Advancing NSCLC pathological subtype prediction with interpretable machine learning: a comprehensive radiomics-based approach.

Objective: This research aims to develop and assess the performance of interpretable machine learning models for diagnosing three histological subtypes of non-small cell lung cancer (NSCLC) utilizing CT imaging data. Methods: A retrospective cohort of 317 patients diagnosed with NSCLC was included in the study. These individuals were randomly segregated into two groups: a training set comprising 222 patients and a validation set with 95 patients, adhering to a 7:3 ratio. A comprehensive extraction yielded 1,834 radiomic features. For feature selection, statistical methodologies such as the Mann-Whitney U test, Spearman's rank correlation, and one-way logistic regression were employed. To address data imbalance, the Synthetic Minority Over-sampling Technique (SMOTE) was utilized. The study designed three distinct models to predict adenocarcinoma (ADC), squamous cell carcinoma (SCC), and large cell carcinoma (LCC). Six different classifiers, namely Logistic Regression, Support Vector Machine, Decision Tree, Random Forest, eXtreme Gradient Boosting (XGB), and LightGBM, were deployed for model training. Model performance was gauged through accuracy metrics and the area under the receiver operating characteristic (ROC) curves (AUC). To interpret the diagnostic process, the Shapley Additive Explanations (SHAP) approach was applied. Results: For the ADC, SCC, and LCC groups, 9, 12, and 8 key radiomic features were selected, respectively. In terms of model performance, the XGB model demonstrated superior performance in predicting SCC and LCC, with AUC values of 0.789 and 0.848, respectively. For ADC prediction, the Random Forest model excelled, showcasing an AUC of 0.748. Conclusion: The constructed machine learning models, leveraging CT imaging, exhibited robust predictive capabilities for SCC, LCC, and ADC subtypes of NSCLC. These interpretable models serve as substantial support for clinical decision-making processes.

Different treatment modalities on the prognosis of patients with stage I-IIIa small cell lung cancer: a population based study.

Background: Several studies have shown that surgery may improve prognosis in patients with limited-stage small cell lung cancer (LS-SCLC). This study aimed to compare the effects of different treatment modalities on lung cancer specific survival (LCSS) and overall survival (OS) in LS-SCLC patients. Methods: The Surveillance, Epidemiology and End Results (SEER) database was used to identify patients diagnosed with LS-SCLC. Kaplan-Meier analysis was used to determine the effect of each factor on LCSS and OS. Multivariate analysis was used to analyze the relationship between patient characteristics and survival of different treatment modalities. Results: After a series of screening steps, this study ultimately analyzed the prognosis of patients with stage I-IIIa SCLC under different treatment modalities. The results showed that lobectomy plus postoperative chemoradiotherapy was significantly better than chemoradiotherapy or lobectomy in treatment (all P<0.05). For stage II and IIIA patients, lobectomy plus postoperative chemotherapy ± radiotherapy had similar efficacy to chemoradiotherapy in improving patients' LCSS and OS (all P>0.05), and lobectomy plus postoperative chemotherapy ± radiotherapy did not significantly improve LCSS or OS compared with lobectomy (all P>0.05). Conclusions: For stage II-IIIa SCLC patients, lobectomy might have similar efficacy to chemoradiotherapy in improving LCSS and OS, and there is no need for adjuvant chemotherapy ± radiotherapy after surgery. For stage I SCLC patients, lobectomy plus postoperative chemoradiotherapy might be superior to chemoradiotherapy or lobectomy in improving LCSS and OS; however, the conclusion might be biased. These results suggest that the effect of surgery on SCLC patients may be worthy of further study.

Exploring the link between walking and lung cancer risk: a two-stage Mendelian randomization analysis.

BACKGROUND: Previous observational research showed a potential link between physical activities such as walking and the risk of lung cancer. However, Mendelian randomization (MR) studies suggested there was no association between moderate to vigorous physical activity and lung cancer risk. We speculated that specific physical activities may be associated with lung cancer risk. Consequently, we conducted an MR study to examine the potential relationship between walking and the risk of lung cancer. METHODS: We collected genetic summary data from UK Biobank. After excluding SNPs with F values less than 10 and those associated with confounding factors, we conducted a MR analysis to assess the causal effects between different types of walk and lung cancer. We also performed sensitivity analysis to validate the robustness of our findings. Finally, we analyzed the possible mediators. RESULTS: MR analysis showed number of days/week walked for 10 + minutes was associated with a reduced risk of lung cancer risk (OR = 0.993, 95% CI = 0.987-0.998, P = 0.009). Additionally, usual walking pace was identified as a potentially significant factor in lowering the risk (OR = 0.989, 95% CI = 0.980-0.998, P = 0.015). However, duration of walks alone did not show a significant association with lung cancer risk (OR = 0.991, 95%CI = 0.977-1.005, P = 0.216). The sensitivity analysis confirmed the robustness of these findings. And number of days/week walked for 10 + minutes could affect fed-up feelings and then lung cancer risk. There was a bidirectional relationship between usual walking pace and sedentary behaviors (time spent watching TV). CONCLUSION: The study unveiled a genetically predicted causal relationship between number of days/week walked for 10 + minutes, usual walking pace, and the risk of lung cancer. The exploration of potential mediators of walking phenotypes and their impact on lung cancer risk suggests that specific physical activities may reduce the risk of lung cancer.

A small-sized tube versus traditional closed thoracic drainage in uniportal thoracoscopic surgery.

Introduction: To assess the feasibility and safety of placing a small-sized tube as drainage in patients after uniportal thoracoscopic lung resection. Patients and Methods: Patients who received uniportal video-assisted thoracoscopic surgery (U-VATS) lung resection were identified in our database. Patients placed small-sized tube drainage were compared with those placed conventional chest tube in terms of characteristics, operation modality, post-operative pulmonary complications, post-operative pain, chest tube duration and post-operative hospital stay. Propensity score matching was performed. Results: Of the 217 enrolled patients, 173 were assigned to the conventional tube group and 44 were assigned to the small-sized tube group. Rates of post-operative pulmonary complications were relatively low and similar between the two groups. After propensity score matching, operation duration was shorter (1 h vs. 1.21 h, P = 0.01) was shorter, and the maximum value of the Visual Analogue Scale (VAS) score after operation (1 vs. 1.5, P = 0.02) and the overall average value of VAS score after operation (0.33 vs. 0.88, P = 0.006) was lower in small-sized tube group. No significant difference was observed in chest tube duration (2 vs. 2, P = 0.34) and post-operative hospital stay (3 vs. 3, P = 0.34). Conclusions: Compared to conventional chest tubes, small-sized tubes for post-operative drainage after U-VATS lung resection may be a safe and promising approach for reducing post-operative pain.

The value of folate receptor-positive circulating tumour cells as a diagnostic biomarker for lung cancer: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis evaluating the diagnostic value of folate receptor-positive (FR+) circulating tumour cells (CTCs) as a potential tumour marker for lung cancer diagnosis. METHODS: The PubMed, Embase, and Web of Science databases were searched for relevant articles published between database inception and November 2022. Eligible studies were selected based on inclusion and exclusion criteria. Sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and area under the curve (AUC) were pooled with 95% confidence intervals (CI), using RevMan 5.4 and STATA 17.0 software to assess the diagnostic value of FR+CTC for lung cancer. RESULTS: After screening, 11 studies involving 3469 subjects were eligible for inclusion. The pooled sensitivity and specificity were 0.79 (95% CI 0.76, 0.82) and 0.84 (95% CI 0.81, 0.96), respectively, and the pooled positive and negative likelihood ratios were 4.90 (95% CI 4.25, 5.65) and 0.25 (95% CI 0.22, 0.29), respectively. The pooled diagnostic odds ratio was 19.70 (95% CI 16.06, 24.16). The AUC of the pooled summary receiver operating characteristic curve was 0.89 (95% CI 0.85, 0.91). Sensitivity analysis showed that this result was stable after one-by-one study elimination. CONCLUSION: Folate receptor-positive CTCs may have good diagnostic value in lung cancer.

Assessment of preoperative anxiety and depression in patients with pulmonary ground-glass opacities: Risk factors and postoperative outcomes.

Objective: A large number of patients with pulmonary ground-glass opacities (GGOs) have anxiety and depression. However, the contributing factors and effects of anxiety and depression on postoperative outcomes are still unclear. Methods: Clinical data for patients undergoing surgical resection for pulmonary GGOs were collected. We prospectively evaluated levels and risk factors for anxiety and depression in patients with GGOs before surgery. The relationship between psychological disorders and postoperative morbidity was evaluated. Quality of life (QoL) was also assessed. Results: A total of 133 patients were enrolled. Prevalence rates of preoperative anxiety and depression were 26.3% (n = 35) and 18% (n = 24), respectively. Multivariate analysis revealed depression [odds ratio(OR) = 16.27, p < 0.001] and multiple GGOs (OR = 3.146, p = 0.033) to be risk factors for preoperative anxiety. Anxiety (OR = 52.166, p < 0.001), age > 60 (OR = 3.601, p = 0.036), and unemployment (OR = 8.248, p = 0.006) were identified as risk factors for preoperative depression. Preoperative anxiety and depression were associated with lower QoL and higher postoperative pain scores. Our results also revealed that the incidence of postoperative atrial fibrillation was higher in patients with than in those without anxiety. Conclusions: In patients with pulmonary GGOs, comprehensive psychological assessment and appropriate management are required before surgery to improve QoL and reduce postoperative morbidity.

E2F1-activated LINC01224 drives esophageal squamous cell carcinoma cell malignant behaviors via targeting miR-6884-5p/DVL3 axis and activating Wnt/ß-catenin signaling pathway.

Current evidence has unveiled that long non-coding RNAs (lncRNAs) are pivotal regulators in the development of cancers. This study aimed to investigate the potential mechanisms of LINC01224 in esophageal squamous cell carcinoma (ESCC) cells. RT-qPCR analysis was done to test LINC01224 expression in ESCC cells. Functional assays were conducted to assess the influences of LINC01224 on ESCC cell functions. Mechanism assays were carried out to detect the regulatory mechanisms of LINC01224 at post-transcriptional and transcriptional levels. Briefly, LINC01224 expression was remarkably high in ESCC cells. LINC01224 silence restricted the proliferative, migratory, and invasive capabilities of ESCC cells. Moreover, LINC01224 could combine with miR-6884-5p by acting as a ceRNA. Further, DVL3 was proved to be targeted by miR-6884-5p. Importantly, LINC01224 could switch on Wnt/ß-catenin signaling pathway by via enhancing DVL3 expression. Additionally, E2F1 could serve as a transcription factor to stimulate LINC01224 transcription. In summary, our study elucidated that E2F1-activated LINC01224 regulated miR-6884-5p/DVL3 to actuate the Wnt/ß-catenin signaling pathway, which facilitates multiple phenotype of ESCC cells, including proliferation, migration, and invasion. Our findings might offer potential therapeutic targets for ESCC treatment.

The Functionalities and Clinical Significance of Tumor-Infiltrating Immune Cells in Esophageal Squamous Cell Carcinoma.

Tumor-infiltrating immune cells have been implicated in the tumorigenesis and progression of esophageal squamous cell carcinoma (ESCC). However, the functionalities and clinical significance of immune cells remain largely unveiled. In this study, the gene expression data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were extracted. The relative infiltrating levels were estimated by single-sample gene set enrichment analysis. Some cytotoxic immune cells were attenuated, and resting cytotoxic immune cells were accumulated in ESCC. Remarkably, we also observed that infiltrating levels of macrophage M2 and resting natural killer (NK) cells were increased in nonresponders of CRT, and T cells that had anticancer activities such as activated memory CD4 and T helper 2 (Th2) cells were significantly reduced in ESCC tissues of the nonresponders. Moreover, the high infiltrations of the resting natural killer (NK) and dendritic cell (DC) were observed to result in a shorter overall survival in ESCC. Consistently, high expression of immune checkpoint genes, CTLA4 and HAVCR2, was associated with poor prognosis. Furthermore, STAT5B, a key transcription factor, as well as its target genes, involved in the regulation of T cells, was significantly downregulated in ESCC, especially subgroup I, indicating that downregulation of STAT5B might be associated with reduced T cell-mediated anticancer activity. In conclusion, the present study significantly improved our understanding of the regulatory roles of immune cells in ESCC.

Novel lncRNA Panel as for Prognosis in Esophageal Squamous Cell Carcinoma Based on ceRNA Network Mechanism.

BACKGROUND: The competitive endogenous RNA (ceRNA) mechanism has been discovered recently and regulating cancer-related gene expressions. The ceRNA network participates in multiple processes, such as cell proliferation and metastasis, and potentially drives the progression of cancer. In this study, we focus on the ceRNA networks of esophageal squamous cell carcinoma and discovered a novel biomarker panel for cancer prognosis. METHODS: RNA expression data of esophageal carcinoma from the TCGA database were achieved and constructed ceRNA network in esophageal carcinoma using R packages. RESULTS: Four miRNAs were discovered as the core of the ceRNA model, including miR-93, miR-191, miR-99b, and miR-3615. Moreover, we constructed a ceRNA network in esophageal carcinoma, which included 4 miRNAs and 6 lncRNAs. After ceRNA network modeling, we investigated six lncRNAs which could be taken together as a panel for prognosis prediction of esophageal cancer, including LINC02575, LINC01087, LINC01816, AL136162.1, AC012073.1, and AC117402.1. Finally, we tested the predictive power of the panel in all TCGA samples. CONCLUSIONS: Our study discovered a new biomarker panel which may have potential values in the prediction of prognosis of esophageal carcinoma.

ACOT11 promotes cell proliferation, migration and invasion in lung adenocarcinoma.

BACKGROUND: Lung cancer is one of the most common cancers in the word. However, the underlying mechanism remains largely unknown. ACOT11 encodes enzymes hydrolyzing the fatty acyl-CoA esters into free fatty acids and CoA. Besides from its role in fatty acid metabolism, the other aspects regarding its function in the progression of lung cancer have not been revealed. METHODS: We first explored the clinical profile of ACOT11 in tumor samples. Next, we combined gene knockdown in vitro and in vivo and microarray gene profiling analysis to decipher the unknown regulatory role of ACOT11 in lung cancer carcinoma. Furthermore, we explored the potential molecular mechanisms of ACOT11 with immunoprecipitation. RESULTS: We found high expression of ACOT11 in tumor samples. High expression of ACOT11 showed significantly poor prognosis in lung squamous carcinoma (LUSC) patients. Knocking down of ACOT11 inhibited the cell proliferation, migration as well as invasion in vitro and in vivo. It also promoted the cell apoptosis and cell cycle arrest via multiple signaling pathways. Additionally, ACOT11 could bind with CSE1L, which was proved to be an oncogene in lung cancer and speculated to be a potential target of ACOT11. CONCLUSIONS: The results revealed that ACOT11 regulates proliferation, migration and invasion of lung cancer carcinoma via multiple signaling pathways, indicating its potential value in molecular therapy.

Morphogenesis and cytopathic effect of SARS-CoV-2 infection in human airway epithelial cells.

SARS-CoV-2, a ß-coronavirus, has rapidly spread across the world, highlighting its high transmissibility, but the underlying morphogenesis and pathogenesis remain poorly understood. Here, we characterize the replication dynamics, cell tropism and morphogenesis of SARS-CoV-2 in organotypic human airway epithelial (HAE) cultures. SARS-CoV-2 replicates efficiently and infects both ciliated and secretory cells in HAE cultures. In comparison, HCoV-NL63 replicates to lower titers and is only detected in ciliated cells. SARS-CoV-2 shows a similar morphogenetic process as other coronaviruses but causes plaque-like cytopathic effects in HAE cultures. Cell fusion, apoptosis, destruction of epithelium integrity, cilium shrinking and beaded changes are observed in the plaque regions. Taken together, our results provide important insights into SARS-CoV-2 cell tropism, replication and morphogenesis.

Prognostic value of neuron-specific enolase for small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Neuron-specific enolase (NSE) has become a widely used and easily attainable laboratory assay of small cell lung cancer (SCLC). However, the prognostic value of NSE for SCLC patients remains controversial. The aim of the study was to evaluate the correlation between elevated serum NSE before therapy and survival of SCLC patients. METHODS: We performed a systematic review and meta-analysis. A systematic literature search was conducted in PubMed, Embase, and the Cochrane Central Register from the inception dates to December 2019. Eligible articles were included according to inclusion and exclusion criteria; then, data extraction and quality assessment were performed. The primary outcome was overall survival (OS), and the secondary endpoint was progression-free survival (PFS). RESULTS: We identified 18 studies comprising 2981 patients. Pooled results revealed that elevated NSE was associated with worse OS (HR = 1.78, 95% CI 1.55-2.06, p < 0.001) and PFS (HR = 1.50, 95% CI 1.16-1.93, p = 0.002). In subgroup analysis, elevated NSE did not predict worse OS in patients who received only chemotherapy (HR 1.22, 95% CI 0.96-1.55, p = 0.10) or part of whom received surgical resection before chemotherapy and radiotherapy (HR = 2.16, 95% CI 0.82-5.69, p = 0.12). CONCLUSION: Elevated serum NSE before any therapy of SCLC patients may be a negative prognostic factor for OS and PFS. The prognostic value of NSE for OS was particularly observed in patients treated by standard management.

Knockdown of actin-like 8 inhibits cell proliferation by regulating FOXM1, STMN1, PLK1, and BIRC5 in lung adenocarcinoma A549 cells.

BACKGROUND: Actin-like protein 8 (ACTL8) is a member of the CTA family, and it is expressed in various types of cancer, including glioblastoma and breast cancer. However, whether ACTL8 is involved in the development of lung adenocarcinoma (LUAD) remains unknown. Here, we try to demonstrate the role of ACTL8 in human LUAD A549 cells. METHODS: First, the high expression of ACTL8 was observed in patients with LUAD via immunohistochemistry (IHC) staining. Second, cell proliferation was significantly inhibited in ACTL8 knockdown A549 cells. Third, a global gene expression analysis was performed to discover the potential genes and signal pathways modulated by ACTL8 in A549 cells. RESULTS: A total of 504 differentially expressed genes (DEGs) (146 up-regulated, and 358 down-regulated) were found in the ACTL8 knockdown A549 cells compared with the mock-transfected cells. Ingenuity pathway analysis (IPA) revealed that canonical pathways such as cyclins and cell cycle regulation and estrogen-mediated S-phase entry were significantly inhibited, while pathways such as cell cycle: G2/M DNA damage checkpoint regulation and HMGB1 signaling were significantly activated by ACTL8 knockdown. Disease and functions enrichment analysis revealed that processes associated with "cell death" and "apoptosis" were significantly activated. Upstream regulator analysis showed that NUPR1 was the most activated, while CSF2 was the most inhibited. Lastly, a qRT-PCR and Western blot analysis further confirmed that the expression levels of FOXM1, STMN1, PLK1, and BIRC5 were markedly reduced in ACTL8 knockdown of A549 cells. CONCLUSIONS: In summary, these results suggest that a knockdown of ACTL8 inhibits cell proliferation in human LUAD A549 cells by regulating FOXM1, STMN1, PLK1, and BIRC5.

High CCR4 expression in the tumor microenvironment is a poor prognostic indicator in lung adenocarcinoma.

BACKGROUND: Clinical trials of anti-CCR4 antibody for solid cancers with or without other immune-modulating agents including immune checkpoint blockade therapy are currently underway. However, little is known about the roles of CCR4+ lymphocytes and their prognostic impact in lung cancer. We hypothesized that high CCR4 expression in the tumor microenvironment would be associated with a poor prognosis and would act as a biomarker in lung adenocarcinoma. METHODS: First, the prognostic impact of CCR4 gene expression was explored using pooled data from public transcriptomic databases with online survival analysis software. Second, tissue microarrays (TMAs) were constructed from resected lung adenocarcinoma specimens from tumors up to 3 cm in size. The density of CCR4+ lymphocytes infiltrating the tumor was then assessed by immunohistochemistry and related to survival. Confounding factors were controlled for by multivariate analysis using the Cox proportional hazards model. RESULTS: Higher than median expression of the CCR4 gene was identified as an independent poor prognostic factor for overall survival (OS) by multivariate analysis of 720 lung adenocarcinoma patients in the public databases [HR =1.55 (95% CI: 1.03-2.35), P=0.037]. Consistent with this, high CCR4+ tumor-infiltrating lymphocyte (TIL) density was found to be an independent poor prognostic factor for both OS [HR =2.24 (1.01-5.34), P=0.049] and recurrence-free survival (RFS) [HR =2.20 (1.16-4.39), P=0.017] in the patients from whom TMA were obtained (n=180). Age, male gender, predominantly non-lepidic histological subtype, nodal involvement, and low CD8+ TIL density were also independent poor prognostic factors. However, FOXP3 gene expression and Foxp3+ lymphocyte infiltration did not possess any prognostic value in either study. CONCLUSIONS: High CCR4 expression in the tumor microenvironment may be a poor prognostic factor in lung adenocarcinoma. Patients with high CCR4+ lymphocyte infiltration may have a poor prognosis and thus be suitable candidates for clinical trials of anti-CCR4 antibody treatment.

[Impact of Chronic Obstructive Pulmonary Disease on Risk of Recurrence in Patients with Resected Non-small Cell Lung Cancer].

BACKGROUND: Lung cancer and chronic obstructive pulmonary disease (COPD) are both common diseases in respiratory system and the leading causes of deaths worldwide. The purpose of this study was to determine whether the severity of COPD affects long-term survival in non-small cell lung cancer (NSCLC) patients after surgical resection. METHODS: A retrospective research was performed on 421 consecutive patients who had undergone lobectomy for NSCLC. Classification of COPD severity was based on guidelines of the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Characteristics among the three subgroups were compared and recurrence-free survivals were analyzed. RESULTS: A total of 172 patients were diagnosed with COPD, 124 as mild (GOLD-1), 46 as moderate(GOLD-2), and 2 as severe (GOLD-3). The frequencies of recurrence were significantly higher in higher COPD grades group (P<0.001). Recurrence-free survival at five years were 78.1%, 70.4%, and 46.4% in Non-COPD, GOLD-1 COPD, and GOLD-2/3 COPD groups, respectively (P<0.001). In univariate analysis, age, gender, smoking history, COPD severity, tumor size, histology and pathological stage were associated with recurrence-free survival. Multivariate analyses showed that older age, male, GOLD-2/3 COPD, and advanced stage were independent risk factors associated with recurrence-free survival. CONCLUSIONS: NSCLC patients with COPD are at higher risk for postoperative recurrence, and moderate/severe COPD is an independent unfavorable prognostic factor. The severity of COPD based on pulmonary function test can be a useful indicator to identify patients at high risk for recurrence. Therefore, it can contribute to adequate selection of the appropriate individualized treatment.

Proteasome Inhibitor YSY01A Enhances Cisplatin Cytotoxicity in Cisplatin-Resistant Human Ovarian Cancer Cells.

Cisplatin is one of the most common drugs used for treatment of solid tumors such as ovarian cancer. Unfortunately, the development of resistance against this cytotoxic agent limits its clinical use. Here we report that YSY01A, a novel proteasome inhibitor, is capable of suppressing survival of cisplatin-resistant ovarian cancer cells by inducing apoptosis. And YSY01A treatment enhances the cytotoxicity of cisplatin in drug-resistant ovarian cancer cells. Specifically, YSY01A abrogates regulatory proteins important for cell proliferation and anti-apoptosis including NF-κB p65 and STAT3, resulting in down-regulation of Bcl-2. A dramatic increase in cisplatin uptake was also observed by inductively coupled plasma-mass spectrometry following exposure to YSY01A. Taken together, YSY01A serves as a potential candidate for further development as anticancer therapeutics targeting the proteasome.

Association between histopathological subtype, 18F-fluorodeoxyglucose uptake and epidermal growth factor receptor mutations in lung adenocarcinoma.

The aim of the present study was to investigate the association between histopathological subtypes, epidermal growth factor receptor (EGFR) mutations and 18F-fluorodeoxyglucose (FDG) uptake in patients with lung adenocarcinoma (ADC). The cases of 97 patients with lung ADC who underwent 18F-FDG positron emission tomography-computed tomography prior to surgical resection were retrospectively reviewed. The patients were stratified according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification, and graded using a histopathological scoring system. EGFR mutations were identified. Clinicopathological characteristics associated with EGFR mutation status were evaluated using univariate and multivariate analyses. EGFR mutation was identified in 45.4% of the patients and was associated with gender, smoking history, maximum standardized uptake value (SUVmax) and histopathological score. ADC patients with a low SUVmax were more likely to exhibit EGFR mutations compared with patients with a high SUVmax (P=0.018). Patients with a lower histopathological score possessed a significantly lower SUVmax compared with patients with a higher score (P<0.001). Furthermore, the histopathological score and smoking history of the patients were identified to be independent predictors for EGFR mutations, according to multivariate logistic regression analysis. In conclusion, SUVmax and EGFR mutations were associated with lung ADC patients stratified according to the IASLC/ATS/ERS classification. Overall, SUVmax has the potential to be a useful marker in stratifying pre-operative patients with lung ADC and identifying EGFR mutations.

Prognostic significance of platelet-to-lymphocyte ratio in non-small-cell lung cancer: a meta-analysis.

BACKGROUND: The platelet-to-lymphocyte ratio (PLR) is a useful predictive factor in several cancers. However, the prognostic value of PLR in patients with non-small-cell lung cancer (NSCLC) is still indistinct. Therefore, it was necessary for us to perform a meta-analysis to assess the prognostic value of PLR in patients with NSCLC. METHODS: A systematic literature search was performed by using PubMed, EMBASE, and Web of Science databases for relevant studies until May 2015. Published studies investigating the association between PLR and overall survival (OS) and disease-free survival (DFS) were selected. Data from each eligible study were extracted. A meta-analysis was performed to analyze the prognostic value of PLR by using the hazard ratio (HR) and 95% confidence intervals (95% CI). RESULTS: A total of seven studies involving 1,554 patients were included in our meta-analysis. Our pooled results demonstrated that high PLR was associated with poor OS (HR: 1.60, 95% CI: 1.34-1.90, I (2)=22.3%, P heterogeneity = 0.259) and DFS (HR: 1.38, 95% CI: 1.11-1.73, I 2=0%, P heterogeneity = 0.482). Subgroup analysis between PLR and OS was performed in a further investigation. When the patients were segregated according to ethnicity, sample size, cutoff value, stage, and treatment modality, high PLR was also significantly correlated with OS. There was no significant heterogeneity among included studies. CONCLUSION: High PLR is associated with poor prognosis in patients with NSCLC. PLR may be a significant predictive biomarker in patients with NSCLC.

Impact of chronic obstructive pulmonary disease on postoperative recurrence in patients with resected non-small-cell lung cancer.

PURPOSE: This study aimed to determine whether the severity of chronic obstructive pulmonary disease (COPD) affects recurrence-free survival in non-small-cell lung cancer (NSCLC) patients after surgical resection. PATIENTS AND METHODS: A retrospective study was performed on 421 consecutive patients who had undergone lobectomy for NSCLC from January 2008 to June 2011. Classification of COPD severity was based on guidelines of the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Characteristics among the three subgroups were compared and recurrence-free survivals were analyzed. RESULTS: A total of 172 patients were diagnosed with COPD (124 as GOLD-1, 46 as GOLD-2, and two as GOLD-3). The frequencies of recurrence were significantly higher in patients with higher COPD grades (P<0.001). Recurrence-free survival at 5 years was 78.1%, 70.4%, and 46.4% in non-COPD, mild COPD, and moderate/severe COPD groups, respectively (P<0.001). By univariate analysis, the age, sex, smoking history, COPD severity, tumor size, histology, and pathological stage were associated with recurrence-free survival. Multivariate analysis showed that older age, male, moderate/severe COPD, and advanced stage were independent risk factors associated with recurrence-free survival. CONCLUSION: NSCLC patients with COPD are at high risk for postoperative recurrence, and moderate/severe COPD is an independent unfavorable prognostic factor.

[The prognostic impact of preoperative PET-CT on postoperative recurrence for completely resected stage I non-small cell lung cancer].

OBJECTIVE: To analyze the prognostic impact of preoperative (18)F-fluorodeoxyglucose (FDG) PET-CT on postoperative recurrence in patients with completely resected stage I non-small cell lung cancer (NSCLC). METHODS: The clinic data of 182 patients with stage I NSCLC who underwent (18)F-FDG PET-CT scan before surgical resection between June 2005 and June 2012 were reviewed retrospectively. There were 121 male and 61 female patients, with an average age of 68 years (range from 34 to 85 years). The pathological stage was I A in 98 patients, I B in 84 patients; the histology were adenocarcinoma in 137 patients, squamous cell carcinoma in 35 patients, and others in 10 patients. Clinicopathological factors including gender, age, smoking history, SUV(max), surgical procedure, pathological features and adjuvant chemotherapy were evaluated to identify the independent factors predicting postoperative recurrences by univariate and multivariate analysis. The survivals were calculated by the Kaplan-Meier method and differences in variables were analyzed by the Log-rank test. RESULTS: The postoperative recurrence rate was 15.9%. The univariate analysis identified that the SUV(max) (t=3.278, P<0.001), p-stage (χ² =5.204, P=0.026), blood vessel invasion (χ² =5.333, P=0.027) and visceral pleural invasion (χ² =7.697, P=0.009) are factors for predicting postoperative recurrence. Only SUV(max) was found to be a significant independent factor according to multivariate analysis (HR=1.068, 95%CI: 1.015 to 1.123, P=0.001). The study population was stratified into three groups by SUV(max), patients with SUV(max) > 5.0 had significantly higher risk of recurrence (23.9%) than those with 2.5 < SUV(max) ≤ 5.0 (15.0%) and SUV(max) ≤ 2.5 (7.3%) (P=0.043); patients with SUV(max) ≤ 2.5 had significantly better 5-year recurrence-free survival rate (90.9%) than those with 2.5 < SUV(max) ≤ 5.0 (82.7%) and SUV(max) ≤ 2.5 (71.0%) (P=0.030). There was a trend toward higher probability of blood vessel invasion (χ² =20.267, P < 0.001), visceral pleural invasion (χ² =6.185, P=0.045) and pathological stage I B (χ² =13.589, P=0.001) with increased SUV(max). CONCLUSIONS: Preoperative SUV(max) of primary tumor is a predictor of postoperative relapse for stage I NSCLC after surgical resection. Therefore, it can contribute to the risk stratification for patients with the same pathological stage and selecting the optimal postoperative follow-up and therapeutic strategy.