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.
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.
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