Lung adenocarcinomas (LUAD) arise from precancerous lesions such as atypical adenomatous hyperplasia, which progress into adenocarcinoma in situ and minimally invasive adenocarcinoma, then finally into invasive adenocarcinoma. The cellular heterogeneity and molecular events underlying this stepwise progression remain unclear. In this study, we perform single-cell RNA sequencing of 268,471 cells collected from 25 patients in four histologic stages of LUAD and compare them to normal cell types. We detect a group of cells closely resembling alveolar type 2 cells (AT2) that emerged during atypical adenomatous hyperplasia and whose transcriptional profile began to diverge from that of AT2 cells as LUAD progressed, taking on feature characteristic of stem-like cells. We identify genes related to energy metabolism and ribosome synthesis that are upregulated in early stages of LUAD and may promote progression. MDK and TIMP1 could be potential biomarkers for understanding LUAD pathogenesis. Our work shed light on the underlying transcriptional signatures of distinct histologic stages of LUAD progression and our findings may facilitate early diagnosis.

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BackgroundEnhanced recovery after surgery (ERAS) program is an effective evidence-based multidisciplinary protocol of perioperative care, but its roles in thoracic surgery remain unclear. This systematic review of randomized controlled trials (RCTs) aims to investigate the efficacy and safety of the ERAS programs for lung cancer surgery.Materials and methodsWe searched the PubMed and EMBASE databases to identify the RCTs that implemented an ERAS program encompassing more than four care elements within at least two phases of perioperative care in lung cancer surgery. The heterogeneity levels between studies were estimated by the Cochrane Collaborations. A qualitative review was performed if considerable heterogeneity was revealed. Relative risk (RR) and weighted mean difference served as the summarized statistics for the meta-analyses. Additional analyses were also performed to perceive potential bias risks.ResultsA total of seven RCTs enrolling 486 patients were included. The meta-analysis indicated that the ERAS group patients had significantly lower morbidity rates (RR=0.64; p<0.001), especially the rates of pulmonary (RR=0.43; p<0.001) and surgical complications (RR=0.46; p=0.010), than those of control group patients. No significant reduction was found in the in-hospital mortality (RR=0.70; p=0.58) or cardiovascular complications (RR=1.46; p=0.25). In the qualitative review, most of the evidence reported significantly shortened length of hospital and intensive care unit stay and decreased hospitalization costs in the ERAS-treated patients. No significant publication bias was detected in the meta-analyses.ConclusionOur review demonstrates that the implementation of an ERAS program for lung cancer surgery can effectively accelerate postoperative recovery and save hospitalization costs without compromising patients’ safety. A worldwide consensus guideline is urgently required to standardize the ERAS protocols for elective lung resections in the future.

Background: The objective of this study is to explore the association between the pretreatment systemic immune-inflammation index (SII) and prognosis in non-small cell lung cancer (NSCLC) patients.Methods: A systemic literature search of PubMed, EMBASE, the Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, VIP and SinoMed databases was performed from January 1, 1966 to April 15, 2019, to identify potential studies that assessed the prognostic role of the pretreatment SII in NSCLC. The hazard ratio (HR) and 95% confidence interval (CI) were combined to evaluate the correlation of the pretreatment SII with overall survival (OS), disease-free survival (DFS), progression-free survival (PFS) and cancer-specific survival (CSS) in NSCLC patients.Results: A total of 9 studies involving 2,441 patients were eventually included. An elevated pretreatment SII indicated significantly poorer OS (HR =1.88, 95% CI: 1.50-2.36; P<0.001) with high heterogeneity (I 2 =60.6%, P=0.019), DFS/PFS (HR =2.50, 95% CI: 1.20-5.20; P=0.014) with high heterogeneity (I 2 =58.2%, P=0.092) and CSS (HR =1.852, 95% CI: 1.185-2.915; P=0.007). Subgroup analyses further verified the above results. In addition, compared with the neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR), the SII showed a much higher prognostic value in NSCLC. Conclusions:The pretreatment SII may serve as a useful prognostic indicator in NSCLC and contribute to prognosis evaluation and treatment strategy formulation. However, more well-designed studies are warranted to verify our findings.

Non‐small‐cell lung cancer (NSCLC) has been recognized as a highly heterogeneous disease with phenotypic and genotypic diversity in each subgroup. While never‐smoker patients with NSCLC have been well studied through next generation sequencing, we have yet to recognize the potentially unique molecular features of young never‐smoker patients with NSCLC. In this study, we conducted whole genome sequencing (WGS) to characterize the genomic alterations of 36 never‐smoker Chinese patients, who were diagnosed with lung adenocarcinoma (LUAD) at 45 years or younger. Besides the well‐known gene mutations (e.g., TP53 and EGFR), our study identified several potential lung cancer‐associated gene mutations that were rarely reported (e.g., HOXA4 and MST1). The lung cancer‐related copy number variations (e.g., EGFR and CDKN2A) were enriched in our cohort (41.7%, 15/36) and the lung cancer‐related structural variations (e.g., EML4‐ALK and KIF5B‐RET) were commonly observed (22.2%, 8/36). Notably, new fusion partners of ALK (SMG6‐ALK) and RET (JMJD1C‐RET) were found. Furthermore, we observed a high prevalence (63.9%, 23/36) of potentially targetable genomic alterations in our cohort. Finally, we identified germline mutations in BPIFB1 (rs6141383, p.V284M), CHD4 (rs74790047, p.D140E), PARP1 (rs3219145, p.K940R), NUDT1 (rs4866, p.V83M), RAD52 (rs4987207, p.S346*), and MFI2 (rs17129219, p.A559T) were significantly enriched in the young never‐smoker patients with LUAD when compared with the in‐house noncancer database (p < 0.05). Our study provides a detailed mutational portrait of LUAD occurring in young never‐smokers and gives insights into the molecular pathogenesis of this distinct subgroup of NSCLC.

Caveolin-1 (Cav-1) is found predominately in terminally differentiated cells, such as adipocytes, endothelia and smooth muscle cells, as well as type I pneumocytes. As a main structural component of caveolae, Cav-1 is important in modulating cellular signaling. In the present study, the expression and clinical role of Cav-1 were analyzed in tumor stromal and human cancer cells, respectively. The results of previous studies have shown that the downregulation of tumor stromal Cav-1 promotes tumor survival and predicts a poor tumor prognosis, predominantly concentrating on the mechanism of the metabolism of the cancer microenvironment (according to the autophagic tumor stroma model of cancer metabolism and the reverse Warburg effect). However, contradictory results concerning the expression, clinical roles and associated mechanisms of Cav-1 have been reported. An improved understanding of Cav-1 expression in tumor stromal and cancer cells will increase knowledge with regard to the clinical value of Cav-1 and its detailed mechanisms. This review summarizes the novel data concerning the clinical values and probable mechanisms of Cav-1 expression in tumor stromal (predominantly in cancer-associated fibroblasts) and cancer cells, respectively.

BackgroundAn evaluation of cardiopulmonary exercise testing (CPET) screening and pre-operative pulmonary rehabilitation in reducing postoperative complications and improving fast-track recovery in high-risk patients who undergo resection for lung cancer.MethodsOf 342 potential lung cancer cases, 142 high-risk patients were finally divided into two groups: group R (n = 71) underwent an intensive pre-operative pulmonary rehabilitation program (PRP), followed by lobectomy; group S (n = 71) underwent only lobectomy with conventional management. Postoperative complications, average days in hospital, postoperative days in hospital, and cost were analyzed.ResultsThe 142 high-risk patients were screened by smoking history and CPET. Sixty-eight patients had bronchial hyperresponsiveness (BHR) and 47 patients had peak expiratory flow <250 L/minute by CPET. The rate of postoperative total complications in group R (16.90%) was significantly lower than in group S (83.31%) (P = 0.00), as was the rate of postoperative pulmonary complications PPC: group R (12.81%) versus S (13.55%) (P = 0.009); the PPC in the left lung (17.9%) was higher than in the right lung (2.3%) (P = 0.00). The average days in hospital in group S was significantly higher than in group R (P = 0.03). There was no difference between groups in average hospital cost (P = 0.304).ConclusionPre-operative screening using CPET is conducive to identifying high-risk patients for lung resection. Pre-operative pulmonary rehabilitation is helpful to reduce postoperative complications and improve fast-track recovery.

Background Lung cancer is the most important cause of cancer-related deaths worldwide and the overall survival of patients with non-small cell lung cancer has not improved. Transforming growth factor beta or TGF-β is a polypeptide member of the transforming growth factor beta superfamily of cytokines, while far fewer clinical studies addressing the association between TGF-β expression and the disease prognosis have been reported up to now. Therefore, our meta-analysis aims to determine the prognostic significance of TGF-β expression in lung cancer patients. Methods PubMed, EMBASE, the Web of Science and China National Knowledge Infrastructure (CNKI) databases were searched for full-text literature citations. We applied the hazard ratio (HR) with 95% confidence interval (CI) as the appropriate summarized statistics. Q-test and I 2 statistic were used to estimate the level of heterogeneity. The publication bias was detected by Begg’s test and Egger’s test. Results Eight eligible studies involving 579 patients were selected for this meta-analysis. The combined HR for the eight eligible studies was 2.17 (95% CI: 1.71–2.77, P < 0.00001) and heterogeneity of overall prognosis was relatively low (I 2 = 14.2%, P = 0.319). We further undertook the subgroup analysis including assessment of the association between TGF-β expression and pathology of the lung cancer, treatment and quantity of sample in studies. All the results revealed that a significantly high TGF-β expression in patients was an indicator of poor survival. Neither Begg’s test nor Egger’s test found publication bias in any analysis. Conclusions The present evidence indicates that TGF-β expression can significantly predict the worse prognosis in patients with lung cancer. The findings of our meta-analysis may be confirmed in the future by the use of more updated review pooling and additional relevant investigations.