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Abstract Background Pneumonia and lung cancer are both major respiratory diseases, and observational studies have explored the association between their susceptibility. However, due to the presence of potential confounders and reverse causality, the comprehensive causal relationships between pneumonia and lung cancer require further exploration. Methods Genome-wide association study (GWAS) summary-level data were obtained from the hitherto latest FinnGen database, COVID-19 Host Genetics Initiative resource, and International Lung Cancer Consortium. We implemented a bidirectional Mendelian randomization (MR) framework to evaluate the causal relationships between several specific types of pneumonia and lung cancer. The causal estimates were mainly calculated by inverse-variance weighted (IVW) approach. Additionally, sensitivity analyses were also conducted to validate the robustness of the causalty. Results In the MR analyses, overall pneumonia demonstrated a suggestive but modest association with overall lung cancer risk (Odds ratio [OR]: 1.21, 95% confidence interval [CI]: 1.01 − 1.44, P = 0.037). The correlations between specific pneumonia types and overall lung cancer were not as significant, including bacterial pneumonia (OR: 1.07, 95% CI: 0.91 − 1.26, P = 0.386), viral pneumonia (OR: 1.00, 95% CI: 0.95 − 1.06, P = 0.891), asthma-related pneumonia (OR: 1.18, 95% CI: 0.92 − 1.52, P = 0.181), and COVID-19 (OR: 1.01, 95% CI: 0.78 − 1.30, P = 0.952). Reversely, with lung cancer as the exposure, we observed that overall lung cancer had statistically crucial associations with bacterial pneumonia (OR: 1.08, 95% CI: 1.03 − 1.13, P = 0.001) and viral pneumonia (OR: 1.09, 95% CI: 1.01 − 1.19, P = 0.037). Sensitivity analysis also confirmed the robustness of these findings. Conclusion This study has presented a systematic investigation into the causal relationships between pneumonia and lung cancer subtypes. Further prospective study is warranted to verify these findings.

Abstract Background Immune checkpoint inhibitors (ICI) combined with chemotherapy are efficacious for treating advanced non-small cell lung cancer (NSCLC); however, the effectiveness of this approach in the malignant pleural effusion (MPE) population is unclear. This study evaluated ICI plus chemotherapy in NSCLC patients with MPE. Methods Patients from 3 centers in China with NSCLC and MPE who received ICI plus chemotherapy (ICI Plus Chemo) or chemotherapy alone (Chemo) between December 2014 and June 2023 were enrolled. Clinical outcomes and adverse events (AEs) were compared. Results Of 155 eligible patients, the median age was 61.0 years old. Males and never-smokers accounted for 73.5% and 39.4%, respectively. Fifty-seven and 98 patients received ICI Plus Chemo or Chemo, respectively. With a median study follow-up of 10.8 months, progression-free survival (PFS) was significantly longer with ICI Plus Chemo than with Chemo (median PFS: 7.4 versus 5.7 months; HR = 0.594 [95% CI: 0.403–0.874], P = 0.008). Median overall survival (OS) did not differ between groups (ICI Plus Chemo: 34.2 versus Chemo: 28.3 months; HR = 0.746 [95% CI: 0.420–1.325], P = 0.317). The most common grade 3 or worse AEs included decreased neutrophil count (3 [5.3%] patients in the ICI Plus Chemo group vs. 5 [5.1%] patients in the Chemo group) and decreased hemoglobin (3 [5.3%] versus 10 [10.2%]). Conclusions In patients with untreated NSCLC with MPE, ICI plus chemotherapy resulted in significantly longer PFS than chemotherapy and had a manageable tolerability profile, but the effect on OS may be limited.

Abstract Background Solid pulmonary nodules are different from subsolid nodules and the diagnosis is much more challenging. We intended to evaluate the diagnostic and prognostic value of radiomics and deep learning technologies for solid pulmonary nodules. Methods Retrospectively enroll patients with pathologically-confirmed solid pulmonary nodules and collect clinical data. Obtain pre-treatment high-resolution thoracic CT and manually delineate the nodule in 3D. Then, all patients were randomly divided into training and testing sets at a ratio of 7:3, and convolutional neural networks (CNN) models and random forest (RF) models were established. Survival analyses were performed for patients with solid adenocarcinomas. Results Totally 720 solid pulmonary nodules were enrolled, 348 benign and 372 malignant. The CNN model with clinical features achieved the highest AUC [0.819, 95% confidence interval (CI): 0.760–0.877] with a sensitivity of 0.778, specificity of 0.788 and accuracy of 0.783. No significant differences were observed between the CNN and radiomics models. There were 295 solid adenocarcinomas in survival analysis. Different disease-free survival was observed between the low-risk and high-risk groups divided according to the radiomics Rad-score. However, the groups based on deep learning signatures showed similar survival. Cox regression analysis indicated that the radiomics Rad-score (hazard ratio: 5.08, 95% CI: 2.61–9.90) was an independent predictor of recurrence. Conclusions The radiomics and deep learning models can well predict the malignancy of solid pulmonary nodules. Radiomics signatures also demonstrate prognostic value in solid adenocarcinomas.

Abstract Background Despite much research published on lung cancer screening, China has had no large-scale study on the missed diagnosis of lung cancer in a health examination population. We therefore did a real-world study using the current lung cancer screening guidelines to a health examination population in China to determine the proportion of lung cancer cases that have been missed. Methods A real-world cohort study of screening, with the use of low-dose computed tomography, was conducted among people who took yearly health checkup in health management center of West China Hospital between 2006 and 2017. We respectively used current guidelines including lung cancer screening guidelines of the U.S. Preventive Services Task Force (USPSTF) and expert consensus on low dose spiral CT lung cancer screening in China. Results In a total of 15,996 participants with health examination who completed the baseline screening, 6779 (42.4%) subjects had at least one positive finding, and 142 (2.1%) cases of lung cancer were screened positive. The false positive rate was 97.9%. Of 142 lung cancer cases detected in our study, only 9.2% met the lung cancer screening guidelines proposed by the USPSTF, and 24.4% met that of China. The rates of missed diagnosis were as high as 90.8 and 75.6% respectively. In addition, we did an in-depth analysis by gender. We found that among male patients with lung cancer, the proportion of smokers was 75%, and the proportion of young people under 50 was 23.2%. Among female patients with lung cancer, the proportion of smokers was only 5.8%, and the proportion of young people under 50 was up to 33.3%. Conclusions The rate of missed diagnosis was as high as 90.8% applying the current lung cancer screening guidelines to the health examination population in China. Further study to determine screening guidelines for targeted populations, is warranted.

Abstract Background To investigate clinicopathological variables influencing overall survival, overall recurrence, and post-recurrence survival (PRS) in patients who experienced curative-intent surgical resection of stage I non-small-cell lung cancer (NSCLC). Methods We investigated a series of 1387 patients with stage I NSCLC who underwent surgical resection from 2008 to 2015. The effect clinicopathological factors on death, recurrence, and PRS were evaluated by Kaplan-Meier estimates and cox regression analysis. Results Among the 1387 stage I patients, 301 (21.7%) experienced recurrence. The 5-year cumulative incidence of recurrence (CIR) for all patients was 20.2% and median PRS was 25.5 months. The older age (P = 0.036), p-stage IB (P = 0.001), sublobar resection(P

Abstract Background The liver microenvironment plays a key role in the progression and metastasis of hepatocellular carcinoma (HCC). Gene expression profiling of non-cancerous hepatic tissues obtained from patients with metastatic HCC exhibit a unique immune response signature, including upregulation of CCN3. However, the role of CCN3 secreted from non-cancerous hepatic tissues in the progression of HCC remains unclear. Methods Using tissue microarrays, we examined CCN3 in non-cancerous hepatic tissues of patients with HCC and correlated expression with clinical and pathological features. In addition, CCN3 localization and mechanisms of HCC progression were investigated in tissues and cell lines. Finally, correlations between CCN3 and cirrhosis were explored in patients. Results CCN3 was primarily localized to hepatic cells of non-cancerous hepatic tissues and was associated with vascular invasion and poor prognosis in patients with HCC. CCN3 expression in non-cancerous hepatic tissues also correlated with the degree of liver fibrosis. Compared with conditioned media from wild-type LO2 cells, conditioned media from hepatic cell line LO2 activated by LX2 (aLO2-CM) induced CCN3 expression and HCC cell proliferation and metastasis. Further, aLO2-CM activated MAPK signaling and epithelial-mesenchymal transition in HCC cells. Finally, CCN3 was inversely related to cirrhosis in the prognosis of HCC and negatively regulated hepatic stellate cells (HSCs) in vitro with downregulation of α-SMA, TGF-β, and collagens. Conclusions CCN3 was secreted from hepatic cells activated by HSCs and increased MAPK signaling, EMT, proliferation and metastasis of HCC cells. CCN3 was also inversely related to cirrhosis, regulating HSCs through a negative feedback loop.

Abstract Background Peripheral monocyte count is an assessable parameter. Recently, evidence suggested an elevated preoperative monocyte counts predicting poor prognosis in malignancies. The aim of this study was to determine the prognostic effect of early postoperative blood monocyte count in patients with lung adenocarcinoma or squamous cell carcinoma following lobectomy. Methods We retrospectively reviewed patients with operated lung adenocarcinoma or squamous cell carcinoma from 2006 to 2011 in Western China Lung Cancer database. Univariate analysis on disease-free survival (DFS) and overall survival (OS) was performed using the Kaplan-Meier and log-rank tests, and multivariate analysis was conducted using the Cox proportional hazards regression model. Results There were 433 patients enrolled in our analysis. High postoperative elevated monocyte was associated with male gender (P

Abstract Background The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are easily obtained from routine blood tests. We investigated the associations of the NLR and PLR with the clinical parameters and prognoses of small cell lung cancer (SCLC) patients. Methods Pre-treatment clinical and laboratory data from 139 patients with SCLC were retrospectively studied with univariate analyses. The NLR and PLR values were divided into two separate groups: high NLR (>4.55, n = 32) vs low NLR (≤4.55, n = 107) and high PLR (>148, n = 63) vs low PLR (≤148, n = 76). Kaplan-Meier survival analyses and Cox proportional hazard models were used to examine the effects of NLR and PLR on overall survival. Results Chi-square analyses revealed significant associations of high NLR with tumour stage, hepatic metastasis, radiotherapy and chemotherapy and significant associations of high PLR with tumour stage, bone and hepatic metastases, exposure to cooking oil fumes, and chemotherapy. Mann-Whitney U tests demonstrated an association of high NLR with smoking exposure, and high NLR and high PLR were correlated with several laboratory parameters. Kaplan-Meier analyses revealed that high NLR and high PLR conferred poor prognoses for SCLC patients. Moreover, multivariate analysis demonstrated that NLR, tumour stage, and hepatic metastasis were independent prognostic factors for survival. In this study, we found that NLR and PLR were associated with several factors that reflect the inflammatory (white blood cell count, WBC; lactate dehydrogenase, LDH) and nutritional (albumin, ALB; haemoglobin, HB; and cholesterol) status of SCLC patients at diagnosis. Conclusions NLR is an independent prognostic factor and can be used to predict the mortality risk of SCLC patients.

Background: The roles of carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CYFRA21-1) and neuron-specific enolase (NSE) in metastases occurrence and poor diagnosis in specific histological classifications of lung cancer need further exploring. In this study, we investigated relationship between elevated levels of three biomarkers of CEA, CYFRA21-1 and NSE (individually and in combination) and metastasis, survival status and prognosis in lung cancer patients.Methods: Eight hundred and sixty eight lung cancer patients including adenocarcinoma (ADC, N = 445), squamous cell carcinoma (SCC, N = 215), small cell lung cancer (SCLC, N = 159) and other types (N = 49) were categorized into negative, moderate and high groups according to serum levels of biomarkers, and were then categorized into negative, single, double and triple groups according to any positive combination of three biomarkers. The cutoff values of three biomarkers for groupings were developed on the training group (N = 432) and verified in a validation group (N = 436). Clinical and laboratory characteristics were then assessed for correlation with occurrence of metastasis, survival status and prognosis between the two groups. Further correlation analyses were also conducted by different subtypes (ADC, SCC and SCLC) and tumor stages (I + II, III and IV) of lung cancers.Results: The consistent results between training and validation group confirmed the rationality of grouping methods. CYFRA21-1 levels had stronger association with metastases and survival status than CEA and NSE in all lung cancer patients. When stratified by subtypes, these significances only existed in ADC patients for CYFRA21-1. Cox regression analyses showed that CYFRA21-1 and NSE were independent prognostic factors for lung cancer patients. However, only CYFRA21-1 was an independent prognostic factor in ADC and SCLC patients subtypes. Cox-regression results also indicated that CYFRA21-1 could act as independent prognostic factor in different stages (I + II, III and IV) of lung cancer.Conclusion: CYFRA21-1 was more important in metastasis occurrence and in predicting poor prognosis in lung cancer patients than CEA, NSE and positive numbers of biomarkers. [ABSTRACT FROM AUTHOR]