Long non-coding RNAs (lncRNAs) govern fundamental biochemical and cellular processes. lncRNA HOX transcript antisense RNA (HOTAIR) represses gene expression through recruitment of chromatin modifiers. The expression of HOTAIR is elevated in lung cancer and correlates with metastasis and poor prognosis. Moreover, HOTAIR promotes proliferation, survival, invasion, metastasis, and drug resistance in lung cancer cells. Here we review the molecular mechanisms underlying HOTAIR-mediated aggressive phenotypes of lung cancer. We also discuss HOTAIR’s potential in diagnosis and treatment of lung cancer, as well as the challenges of exploiting HOTAIR for intervention of lung cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-014-0090-4) contains supplementary material, which is available to authorized users.
Background
Identifying strong markers of prognosis is critical to optimize treatment and survival outcomes in patients with non-small cell lung cancer (NSCLC). We investigated the prognostic significance of preoperative cardiorespiratory fitness (VO2peak) among operable candidates with NSCLC.
Methods
Using a prospective design, 398 patients with potentially resectable NSCLC enrolled in Cancer and Leukemia Group B (CALGB) 9238 were recruited between 1993 and 1998. Participants performed a cardiopulmonary exercise test to assess VO2peak and were observed for death or until June 2008. Cox proportional models were used to estimate the risk of all-cause mortality according to cardiorespiratory fitness category defined by VO2peak tertiles (<0.96 / 0.96–1.29 / >1.29 L.min−1) with adjustment for age, gender, performance status.
Results
Median follow-up was 30.8 months, 294 deaths were reported during this period. Compared with patients achieving a VO2peak <0.96 L.min−1, the adjusted hazard ratio (HR) for all-cause mortality was 0.64 (95% CI, 0.46 to 0.88) for a VO2peak of 0.96–1.29 L.min−1, and 0.56 (95% CI, 0.39 to 0.80) for a VO2peak of >1.29 L.min−1 (ptrend= 0.0037). The corresponding HRs for resected patients were 0.66 (95% CI, 0.46 to 0.95) and 0.59 (95% CI, 0.40 to 0.89) relative to the lowest VO2peak category (ptrend=0.0247), respectively. For non-resected patients, the HRs were 0.78 (95% CI, 0.34 to 1.79) and 0.39 (95% CI, 0.16 to 0.94) relative to the lowest category (ptrend=0.0278).
Conclusions
VO2peak is a strong independent predictor of survival in NSCLC that may complement traditional markers of prognosis to improve risk stratification and prognostication.
Our data provide multicenter validation for the use of exercise Vo2 for preoperative assessment of lung cancer patients, and we encourage an aggressive approach when evaluating these patients for surgery.
Objectives
The primary objective of this study was to evaluate the benefit of using a new fluorescence-reflectance imaging system, Onco-LIFE, for the detection and localization of intraepitheal neoplasia and early invasive squamous cell carcinoma. A secondary objective was to evaluate the potential use of quantitative image analysis with this device for objective classification of abnormal sites.
Design
This study was a prospective, multicenter, comparative, single arm trial. Subjects for this study were aged 45 to 75 years and either current or past smokers of more than 20 pack-years with airflow obstruction, forced expiratory volume in 1 second/forced vital capacity less than 75%, suspected to have lung cancer based on either sputum atypia, abnormal chest roentgenogram/chest computed tomography, or patients with previous curatively treated lung or head and neck cancer within 2 years.
Materials and Methods
The primary endpoint of the study was to determine the relative sensitivity of white light bronchoscopy (WLB) plus autofluorescence-reflectance bronchoscopy compared with WLB alone. Bronchoscopy with Onco-LIFE was carried out in two stages. The first stage was performed under white light and mucosal lesions were visually classified. Mucosal lesions were classified using the same scheme in the second stage when viewed with Onco-LIFE in the fluorescence-reflectance mode. All regions classified as suspicious for moderate dysplasia or worse were biopsied, plus at least one nonsuspicious region for control. Specimens were evaluated by the site pathologist and then sent to a reference pathologist, each blinded to the endoscopic findings. Positive lesions were defined as those with moderate/severe dysplasia, carcinoma in situ (CIS), or invasive carcinoma. A positive patient was defined as having at least one lesion of moderate/severe dysplasia, CIS, or invasive carcinoma. Onco-LIFE was also used to quantify the fluorescence-reflectance response (based on the proportion of reflected red light to green fluorescence) for each suspected lesion before biopsy.
Results
There were 115 men and 55 women with median age of 62 years. Seven hundred seventy-six biopsy specimens were included. Seventy-six were classified as positive (moderate dysplasia or worse) by pathology. The relative sensitivity on a per-lesion basis of WLB + FLB versus WLB was 1.50 (95% confidence interval [CI], 1.26–1.89). The relative sensitivity on a per-patient basis was 1.33 (95% CI, 1.13–1.70). The relative sensitivity to detect intraepithelial neoplasia (moderate/severe dysplasia or CIS) was 4.29 (95% CI, 2.00–16.00) and 3.50 (95% CI, 1.63–12.00) on a per-lesion and per-patient basis, respectively. For a quantified fluorescence reflectance response value of more than or equal to 0.40, a sensitivity and specificity of 51% and 80%, respectively, could be achieved for detection of moderate/severe dsyplasia, CIS, and microinvasive cancer.
Conclusions
Using autofluorescence-reflectance bronchoscopy as an adjunct to WLB with the Onco-LIFE system im...
Background: Although a large number of epidemiological studies have examined the role of aspirin in the chemoprevention of colon cancer and other solid tumors, there is a limited body of research focusing on the association between aspirin and lung cancer risk.
Background: Because cells progressing to cancer must proliferate, marker proteins specific to proliferating cells may permit detection of premalignant lesions. Here we compared the sensitivities of a classic proliferation marker, Ki-67, with a new proliferation marker, MCM2, in 41 bronchial biopsy specimens representing normal mucosa, metaplasia, dysplasia, and carcinoma in situ.
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