Clinical predictors of severe radiation pneumonitis in patients undergoing thoracic radiotherapy for lung cancer.

Background: Severe radiation pneumonitis (RP), one of adverse events in patients with lung cancer receiving thoracic radiotherapy, is more likely to lead to more mortality and poor quality of life, which could be predicted by clinical information and treatment scheme. In this study, we aimed to explore the clinical predict model for severe RP. Methods: We collected information on lung cancer patients who received radiotherapy from August 2020 to August 2022. Clinical features were obtained from 690 patients, including baseline and treatment data as well as radiation dose measurement parameters, including lung volume exceeding 5 Gy (V5), lung volume exceeding 20 Gy (V20), lung volume exceeding 30 Gy (V30), mean lung dose (MLD), etc. Among them, 621 patients were in the training cohort, and 69 patients were in the test cohort. Three models were built using different screening methods, including multivariate logistics regression (MLR), backward stepwise regression (BSR), and random forest regression (RFR), to evaluate their predictive power. Overoptimism in the training cohorts was evaluated by four validation methods, including hold-out, 10-fold, leave-one-out, and bootstrap methods, and test cohort was used to evaluate the predictive performance of the model. Model calibration, decision curve analysis (DCA), and evaluation of the nomograms for the three models were completed. Results: Severe RP was up to 9.4%. The results of multivariate analysis of logistics regression in all patients showed that patients with subclinical (untreated and asymptomatic) interstitial lung disease (ILD) could increase the risk of severe RP, and patients with a better lung diffusion function and received standardized steroids treatment could decrease the risk of severe RP. The three models built by MLR, BSR, and RFR all had good accuracy (>0.850) and moderate κ value (>0.4), and the model 2 built by BSR had the highest area under the receiver operating characteristic (ROC) curve (AUC) in three models, which was 0.958 [95% confidence interval (CI): 0.932-0.985]. The calibration curve showed good agreement between the predicted and actual values, and the DCA showed a positive net benefit for the model 2 which drew the nomogram. The model 2 included subclinical ILD, diffusing capacity of the lung for carbon monoxide (DLCO), ipsilateral lung V20, and standardized steroid treatment, which could affect the incidence of severe RP. Conclusions: Subclinical ILD, DLCO, ipsilateral lung V20, and with or not standardized steroid treatment could affect the incidence of severe RP. Strict lung dose limitation and standardized steroid treatment could contribute to a decrease in severe RP.

Prognostic value of the peripheral blood lymphocyte/monocyte ratio combined with 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma.

OBJECTIVE: To explore the prognostic value of the peripheral blood lymphocyte/monocyte ratio (LMR) combined with 18F-FDG PET/CT for diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical data of 203 patients with primary DLBCL who were hospitalized to the First People's Hospital of Lianyungang between January 2017 and December 2022 were retrospectively analyzed. Before and after three courses of treatment, PET/CT was performed on forty DLBCL patients. The subject operating characteristic (ROC) curve has been employed to determine the most effective LMR cutoff points. According to the criteria for assessing the efficacy of Lugano lymphoma, the PET/CT findings after 3 courses of treatment were specified as complete remission (CR), partial remission (PR), stable disease (SD) and disease progression (PD). The CR group, PR+SD group, and PD group were the three groups created from the four outcomes. Results were analyzed using the Cox proportional risk model, the Kaplan-Meier method (K-M), and the log-rank test. RESULTS: An optimal cutoff point of 3.00 for the LMR in 203 patients was determined by the SPSS 26 software ROC curve. When LMR≥3.00, the 1-year, 3-year, and 5-year OS (Overall Survival) rates are 98%, 88%, and 64% respectively, and the PFS (Progression-free Survival) rates are 90%, 75%, and 56% respectively. When LMR <3.00, the 1-year, 3-year, and 5-year OS rates are 96%, 72%, and 28% respectively, and the PFS rates are 83%, 60%, and 28% respectively. A lower LMR was substantially related with shorter OS, and PFS, according to a K-M survival analysis (P<0.005). LMR<3.00 was an independent predictor of OS, based on a multifactorial Cox analysis (P=0.037). K-M survival analysis of the 18F-FDG PET/CT results of 40 patients revealed that both OS and PFS were statistically significant (P<0.001). Patients were separated into 3 groups combining LMR and 18F-FDG PET/CT: PET/CT CR patients with LMR≥3.00, PET/CT PD patients with LMR<3.00, and others. The Kaplan-Meier analysis revealed that there were significant differences in OS and PFS for each of the three groups (P<0.001). ROC curves showed that the area under the curve (AUC) of the combined testing of the two was 0.735, and the combined testing of the two was better compared to testing alone (PET/CT AUC=0.535, LMR AUC=0.567). This indicates that combining both PET/CT and LMR is a favorable prediction for DLBCL. CONCLUSION: A decreased LMR at initial diagnosis suggests an unfavorable prognosis for DLBCL patients; For patients with DLBCL, combining 18F-FDG PET/CT and the LMR has a better predictive value.

The efficacy and safety of Zengxiao Jiandu decoction combined with definitive concurrent chemoradiotherapy for unresectable locally advanced non-small cell lung cancer: a randomized, double-blind, placebo-controlled clinical trial.

Background: Traditional Chinese medicine (TCM) makes a synergistic and attenuative effect when combined with chemoradiotherapy. However, strong evidence-based studies are lacking. The study sought to investigate whether Zengxiao Jiandu decoction as an adjunctive therapy is superior to definitive concurrent chemoradiotherapy (DCCRT) alone in unresectable, locally advanced (LA), stage III non-small cell lung cancer (NSCLC). Methods: Patients with unresectable LA-NSCLC were randomly assigned to receive DCCRT either combined with Zengxiao Jiandu decoction (TCM arm) or placebo therapy (Control arm), by computer-generated random assignment lists using a central randomization system. The patients were routinely followed-up every 3 months for the first 2 years after the therapy, and every 6 months for the subsequent 3 years, or earlier if clinically indicated. The primary endpoint was grade ≥3 chemoradiotherapy-related toxicities, while secondary endpoints included the completion rate of chemoradiotherapy, the clinical objective response rate (ORR), and survival. The placebo achieved full consistency in color, aroma, taste and appearance with the Zengxiao Jiandu decoction. Results: From February 2019 to December 2020, 163 patients were randomly allocated to TCM arm (n=82) or Control arm (n=81). Fifty-nine (72.0%) patients in TCM arm finished chemoradiotherapy per protocol and 79 (96.3%) received protocol-specified Zengxiao Jiandu decoction. Forty-two patients in Control arm finished chemoradiotherapy per protocol. The incidence of grade ≥3 chemoradiotherapy-related toxicities was higher in Control arm than TCM arm (44.4% vs. 31.7%, P=0.094). Grade ≥3 radiation pneumonitis occurred more frequently in Control arm than TCM arm (13.6% vs. 3.7%, P=0.024). The completion rate of the protocol-specified chemotherapy was significantly higher in TCM arm than Control arm (79.3% vs. 64.2%, P=0.033), but the completion rates of the definitive-dose radiotherapy were similar. There were no significant differences in ORR between the 2 arms. The progression-free survival (PFS) of TCM arm was significantly better than Control arm (median PFS, 12.0 vs. 9.0 months, P=0.035). However, Zengxiao Jiandu decoction was not found to produce any significant benefit in overall survival. Conclusions: The Zengxiao Jiandu decoction adjunctive therapy, as compared to DCCRT alone, reduced grade ≥3 radiation pneumonitis, improved the completion rate of DCCRT, and prolonged PFS for unresectable LA-NSCLC. Trial Registration: Chinese Clinical Trial Registry ChiCTR2000031667.

High Expression of PDE8B and DUOX2 Associated with Ability of Metastasis in Thyroid Carcinoma.

BACKGROUND: Hormone is an independent factor that induces differentiation of thyroid cancer (TC) cells. The thyroid-stimulating hormone (TSH) could promote the progression and invasion in TC cells. However, few genes related to hormone changes are studied in poorly differentiated metastatic TC. This study is aimed at constructing a gene set's coexpression correlation network and verifying the changes of some hub genes involved in regulating hormone levels. METHODS: Microarray datasets of TC samples were obtained from public Gene Expression Omnibus (GEO) databases. R software and bioinformatics packages were utilized to identify the differentially expressed genes (DEGs), important gene module eigengenes, and hub genes. Subsequently, the Gene Ontology (GO) enrichment analysis was constructed to explore important biological processes that are associated with the mechanism of poorly differentiated TC. Finally, some hub gene expressions were validated through real-time PCR and immunoblotting. RESULTS: Gene chip with category number GSE76039 was analyzed, and 1190 DEGs were screened with criteria of P < 0.05 and ∣log2foldchange | >2. Our analysis showed that human dual oxidase 2 (DUOX2) and phosphodiesterase 8B (PDE8B) are the two important hub genes in a coexpression network. In addition, the validated experimental results showed that the expression levels of both DUOX2 and PDE8B were elevated in poorly differentiated metastatic TC tissues. CONCLUSION: This study identified and validated that DUOX2 and PDE8B were significantly associated with the metastasis ability of thyroid carcinoma.

A propensity-matched analysis of stereotactic body radiotherapy and sublobar resection for stage I non-small cell lung cancer in patients at high risk for lobectomy: the results in a Chinese population.

BACKGROUND: To investigate the comparative effectiveness of stereotactic body radiotherapy (SBRT) and sublobar resection (SLR) in patients with stage I non-small cell lung cancer (NSCLC) considered to be high-risk lobectomy patients. METHODS: From January 2012 to December 2015, patients who underwent SBRT or SLR for clinical stage I NSCLC were examined retrospectively. Propensity score matching (PSM) was performed to reduce selection bias in SBRT and SLR patients. RESULTS: Data from 86 SBRT and 79 SLR patients was collected. Median follow-up periods of the SBRT and SLR groups were 32 and 37 months, respectively. Patients treated with SBRT exhibited significantly higher age, higher likelihood of being male, larger tumor diameter, lower forced expiratory volume in 1 second (FEV1), and poorer performance status compared with SLR patients. There were no significant differences between SBRT and SLR patients for 3-year overall survival (OS) (80.3% and 82.3%, P=0.405), cause-specific survival (CSS) (81.3% and 83.4%, P=0.383), and local control (LC) (89.7% and 86.0%, P=0.501). Forty-nine patients were identified from each group after performing PSM. After patients were matched for age, gender, performance status, tumor characteristics and pulmonary function, no significant differences were observed in 3-year OS (85.4% and 73.3%, P=0.649), CSS (87.2% and 74.9%, P=0.637) and LC (95.6% and 82.1%, P=0.055). Prevalence of significant adverse events (grade 3 or worse) was 0% and 10.2% in the matched SBRT and SLR groups (P=0.056), respectively. CONCLUSIONS: Disease control and survival in the SBRT patients was equivalent to that seen in SLR patients with stage I NSCLC considered high-risk lobectomy candidates. SBRT could therefore be an alternative option to SLR in treating patients with a high operative risk.

A nomogram for predicting the risk of lymph node metastasis in T1-2 non-small-cell lung cancer based on PET/CT and clinical characteristics.

BACKGROUND: Accurately predicting the risk level for a lymph node metastasis is critical in the treatment of non-small cell lung cancer (NSCLC). This study aimed to construct a novel nomogram to identify patients with a risk of lymph node metastasis in T1-2 NSCLC based on positron emission tomography/computed tomography (PET/CT) and clinical characteristics. METHODS: From January 2011 to November 2017, the records of 318 consecutive patients who had undergone PET/CT examination within 30 days before surgical resection for clinical T1-2 NSCLC were retrospectively reviewed. A nomogram to predict the risk of lymph node metastasis was constructed. The model was confirmed using bootstrap resampling, and an independent validation cohort contained 156 patients from June 2017 to February 2020 at another institution. RESULTS: Six factors [age, tumor location, histology, the lymph node maximum standardized uptake value (SUVmax), the tumor SUVmax and the carcinoembryonic antigen (CEA) value] were identified and entered into the nomogram. The nomogram developed based on the analysis showed robust discrimination, with an area under the receiver operating characteristic curve of 0.858 in the primary cohort and 0.749 in the validation cohort. The calibration curve for the probability of lymph node metastasis showed excellent concordance between the predicted and actual results. Decision curve analysis suggested that the nomogram was clinically useful. CONCLUSIONS: We set up and validated a novel and effective nomogram that can predict the risk of lymph node metastasis for individual patients with T1-2 NSCLC. This model may help clinicians to make treatment recommendations for individuals.

Four-year follow-up outcomes after stereotactic body radiation therapy for central early-stage non-small cell lung cancer.

BACKGROUND: Previous research has shown that stereotactic body radiation therapy (SBRT) can achieve a high level of tumor control in patients with early-stage non-small cell lung cancer (NSCLC). However, to date, such studies have mainly focused on peripheral early-stage patients. This study aimed to assess the clinical outcomes and toxicity of patients with central lung cancer treated with SBRT in our institution. METHODS: A total of 31 consecutive central early-stage NSCLC patients who were treated with SBRT using the biologically effective dose (BED; α/ß =10) 100-119 Gy in 4-10 fractions between April, 2013, and August, 2016, were reviewed. The RTOG 0813 trial standard was used to define whether the NSCLC was centrally located. All patients received four-dimensional computed tomography (4D CT) simulation. Intensity modulated radiation therapy (IMRT) and three-dimensional conformal radiation therapy (3D CRT) techniques were used in treatment planning. The dose to the planning target volume (PTV) was prescribed to the 95% isodose line. Mainly dosimetric parameters, clinical outcomes, and toxicity were analyzed. RESULTS: The 31 patients enrolled in the study had a median follow-up time of 47.7 months, and the median tumor diameter was 2.2 cm (range, 1.3-5.0 cm). A total of 15 patients (48.4%) developed disease recurrence. The incidences of local, regional, and distant disease recurrence at 3 years were 11.7%, 9.7%, and 30.7%, respectively; at 5 years, they were 21.5%, 15.0%, and 35.0%, respectively. The 3- and 5-year progression-free survival (PFS) rates were 55.1% and 40.5%, respectively; the corresponding overall survival (OS) rates were 85.3% and 68.4%, respectively. Toxicities of grade 3 or higher were observed in 6.5% of the patients. None of the patients experienced grade 4 or 5 acute adverse events; however, 2 patients possibly died of treatment-related late toxicity. CONCLUSIONS: SBRT with a BED 100 Gy in 4-10 fractions is effective and acceptable for treating patients with central early-stage NSCLC. Further studies are warranted.

Downregulation of HSPA2 inhibits proliferation via ERK1/2 pathway and endoplasmic reticular stress in lung adenocarcinoma.

BACKGROUND: To explore the mechanisms of HSPA2 downregulation in inhibiting the proliferation of lung adenocarcinoma. METHODS: We obtained 85 specimens of human lung adenocarcinoma and specimens of adjacent nontumor tissues from the First Affiliated Hospital, School of Medicine, Zhejiang University. We then analyzed the expression of HSPA2 in these tissues and in lung adenocarcinoma and normal lung cell lines. Human lung adenocarcinoma cell lines were transfected with siRNA silencing HSPA2 and subjected to colony forming, Thiazolyl blue tetrazolium bromide (MTT), propidium iodide flow cytometry, immunofluorescence assay and western blotting to explore the causes of the reduction in the proliferation of lung adenocarcinoma cells and the endoplasmic reticulum stress induced by HSPA2 downregulation. Finally, we confirmed these mechanisms via rescue assay. RESULTS: Greater HSPA2 expression was found in the lung adenocarcinoma specimens than in the specimens of adjacent nontumor tissues, and greater expression was found in lung adenocarcinoma cell lines than in normal cell lines. HSPA2 knockdown via siRNA reduced proliferation and led to G1/S phase cell cycle arrest in the lung adenocarcinoma cell lines. G1/S phase cell cycle arrest triggered by HSPA2 downregulation could be attributed, at least in part, to phosphorylation and activation of the Erk1/2 pathway and probably to activation of IRE1α/PERK-mediated endoplasmic reticulum stress. CONCLUSIONS: HSPA2 plays an important role in the origin and development of lung adenocarcinoma. It is thus deserving of further study as a promising clinical therapeutic target.

Survival Rates After Lobectomy, Segmentectomy, and Wedge Resection for Non-Small Cell Lung Cancer.

BACKGROUND: This study aimed to compare the survival rates after lobectomy, segmentectomy, and wedge resection for the eighth edition of the tumor, node, metastasis classification for stage IA non-small cell lung cancer (NSCLC). METHODS: Patients who underwent lobectomy, segmentectomy, or wedge resection for stage IA NSCLC were identified from the Surveillance, Epidemiology, and End Results database. A Cox regression model and propensity-matched analysis were used. The overall survival (OS) rates and lung cancer-specific survival (LCSS) rates among the three groups were compared by tumor size. RESULTS: A total of 16,819 patients met our criteria. Although the OS rate was better for lobectomy than for wedge resection, no statistical differences in the LCSS rate were identified among the three treatment groups of patients with tumors that were 1.0 cm or smaller. For tumors from 1.1 to 2.0 cm, lobectomy and segmentectomy showed no statistical differences in the LCSS rate, but both conferred better OS and LCSS rates than wedge resection. For tumors from 2.1 to 3.0 cm, the OS and LCSS rates were better for lobectomy than for segmentectomy or wedge resection, but similar for segmentectomy and wedge resection. CONCLUSIONS: Lobectomy, segmentectomy, and wedge resection are comparable oncologic procedures for patients with stage IA NSCLC that is 1.0 cm or smaller. For tumors from 1.1 to 2.0 cm, lobectomy and segmentectomy could lead to equivalent survival rates but showed better survival rates than that observed with wedge resection. For tumors from 2.1 to 3.0 cm, lobectomy is still the standard surgical procedure; for patients who are unsuitable candidates for lobectomy, segmentectomy and wedge resection show similar survival rates.

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.

Clinical Nomogram for Predicting Survival of Esophageal Cancer Patients after Esophagectomy.

The aim of this study was to construct an effective clinical nomogram for predicting the survival of esophageal cancer patients after esophagectomy. We identified esophageal cancer patients (n = 4,281) who underwent esophagectomy between 1988 and 2007 from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database. Clinically significant parameters for survival were used to construct a nomogram based on Cox regression analyses. The model was validated using bootstrap resampling and a Chinese cohort (n = 145). A total of 4,109 patients from the SEER database were included for analysis. The multivariate analyses showed that the factors of age, race, histology, tumor site, tumor size, grade and depth of invasion, and the numbers of metastases and retrieved nodes were independent prognostic factors. All of these factors were selected into the nomogram. The nomogram showed a clear prognostic superiority over the seventh AJCC-TNM classification (C-index: SEER cohort, 0.716 vs 0.693, respectively; P < 0.01; Chinese cohort, 0.699 vs 0.680, respectively; P < 0.01). Calibration of the nomogram predicted the probabilities of 3- and 5-year survival, which corresponded closely with the actual survival rates. This novel prognostic model may improve clinicians' abilities to predict individualized survival and to make treatment recommendations.

Log Odds of Positive Lymph Nodes Predicts Survival in Patients After Resection for Esophageal Cancer.

BACKGROUND: The number of lymph node metastases (LNMs) and the positive lymph node ratio (LNR) have been shown to be significant independent prognostic factors in predicting overall survival in patients with esophageal cancer. Our aim was to evaluate whether a novel prognostic indicator-the log odds of positive lymph nodes (LODDS)-predicts survival in esophageal cancer. METHODS: Patients who underwent esophagectomy for esophageal cancer between 1988 and 2007 were identified from the Surveillance, Epidemiology, and End Results (SEER) database of 18 registries, and a Chinese patient cohort was subjected to validation. The prognostic efficacy of LNM, LNR, and LODDS was compared. Prognostic performance was measured using Harrell's C-index statistic, Schemper's proportion of explained variation, and the Akaike information criterion (AIC). RESULTS: A total of 4,123 patients in the SEER database and 134 patients in the Chinese cohort met our criteria in this study. LODDS gave a better prognostic performance than either LNM or LNR in both the SEER database and the Chinese cohort. Multivariate analyses showed significant values for LNM, LNR, and LODDS as prognostic factors (p < 0.001). However, only LODDS was a significant prognostic factor regardless of the number of lymph nodes retrieved (p = 0.677). Furthermore, after stratification of patients with no nodes involved or all nodes involved, the values of LODDS still distinguished the heterogeneity efficiently. CONCLUSIONS: LODDS predicts survival more accurately than either LNM or LNR in patients undergoing resection for esophageal cancer, especially for patients with an insufficient number of lymph nodes retrieved.

Clinical Characteristics and Prognostic Significance of TERT Promoter Mutations in Cancer: A Cohort Study and a Meta-Analysis.

BACKGROUND: The prevalence of telomerase reverse transcriptase (TERT) promoter mutations (pTERTm) in non-small-cell lung cancer (NSCLC) have been investigated, but the results were inconsistent. In addition, several studies have analysed the role of pTERTm in the etiology of various types of cancers, however, the results also remain inconsistent. METHODS: The genomic DNA sequence of 103 NSCLC samples were analysed to investigate the frequency of pTERTm in these patients and to establish whether these mutations are associated with their clinical data. Furthermore, a meta-analysis based on previously published articles and our cohort study was performed to investigate the association of pTERTm with patient gender, age at diagnosis, metastasis status, tumour stage and cancer prognosis (5-year overall survival rate). RESULTS: In the cohort study, 4 patients had C228T and 2 had C250T, with a total mutation frequency up to 5.8%. Significant difference of clinical data between pTERTm carriers and noncarriers was only found in age at diagnosis. In the meta-analysis, We found that pTERTm carriers in cancer patients are older than noncarriers (Mean difference (MD) = 5.24; 95% confidence interval [CI], 2.00 to 8.48), male patients were more likely to harbour pTERTm (odds Ratios (OR) = 1.38; 95% CI, 1.22 to 1.58), and that pTERTm had a significant association with distant metastasis (OR = 3.78; 95% CI, 2.45 to 5.82), a higher tumour grade in patients with glioma (WHO grade III, IV vs. I, II: OR, 2.41; 95% CI, 1.88 to 3.08) and a higher tumour stage in other types of cancer (III, IV vs. I, II: OR, 2.48; 95% CI, 1.48 to 4.15). pTERTm was also significantly associated with a greater risk of death (hazard ratio = 1.71; 95% CI, 1.41 to 2.08). CONCLUSIONS: pTERTm are a moderately prevalent genetic event in NSCLC. The current meta-analysis indicates that pTERTm is associated with patient age, gender and distant metastasis. It may serves as an adverse prognostic factor in individuals with cancers.

Telomerase Cajal body protein 1 depletion inhibits telomerase trafficking to telomeres and induces G1 cell cycle arrest in A549 cells.

Telomerase Cajal body protein 1 (TCAB1) is a telomerase holoenzyme, which is markedly enriched in Cajal bodies (CBs) and facilitates the recruitment of telomerase to CBs in the S phase of the cell cycle. This recruitment is dependent on TCAB1 binding to a telomerase RNA component. The majority of cancer cells are able to grow indefinitely due to telomerase and its mechanism of trafficking to telomeres. In the present study, a certain level of TCAB1 expression in A549 human lung cells was identified and TCAB1 knockdown exhibited a potent antiproliferative effect on these cells, which was coupled with a decrease in the cell density and activity of the cellular enzymes. In addition, TCAB1-depletion was demonstrated to inhibit telomerase trafficking to telomeres in the A549 cells, leading to subsequent G1 cell cycle arrest without inducing apoptotic cell death. Overall, these observations indicated that TCAB1 may be essential for A549 cell proliferation and cell cycle regulation, and may be a potential candidate for the development of a therapeutic target for lung adenocarcinomas.

Predictive risk factors for lymph node metastasis in patients with small size non-small cell lung cancer.

BACKGROUND: Accurate clinical staging of non-small cell lung cancer (NSCLC) is essential for developing an optimal treatment strategy. This study aimed to determine the predictive risk factors for lymph node metastasis, including both N1 and N2 metastases, in clinical T1aN0 NSCLC patients. METHODS: We retrospectively evaluated clinical T1aN0M0 NSCLC patients who showed no radiologic evidence of lymph node metastasis, and who had undergone surgical pulmonary resection with systematic mediastinal node dissection or sampling at the First Affiliated Hospital of Zhejiang University between January 2011 and June 2013. Univariate and multivariate logistic regression analyses were performed to identify predictive factors for node metastasis. RESULTS: Pathologically positive lymph nodes were found in 16.2% (51/315) of the patients. Positive N1 nodes were found in 12.4% (39/315) of the patients, and positive N2 nodes were identified in 13.0% (41/315) of the patients. Some 9.2% (29/315) of the patients had both positive N1 and N2 nodes, and 3.8% (12/315) of the patients had nodal skip metastasis. Variables of preoperative radiographic tumor size, non-upper lobe located tumors, high carcinoembryonic antigen (CEA) levels and micropapillary predominant adenocarcinoma (AC) were identified as predictors for positive N1 or N2 node multivariate analysis. CONCLUSIONS: Pathologically positive lymph nodes were common in small size NSCLC patients with clinical negative lymph nodes. Therefore, preoperative staging should be performed more thoroughly to increase accuracy, especially for patients who have the larger size, non-upper lobe located, high CEA level or micropapillary predominant ACs.