70S6K staining group (P < 0.05; HR, 2.249) were independent factors for predicting recurrence. Rapamycin inhibited RT4 and 253J cell proliferation in a dose-dependent manner (r = -0.850, P< 0.001 in RT4 cells; r = -0.835, P< 0.001 in 253J cells). RT4 and 253J cell proliferation and growth were inhibited by the transfection of p70S6K siRNA and rapamycin, respectively (P < 0.05). Transfection of p70S6K siRNA resulted in inhibitory effects on cell proliferation and growth that were similar to those of rapamycin. Our results suggest that inhibiting p70S6K phosphorylation is important to prevent recurrence and that p70S6K phosphorylation can be used as a molecular biomarker to predict recurrence of certain LG-URCa of the bladder.
    Asian Journal of Andrology 03/2014; 16(4). DOI:10.4103/1008-682X.123675 · 2.60 Impact Factor

  • The Annals of thoracic surgery 05/2012; 93(5):1613. DOI:10.1016/j.athoracsur.2012.02.057 · 3.85 Impact Factor
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    ABSTRACT: Objectives: To examine the relationship between preoperative serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (I-CTP) levels and postoperative distant metastasis in patients with non-small-cell lung cancer (NSCLC). Methods: We retrospectively reviewed 143 patients in whom preoperative serum I-CTP level was measured from January 2006 to March 2011, including 91 males and 52 females with an average age of 70.1 ± 8.2 years. Histological subtypes included adenocarcinoma (n = 95), squamous cell carcinoma (n = 34) and other (n = 14). Preoperative serum carcinoembryonic antigen (CEA) and cytokeratin-19 fragment (CYFRA) levels were also measured. Patients with abnormal renal function or preoperative bone fractures were excluded. Results: The mean preoperative serum I-CTP level was 4.1 ± 1.6 ng/ml, and the preoperative serum I-CTP level was elevated (>4.5 ng/ml) in 29 patients. Distant metastasis was detected in 21 patients during the 39 ± 18 (range 1-79) months of follow-up. The rate of distant metastasis was significantly higher in patients with elevated preoperative serum I-CTP levels than those with normal preoperative I-CTP levels (≤4.5 ng/ml) (P < 0.0001). The 5-year recurrence-free survival rate was lower in patients with elevated preoperative serum I-CTP levels than those with normal preoperative I-CTP levels (41.8 vs 92.9%; P < 0.0001). Conclusions: An elevated preoperative serum I-CTP level predicts postoperative distant metastasis in patients with NSCLC.
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