Multicellular ecotypes shape progression of lung adenocarcinoma from ground-glass opacity toward advanced stages.

Lung adenocarcinoma is a type of cancer that exhibits a wide range of clinical radiological manifestations, from ground-glass opacity (GGO) to pure solid nodules, which vary greatly in terms of their biological characteristics. Our current understanding of this heterogeneity is limited. To address this gap, we analyze 58 lung adenocarcinoma patients via machine learning, single-cell RNA sequencing (scRNA-seq), and whole-exome sequencing, and we identify six lung multicellular ecotypes (LMEs) correlating with distinct radiological patterns and cancer cell states. Notably, GGO-associated neoantigens in early-stage cancers are recognized by CD8+ T cells, indicating an immune-active environment, while solid nodules feature an immune-suppressive LME with exhausted CD8+ T cells, driven by specific stromal cells such as CTHCR1+ fibroblasts. This study also highlights EGFR(L858R) neoantigens in GGO samples, suggesting potential CD8+ T cell activation. Our findings offer valuable insights into lung adenocarcinoma heterogeneity, suggesting avenues for targeted therapies in early-stage disease.

Risk factors and a prognostic model for patients with borderline resectable locally advanced T3-4N0-1 non-small cell lung cancer: a population-based study.

Background: Non-small cell lung cancer (NSCLC) is a malignant disease with a significant morbidity rate. For patients diagnosed with borderline resectable locally advanced (T3-4 invasion and N0-1) NSCLC, the optimal treatment and prognosis are still under debate. This study aimed to develop a predictive nomogram that could assess the prognosis of these patients and optimize clinical decision-making. Methods: Between 2010 to 2015, the survival, demographic and clinical characteristics of patients with borderline resectable locally advanced T3-4N0-1 NSCLC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Cox proportional hazard regression analyses were conducted to identify potential factors, which were further utilized to develop a dynamic nomogram for personalized prediction. Internal and external validation were conducted to verify the predictive accuracy of the nomogram. Results: Totally, 5,054 eligible records were enrolled into the study cohort. The included patients were divided into a training cohort (n=3,538) and a validation cohort (n=1,516) in a 7:3 ratio. Nine independent prognostic factors (including age, gender, primary site, lymph node removal, differentiation grade, T stage, N stage, histology and adjuvant chemotherapy) were finally included into the nomogram. The developed nomogram exhibited favorable discriminative ability with the C-index =0.71. Moreover, the calibration curves demonstrated excellent agreement between predicted and observed outcomes in both the training and validation cohorts. Notably, subgroup analyses revealed that neoadjuvant chemotherapy was significantly associated with a better overall survival (OS) (P<0.05) in patients staged as T3-4N1. Conclusions: In this study, we developed and validated a prognostic model to assist in clinical decision-making for patients with borderline resectable locally advanced T3-4N0-1 NSCLC. Our findings suggested that patients with T3-4N1 stage disease may derive significant benefits from neoadjuvant chemotherapy.

Causal relationship between gastro-esophageal reflux disease and risk of lung cancer: insights from multivariable Mendelian randomization and mediation analysis.

AIM: A recent study has reported that anti-reflux surgery reduced the risk of lung cancer. However, the exact causal association between gastro-esophageal reflux disease (GORD) and lung cancer remains obscure. Therefore, we conducted a multivariable and network Mendelian randomization (MR) study to explore this potential association and mediation effect. METHODS: Independent single nucleotide polymorphisms (SNPs) strongly associated with GORD were selected as instrumental variables (IVs) from the corresponding genome-wide association studies (GWAS). The summary statistics were obtained from the largest GORD GWAS meta-analysis of 367 441 (78 707 cases) European individuals, and the summary statistics of lung cancer and pathological subtypes came from International Lung Cancer Consortium (ILCCO) and FinnGen databases. Univariable and multivariable MR analyses were performed to investigate and verify the causal relationship between genetically predicted GORD and lung cancer. Network MR analysis was conducted to reveal the mediating role of GORD between smoking initiation and lung cancer. RESULTS: The univariable MR analysis demonstrated that GORD was associated with an increased risk of total lung cancer in both ILCCO [inverse variance weighted (IVW): odds ratio (OR) = 1.37, 95% confidence interval (CI) 1.16-1.62, P = 1.70E-04] and FinnGen database (IVW: OR = 1.25, 95% confidence interval CI 1.03-1.52, P = 2.27E-02). The consistent results were observed after adjusting the potential confounders [smoking traits, body mass index (BMI) and type 2 diabetes] in multivariable MR analyses. In subtype analyses, GORD was associated with lung adenocarcinoma (IVW: OR = 1.27, 95% CI 1.02-1.59, P = 3.48E-02) and lung squamous cell carcinomas (IVW: OR = 1.50, 95% CI 1.22-1.86, P = 1.52E-04). Moreover, GORD mediated 32.43% (95% CI 14.18-49.82%) and 25.00% (95% CI 3.13-50.00%) of the smoking initiation effects on lung cancer risk in the ILCCO and FinnGen databases, respectively. CONCLUSION: This study provides credible evidence that genetically predicted GORD was significantly associated with an increased risk of total lung cancer, lung adenocarcinoma and lung squamous cell carcinomas. Furthermore, our results suggest GORD is involved in the mechanism of smoking initiation-induced lung cancer.

Targeting cancer-related inflammation with non-steroidal anti-inflammatory drugs: Perspectives in pharmacogenomics.

Inflammatory processes are essential for innate immunity and contribute to carcinogenesis in various malignancies, such as colorectal cancer, esophageal cancer and lung cancer. Pharmacotherapies targeting inflammation have the potential to reduce the risk of carcinogenesis and improve therapeutic efficacy of existing anti-cancer treatment. Non-steroidal anti-inflammatory drugs (NSAIDs), comprising a variety of structurally different chemicals that can inhibit cyclooxygenase (COX) enzymes and other COX-independent pathways, are originally used to treat inflammatory diseases, but their preventive and therapeutic potential for cancers have also attracted researchers' attention. Pharmacogenomic variability, including distinct genetic characteristics among different patients, can significantly affect pharmacokinetics and effectiveness of NSAIDs, which might determine the preventive or therapeutic success for cancer patients. Hence, a more comprehensive understanding in pharmacogenomic characteristics of NSAIDs and cancer-related inflammation would provide new insights into this appealing strategy. In this review, the up-to-date advances in clinical and experimental researches targeting cancer-related inflammation with NSAIDs are presented, and the potential of pharmacogenomics are discussed as well.

Does surgical margin affect recurrence and survival after sublobar pulmonary resection for lung cancer?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: How does surgical margin distance affect recurrence and survival after sublobar pulmonary resection for lung cancer? Altogether, 172 papers were found using the search strategy, of which 12 studies with 1946 stage I non-small-cell lung cancer (NSCLC) patients using sublobar resection (wedge resection or segmentectomy) represented to be the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. Overall, 11 cohort studies and 1 prospective study were included. Four cohort studies demonstrated positive prognostic significance of surgical margin with specific cut-off points in each paper (ranged from 9 to 15 mm). Two retrospective studies and 1 prospective study found that a margin-to-tumour ratio of ≥1 was associated with better cytology and prognosis results. Other 5 studies showed that larger margin distance provided a favourable prognosis for NSCLC patients with poor-prognostic factors, including solid-dominant type, high invasive component size and Spread through Air Spaces-positive subtype. After reviewing all the included articles, we conclude that the standard of margin distance of >10 mm or margin-to-tumour ratio ≥ 1 should be recommended for stage I NSCLC patients undergoing sublobar resection, especially in wedge resection. Patients with poor-prognostic factors like solid-predominant tumour or non-lepidic adenocarcinoma may benefit from larger margin distance and the proper margin distance for them still needs to be determined. For Spread through Air Spaces-positive patients, sublobar resection may not be the alternative to lobectomy.

Whole-body vibration training - better care for COPD patients: a systematic review and meta-analysis.

PURPOSE: Whole-body vibrating training (WBVT) is a modality aiming to improve neuromuscular performance of patients with COPD. However, a consensus on the effects of WBVT has not been reached. We aimed to clarify the effects of WBVT on functional exercise capacity, pulmonary function, and quality of life in COPD patients. PATIENTS AND METHODS: PubMed, Web of Science, and EMBASE were searched through April 5, 2018. We calculated the pooled weight mean difference (WMD) using a random-effects model. Quality assessment and publication bias analyses were also performed. RESULTS: We included eight randomized control trials involving 365 patients. Compared with control group, WBVT increased 6-minute walking distance (6-MWD) (WMD: 62.14 m; 95% CI: 48.12-76.16; P<0.001), the change of 6-MWD (Δ6-MWD) (WMD: 42.33 m; 95% CI: 15.21-69.45; P=0.002), the change of the time to finish five repeated sit-to-stand tests (WMD: -2.07 seconds; 95% CI: -4.00 to -0.05; P=0.04), and decreased the change of St George's Respiratory Questionnaire score (WMD: -6.65 points; 95% CI: -10.52 to -2.78; P<0.001). However, no significant difference was found between the two groups regarding forced expired volume in 1 second (FEV1) (% predicated), change of FEV1 (% predicated), sit-to-stand test, 6-MWD (% predicated), change of 6-MWD (% predicated), St George's Respiratory Questionnaire score, COPD Assessment Test score, and change of COPD Assessment Test score. CONCLUSION: WBVT has beneficial effects on functional exercise capacity for COPD patients.

[Research Progress in the Therapeutic Strategy Based on Targeting at 
Lung Cancer Stem Cell].

With high morbidity and mortality, lung cancer is a major threat to human health and one of the focuses of tumor researches. Lung cancer stem cells (LCSCs) are regarded as a subpopulation of cells within lung cancer tissues with the capacity of self-renewal and differentiation, and might be related to tumorigenesis and heterogeneity of lung cancer. Tumor recurrence, metastasis and drug resistance of lung cancers could be clarified by LCSC hypothesis. Thus it's therapeutically prospective to target at these cells. This review summarizes the biomarkers of LCSCs and their aberrant signal pathways, as well as the therapeutic strategies targeting at LCSCs.