Assessment of Circulating miRNA-17 and miRNA-222 Expression Profiles as Non-Invasive Biomarkers in Egyptian Patients with Non-Small-Cell Lung Cancer.

Background: Lung cancer is one of the main human health threats. Survival of lung cancer patients depends on the timely detection and diagnosis. Among the genetic irregularities that control cancer development and progression, there are microRNAs (miRNAs). This study aimed to assess the plasma level of circulating miRNA-17 and miRNA-222 as non-invasive markers in non-small-cell lung cancer (NSCLC) patients. Patients and methods: A total of 40 patients with NSCLC and 20 healthy controls who were matched in terms of age and sex with the patient group were included in this case-control study.. Estimation of miRNA-17 and miRNA-222 expression profiles in the plasma was done using quantitative real-time PCR (qRT-PCR). The relationship between both markers and their clinicopathological features were also determined. Receiver operating characteristic (ROC) curve analysis was done to evaluate the role of these microRNAs in NSCLC diagnosis and follow-up. Results: MiRNA-17 and miRNA-222 levels were significantly upregulated in NSCLC patients compared with controls (48.32±12.35 vs 1.16±0.19 and 34.53±3.1 vs 1.22±0.14) (P=0.000). Plasma miRNA-17 level was increased, and the miRNA-222 level was decreased across different stages of the disease; however, these differences d were not statistically significant (P=0.4, P=0.5, respectively). The miRNA-17 levels were higher in the lung cancer patients with metastasis , but miRNA-222 levels were lower patients without metastasis. We found no statistically significant difference in this regard(P=0.4 vs P=0.3, respectively). ROC curve analysis showed that the sensi¬tivity and specificity of miRNA-17 were 77.78% and 87.50% , and of miRNA-222 were 50% and 88.89%. Conclusion: MiRNA-17 and miRNA-222 can be considered as non-invasive biomarkers for detection of early lung carcinogenesis and metastasis in patients with NSCLC, hence providing a basis for the development of novel therapeutic approaches.

The effect of non-small cell lung cancer histology on survival as measured by the graded prognostic assessment in patients with brain metastases treated by hypofractionated stereotactic radiotherapy.

BACKGROUND: The purpose of this study was to investigate the impact of histology on survival stratified by the Graded Prognostic Assessment (GPA) for non-small cell lung cancer (NSCLC) in a group of selected patients treated recently. METHODS: A total of 171 NSCLC patients with brain metastases treated by hypofractionated stereotactic radiotherapy with or without whole-brain radiotherapy between 2001 and 2011 were included. The GPA score was calculated for each patient. Tumor histologies were categorized into adenocarcinoma (ADCA) and non-ADCA. Median survival time (MST, in months) was calculated using the Kaplan-Meier method. The log-rank test was used to determine statistical differences. RESULTS: MSTs by histology were: ADCA 15 (n = 92) and non-ADCA 10 (n = 79) (p < 0.001). For all patients, the MSTs by GPA score were: GPA 3.5-4, 24; GPA 2.5-3, 15; GPA 1.5-2, 9 and GPA 0-1, 6 (p < 0.001). The histology of ADCA showed a statistically significant higher MST than non-ADCA for patients with GPA 2.5-4. For GPA 2.5-3, MSTs were: ADCA 18, non-ADCA 10 (p = 0.007); for GPA 3.5-4, MSTs were: ADCA 30, non-ADCA 17 (p = 0.046). For GPA 0-2, MSTs did not differ significantly by histology. For GPA 0-1, MSTs were: ADCA 8, non-ADCA 4 (p = 0.146); GPA 1.5-2, MSTs were: ADCA 10, non-ADCA 8 (p = 0.291). We further found that non-ADCA in upper GPA class (3.5-4) had similar survival with ADCA in lower GPA class (2.5-3) (MSTs were 17 and 18, respectively, p = 0.775). This phenomenon also happened between patients of non-ADCA in upper GPA class (2.5-3) and those of ADCA in lower GPA class (1.5-2) (MSTs were both 10, p = 0.724). CONCLUSIONS: We confirmed that the histology of NSCLC had effect on the GPA in these selected patients treated recently. ADCA showed a statistically significant higher MST than non-ADCA with GPA 2.5-4. The non-ADCA in upper GPA classes (3.5-4 and 2.5-3) had similar survival to ADCA in lower GPA classes (2.5-3 and 1.5-2, respectively). The histology as a new factor should be added to the original GPA for NSCLC.

Assessment of objective responses using volumetric evaluation in advanced thymic malignancies and metastatic non-small cell lung cancer.

INTRODUCTION: Measurement of tumor response by standard response criteria is challenging in thymic malignancies, especially when the pleura is involved, as it often is in stage IV disease. In this study, we aimed to determine the effectiveness of volumetric response evaluation criteria in solid tumors (volumetrics) for evaluating response in patients with thymic malignancies treated on a phase II study of belinostat. METHODS: We evaluated the tumor responses of 25 patients with thymic cancer using computed tomography-based RECIST, World Health Organization (WHO), modified RECIST, and volumetrics. As a control, we assessed 37 patients with non-small cell lung cancer (NSCLC) with RECIST and volumetrics. RESULTS: Agreement analyses in 23 patients with thymic cancer at the time of RECIST-determined progressive disease (PD) compared volumetrics with RECIST, modified RECIST, and WHO criteria. Use of volumetrics was associated with 22% discordance compared with RECIST, 15% versus modified RECIST, and 22% versus WHO criteria. Volumetrics revealed PD 72 days earlier than RECIST (p = 0.016). In another cohort of 35 patients with NSCLC, there was 9% discordance between volumetrics and RECIST at the time of PD. Volumetrics demonstrated PD 32 days earlier than RECIST in NSCLC (p = 0.0078). CONCLUSIONS: Our study suggests that volumetrics might improve detection of PD. Prospective evaluation of this technique in a larger series of patients with thymic malignancies will be required.

Epidemiology and treatment costs of bone metastases from lung cancer: a French prospective, observational, multicenter study (GFPC 0601).

INTRODUCTION: The aim of this prospective, observational, multicenter study was to examine the epidemiology and management costs of bone metastatic disease (BMD) in patients with lung cancer. METHODS: The analysis included all patients with BMD from lung cancer diagnosed between May 2006 and May 2007 in 40 centers. We analyzed their management and the direct costs of BMD from the health care provider's perspective, using a Markov model. Skeletal-related event (SRE) was defined as pathological fractures, spinal cord compression, or hypercalcemia (clinical SRE [cSRE]) for an initial analysis; a second analysis included palliative radiotherapy and surgery (therapeutic SRE [tSRE]). RESULTS: Among the 554 patients enrolled (62 ± 11 years, 76.5% males, 69.3% performance status 0/1, 91% non-small cell lung cancer), 24.7% had a cSRE and 26.7% a tSRE at baseline and 9% and 39% during follow-up, respectively; 81.8% received at least one chemotherapy cycle. The median survival time was 5.8 months, and the 1- and 2-year survival rates were 22% and 7%, respectively; there was no significant difference in overall survival between the patients with and without SRE at enrollment. The main BMD treatments were opiate therapy (77.7%), biphosphonates (52.3%), radiotherapy (42.1%), and surgery (9.2%). The mean monthly BMD treatment costs in euros were €190, €374, and €4672 for asymptomatic patients, symptomatic patients, and patients with SRE, respectively. The average first-year BMD management cost in euros was €3999 ± 4135 (95% confidence interval: 374-15,886), and 49.5% of this cost was attributable to patients with SRE. CONCLUSIONS: This analysis confirms the poor prognosis of BMD from lung cancer and underlines the burden of SRE in overall treatment costs.

Deregulated expression of hnRNP A/B proteins in human non-small cell lung cancer: parallel assessment of protein and mRNA levels in paired tumour/non-tumour tissues.

BACKGROUND: Heterogeneous nuclear ribonucleoproteins (hnRNPs) of the A/B type (hnRNP A1, A2/B1, A3) are highly related multifunctional proteins participating in alternative splicing by antagonising other splicing factors, notably ASF/SF2. The altered expression pattern of hnRNP A2/B1 and/or splicing variant B1 alone in human lung cancer and their potential to serve as molecular markers for early diagnosis remain issues of intense investigation. The main objective of the present study was to use paired tumour/non-tumour biopsies from patients with non-small cell lung cancer (NSCLC) to investigate the expression profiles of hnRNP A1, A2/B1 and A3 in conjunction with ASF/SF2. METHODS: We combined western blotting of tissue homogenates with immunohistochemical examination of fixed tissue sections and quantification of mRNA expression levels in tumour versus adjacent normal-looking areas of the lung in the same patient. RESULTS: Our study, in addition to clear evidence of mostly uncoupled deregulation of hnRNPs A/B, has revealed hnRNP A1 to be the most deregulated protein with a high frequency of over-expression (76%), followed by A3 (52%) and A2/B1 (43%). Moreover, direct comparison of protein/mRNA levels showed a lack of correlation in the case of hnRNP A1 (as well as of ASF/SF2), but not of A2/B1, suggesting that different mechanisms underlie their deregulation. CONCLUSION: Our results provide strong evidence for the up-regulation of hnRNP A/B in NSCLC, and they support the existence of distinct mechanisms responsible for their deregulated expression.