Discriminating association of a common telomerase reverse transcriptase promoter polymorphism with telomere parameters in non-small cell lung cancer with or without epidermal growth factor receptor mutation.

BACKGROUND: The role of epidermal growth factor receptor (EGFR) pathways in regulating telomerase is increasingly being recognised. We analysed the impact of rs2853669 single nucleotide polymorphism (SNP) on telomere parameters and its prognostic value for non-small cell lung cancer (NSCLC) with or without EGFR mutation. METHODS: The association of rs2853669 with telomerase reverse transcriptase (TERT) mRNA level and relative telomere length (RTL) was analysed using resected tumour samples from 250 NSCLC patients. We also investigated the patients' clinical outcomes with a median follow-up of 57 months (2-99 months). RESULTS: The rs2853669 T/C allele was significantly associated with lower TERT mRNA expression (versus C/C and versus T/T; p < 0.001 for both) and shorter RTL (versus C/C and versus T/T; p = 0.039 and 0.023) in patients without EGFR mutation. Such difference was not observed in their counterparts harbouring EGFR mutation. When considering the cohort as a whole, T/C allele was significantly associated with shortest overall survival compared with T/T or C/C allele (mean: 61.8, 80.9 and 88.7 months, plog-rank < 0.001) and disease-free survival (mean: 78.3, 87.9 and 91.5 months, plog-rank = 0.019). Stratification analyses showed that the negative prognostic effect of T/C on OS was constrained in patients without EGFR mutation. CONCLUSION: Our study revealed significant associations of a common SNP within TERT promoter region on telomere parameters and survival in NSCLC patients without EGFR mutation. The result may help providing instruction for therapeutic interventions targeting telomerase and evidence for investigation of TERT-EGFR interacting mechanism in telomere biology.

Sublobar Resection for Pulmonary Aspergilloma: A Safe Alternative to Lobectomy.

BACKGROUND: This study was performed to evaluate the effectiveness of sublobar resection for the treatment of pulmonary aspergilloma compared with lobectomy. METHODS: Patients with pulmonary aspergilloma who underwent lobectomy or sublobar resection in our department between March 2007 and December 2015 were retrospectively reviewed. Data were collected for patient demographic characteristics, medical history, preoperative investigations, perioperative findings, postoperative conditions, and recurrence status. Propensity-matched comparative analyses were performed to adjust for potential differences of patients' baseline characteristics between the groups. RESULTS: A total of 96 patients underwent lobectomy, 46 patients underwent attempted sublobar resection. The median follow-up time is 53 months. No recurrence was found in either group. Three patients (3.1%) in the lobectomy group required reoperation for bleeding. The patients who underwent sublobar resection had less underlying lung disease (p = 0.031), smaller lesions (p = 0.033), and were more likely to have been treated with video-assisted thoracic surgery (p < 0.001). These differences were eliminated by propensity score matching (46 pairs were successfully matched). Comparative analyses in matched groups demonstrate that there was no marked difference in the volume and duration of chest drainage or the length of postoperative hospital stay. However, the patients with sublobar resection had shorter operation time (p = 0.004), less blood loss (p = 0.042), and less postoperative complication (p = 0.048). CONCLUSIONS: Sublobar resection performed for small simple pulmonary aspergilloma and selected complex pulmonary aspergilloma has a low recurrence rate and confers perioperative advantages compared with lobectomy.

Clinical, cellular, and bioinformatic analyses reveal involvement of WRAP53 overexpression in carcinogenesis of lung adenocarcinoma.

Lung cancer, of which non-small cell lung cancer accounts for 80%, remains a leading cause of cancer-related mortality and morbidity worldwide. Our study revealed that the expression of WD repeat containing antisense to P53 (WRAP53) is higher in lung-adenocarcinoma specimens than in specimens from adjacent non-tumor tissues. The prevalence of WRAP53 overexpression was significantly higher in patients with tumor larger than 3.0 cm than in patients with tumor smaller than 3.0 cm. The depletion of WRAP53 inhibits the proliferation of lung-adenocarcinoma A549 and SPC-A-1 cells via G1/S cell-cycle arrest. Several proteins interacting with WRAP53 were identified through co-immunoprecipitation and liquid chromatography/mass spectrometry. These key proteins indicated previously undiscovered functions of WRAP53. These observations strongly suggested that WRAP53 should be considered a promising target in the prevention or treatment of lung adenocarcinoma.

Downregulation of RUVBL1 inhibits proliferation of lung adenocarcinoma cells by G1/S phase cell cycle arrest via multiple mechanisms.

Lung cancer remains a leading cause of cancer-related mortality and morbidity worldwide, of which non-small cell lung cancer (NSCLC) accounts for 80 %. RUVBL1 is a highly conserved eukaryotic AAA+ adenosine 5'-triphosphatase (ATPase) that has many functions highly relevant to cancer. We therefore attempted to determine the potential role of RUVBL1 in the biogenesis of lung adenocarcinoma and obtained some interesting results. Our study revealed that RUVBL1 expression was higher in lung adenocarcinoma specimens than in those of adjacent non-tumor tissues and in lung cancer cell lines than in normal lung cell lines. RUVBL1 knockdown via siRNA reduced proliferation and caused G1/S phase cell cycle arrest in lung adenocarcinoma cell lines. The G1/S phase cell cycle arrest triggered by RUVBL1 downregulation could be attributed, at least in part, to repression of the AKT/GSK-3ß/cyclin D1 pathway and probably to the activation of IRE1α-mediated endoplasmic reticulum (ER) stress. We thus demonstrated for the first time that a knockdown of RUVBL1 could effectively inhibit the proliferation of lung adenocarcinoma A549 and H292 cells through the induction of G1/S phase cell cycle arrest via multiple mechanisms. These observations strongly suggested that RUVBL1 should be considered a promising target for the prevention or therapy of lung adenocarcinoma.

Time-to-Progression of NSCLC from Early to Advanced Stages: An Analysis of data from SEER Registry and a Single Institute.

The average time required for cancers to progress through stages can be reflected in the average age of the patients diagnosed at each stage of disease. To estimate the time it takes for non-small-cell lung cancer (NSCLC) to progress through different tumor, node and metastasis (TNM) stages and sizes, we compared the mean adjusted age of 45904 NSCLC patients with different stages and tumor sizes from Surveillance, Epidemiology and End Results (SEER) cancer registry database and our institute. Multiple-linear-regression models for age were generated adjusting for various factors. Caucasian, African-American and Asian patients with stage IA cancers were on average 0.8, 1.0 and 1.38 adjusted years younger, respectively, than those with stage IIIB cancers (p < 0.001). And these with T1a cancers were on average 0.84, 0.92 and 1.21 adjusted years younger, respectively, than patients with T3 cancers (p < 0.001). Patients with tumors measuring larger than 8 cm in diameter were on average 0.85 adjusted years older than these with tumors smaller than 1 cm (p < 0.001), with Caucasian demonstrating the shortest age span (0.79 years, P < 0.001). In conclusion, the time-to-progression of NSCLC from early to advanced stages varied among ethnicities, Caucasian patients demonstrating a more rapid progression nature of tumor than their African-American and Asian counterparts.

ECMO-assisted esophagectomy after left pneumonectomy.

BACKGROUND: Esophagectomy after pneumonectomy has been rarely reported, mainly due to the technical difficulty in performing this surgical approach. Conventional intubation to the contralateral respiratory passage is technically challenging, while the homolateral respiratory tract is absent, making oxygenation impossible. METHODS: To overcome this problem, we used venoarterial (VA) extracorporeal membrane oxygenation (ECMO) which can help achieve gas exchange despite the collapsed lung and provide a clear unobstructed surgical field for esophagectomy. RESULTS: We obtained satisfactory outcomes with VA ECMO in our treated patient. CONCLUSIONS: This technique may be an excellent option for the treatment of complex situations such as esophagectomy after pneumonectomy.