Proteogenomic characterization reveals tumorigenesis and progression of lung cancer manifested as subsolid nodules.

Lung adenocarcinoma (LUAD) radiologically displayed as subsolid nodules (SSNs) is prevalent. Nevertheless, the precise clinical management of SSNs necessitates a profound understanding of their tumorigenesis and progression. Here, we analyze 66 LUAD displayed as SSNs covering 3 histological stages including adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) by incorporating genomics, proteomics, phosphoproteomics and glycoproteomics.

Neuronal guanine nucleotide exchange factor promotes the axonal growth and cancer cell proliferation via Ephrin-A3/EphA2 axis in lung adenocarcinoma.

Background: Neural infiltration has been found in various cancers and the infiltrating nerves influence tumor growth and dissemination. In non-small cell lung cancer, pan-neuronal marker PGP9.5 was detected by immunohistochemical staining and its high expression correlated with poor prognosis.

An update on small molecule compounds targeting synthetic lethality for cancer therapy.

Targeting cancer-specific vulnerabilities through synthetic lethality (SL) is an emerging paradigm in precision oncology. A SL strategy based on PARP inhibitors has demonstrated clinical efficacy. Advances in DNA damage response (DDR) uncover novel SL gene pairs.

Development and therapeutic perspectives of CXCR4 antagonists for disease therapy.

Chemokine receptor 4 (CXCR4) is a subtype receptor protein of the GPCR family with a seven-transmembrane structure widely distributed in human tissues. CXCR4 is involved in diseases (e.g.

An immune cell map of human lung adenocarcinoma development reveals an anti-tumoral role of the Tfh-dependent tertiary lymphoid structure.

The immune responses during the initiation and invasion stages of human lung adenocarcinoma (LUAD) development are largely unknown. Here, we generated a single-cell RNA sequencing map to decipher the immune dynamics during human LUAD development. We found that T follicular helper (Tfh)-like cells, germinal center B cells, and dysfunctional CD8 T cells increase during tumor initiation/invasion and form a tertiary lymphoid structure (TLS) inside the tumor.

A Highly Sensitive and Specific Non-Invasive Test through Genome-Wide 5-Hydroxymethylation Mapping for Early Detection of Lung Cancer.

Low-dose computed tomography screening can increase the detection for non-small-cell lung cancer (NSCLC). To improve the diagnostic accuracy of early-stage NSCLC detection, ultrasensitive methods are used to detect cell-free DNA (cfDNA) 5-hydroxymethylcytosine (5hmC) in plasma. Genome-wide 5hmC is profiled in 1990 cfDNA samples collected from patients with non-small cell lung cancer (NSCLC, n = 727), healthy controls (HEA, n = 1,092), as well as patients with small cell lung cancer (SCLC, n = 41), followed by sample randomization, differential analysis, feature selection, and modeling using a machine learning approach.

A bioengineered trachea-like structure improves survival in a rabbit tracheal defect model.

A practical strategy for engineering a trachea-like structure that could be used to repair or replace a damaged or injured trachea is an unmet need. Here, we fabricated bioengineered cartilage (BC) rings from three-dimensionally printed fibers of poly(ɛ-caprolactone) (PCL) and rabbit chondrocytes. The extracellular matrix (ECM) secreted by the chondrocytes combined with the PCL fibers formed a "concrete-rebar structure," with ECM deposited along the PCL fibers, forming a grid similar to that of native cartilage.

Validation of the Proposed International Association for the Study of Lung Cancer Residual Tumor Classification to Upgrade Extracapsular Extension of Tumor in Nodes From R0 to Incomplete Resection.

Introduction: The International Association for the Study of Lung Cancer (IASLC) proposed a revised R classification to upstage extracapsular extension (ECE) of tumor in nodes from R0 to R1. Nevertheless, evidence to confirm this proposal is insufficient.

Methods: The study included 4061 surgical patients with NSCLC.

Clinical utility of [F]FDG PET/CT in the assessment of mediastinal lymph node disease after neoadjuvant chemoimmunotherapy for non-small cell lung cancer.

Objectives: The performance of positron emission tomography/computed tomography (PET/CT) for the prediction of ypN2 disease in non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy has not been reported. This multicenter study investigated the utility of PET/CT to assess ypN2 disease in these patients.

Methods: A total of 181 consecutive patients (chemoimmunotherapy = 86, chemotherapy = 95) at four institutions were enrolled in this study.

Development of the semi-dry dot-blot method for intraoperative detecting micropapillary component in lung adenocarcinoma based on proteomics analysis.

Background: Micropapillary (MIP) component was a major concern in determining surgical strategy in lung adenocarcinoma (LUAD). We sought to develop a novel method for detecting MIP component during surgery.

Methods: Differentially expressed proteins between MIP-positive and MIP-negative LUAD were identified through proteomics analysis.

Pharmacological boosting of cGAS activation sensitizes chemotherapy by enhancing antitumor immunity.

Enhancing chemosensitivity is one of the largest unmet medical needs in cancer therapy. Cyclic GMP-AMP synthase (cGAS) connects genome instability caused by platinum-based chemotherapeutics to type I interferon (IFN) response. Here, by using a high-throughput small-molecule microarray-based screening of cGAS interacting compounds, we identify brivanib, known as a dual inhibitor of vascular endothelial growth factor receptor and fibroblast growth factor receptor, as a cGAS modulator.

The IASLC grading system for invasive pulmonary adenocarcinoma: a potential prognosticator for patients receiving neoadjuvant therapy.

Background: Grading system for resected invasive pulmonary adenocarcinoma proposed by the International Association for the Study of Lung Cancer (IASLC) was validated as a strong prognostic indicator. Nonetheless, the efficacy of utilizing such grading system in prognostic assessment of patients receiving neoadjuvant therapy still needs elucidating.

Methods: A retrospective study was conducted including patients with resected adenocarcinoma following neoadjuvant chemotherapy or targeted therapy from August 2012 to December 2020 in Shanghai Pulmonary Hospital.

Clinicopathologic characteristics and prognostic impact of atypical EGFR mutations in completely resected lung adenocarcinoma.

Introduction: This study evaluated the clinicopathologic characteristics and prognostic impact of atypical epidermal growth factor receptor (EGFR) mutations in patients with completely resected lung adenocarcinoma (LUAD) and investigate whether adjuvant chemotherapy could benefit the survival outcomes for these subjects.

Material And Methods: We retrospectively reviewed resected LUAD samples from 8437 patients and identified 5358 EGFR-mutated (EGFRm) cases. Of these, 4847 had classical mutations, while 511 had atypical mutations.

Characterization of the evolution trajectory and immune profiling of new histologic patterns in lung adenocarcinoma.

In lung adenocarcinoma (LUAD), the appearance of morphologically diverse tumor regions, termed histological patterns, is closely associated with disease progression and lymph node metastasis. However, the molecular characteristics of the histological patterns in LUAD and the underlying molecular evolutionary mechanisms between the histological patterns in primary tumors and lymph node metastases are poorly understood. Here, we re-analyzed the large TCGA-LUAD dataset and depicted a comprehensive profiling of the genome and transcriptome across the histological patterns in LUAD.

Development and validation of a deep learning model to predict the survival of patients in ICU.

Background: Patients in the intensive care unit (ICU) are often in critical condition and have a high mortality rate. Accurately predicting the survival probability of ICU patients is beneficial to timely care and prioritizing medical resources to improve the overall patient population survival. Models developed by deep learning (DL) algorithms show good performance on many models.

Prognostic evaluation of the proposed residual tumor classification in a Chinese non-small cell lung cancer population.

Background: This study aimed to validate the R classification including uncertain resection (R-un) proposed by the International Association for the Study of Lung Cancer (IASLC) in a Chinese non-small cell lung cancer (NSCLC) population.

Methods: The study retrospectively investigated a 2009-2013 single-institutional NSCLC resection cohort in China. After reclassification, recurrence-free survival (RFS) and overall survival (OS) were calculated using survival analyses and compared with those using the 2005 version IASLC R classification.

Deciphering the Immune-Tumor Interplay During Early-Stage Lung Cancer Development Single-Cell Technology.

Lung cancer is the leading cause of cancer-related death worldwide. Cancer immunotherapy has shown great success in treating advanced-stage lung cancer but has yet been used to treat early-stage lung cancer, mostly due to lack of understanding of the tumor immune microenvironment in early-stage lung cancer. The immune system could both constrain and promote tumorigenesis in a process termed immune editing that can be divided into three phases, namely, elimination, equilibrium, and escape.

Converging 3D Printing and Electrospinning: Effect of Poly(l-lactide)/Gelatin Based Short Nanofibers Aerogels on Tracheal Regeneration.

Recently, various tissue engineering based strategies have been pursued for the regeneration of tracheal tissues. However, previously developed tracheal scaffolds do not accurately mimic the microstructure and mechanical behavior of the native trachea, which restrict their clinical translation. Here, tracheal scaffolds are fabricated by using 3D printing and short nanofibers (SF) dispersion of poly(l-lactide)/gelatin (0.

Predicted outcomes of subdividing M1-stage metastatic lung cancer based on the prognosis and the response to local consolidative therapy.

Background: For stage IV non-small cell lung cancer (NSCLC) patients, systemic therapy is the main strategy, and local consolidative therapy tends to be performed for patients with oligometastases. The porpose of this article is to evaluate the prognostic effects of local consolidative therapy for patients with stage IV NSCLC and divide these patients into different subcategories to stratify the prognoses.

Methods: A total of 30,583 patients with stage IV NSCLC were identified in the Surveillance, Epidemiology, and End Results (SEER) database.

Morphological Subtypes of Tumor Spread Through Air Spaces in Non-Small Cell Lung Cancer: Prognostic Heterogeneity and Its Underlying Mechanism.

Background: Tumor spread through air spaces (STAS) has three morphologic subtypes: single cells, micropapillary clusters, and solid nests. However, whether their respective clinical significance is similar remains unclear.

Methods: We retrospectively reviewed 803 patients with resected non-small cell lung cancer (NSCLC) from January to December 2009.

Which N Descriptor Is More Predictive of Prognosis in Resected Non-small Cell Lung Cancer: The Number of Involved Nodal Stations or the Location-Based Pathological N Stage?

Background: The eighth edition of nodal classification for non-small cell lung cancer (NSCLC) is defined only by the anatomical location of metastatic lymph nodes.

Research Question: We sought to evaluate the prognostic significance and discriminatory capability of the number of involved nodal stations (nS) in a large Chinese cohort.

Study Design And Methods: A total of 4,011 patients with NSCLC undergoing surgical resection between 2009 and 2013 were identified.

Bayesian network meta-analysis of efficacy and safety of neoadjuvant therapy for non-small-cell lung cancer.

Objective: Neoadjuvant chemotherapy has increased the survival benefit of non-small cell lung cancer (NSCLC) patients. The effects of different neoadjuvant therapies are still controversial. We carried out the study to evaluate the efficacy and safety of neoadjuvant therapy.

Recognition of filigree pattern expands the concept of micropapillary subtype in patients with surgically resected lung adenocarcinoma.

Our study aimed to validate the clinicopathological characteristics and prognosis of lung adenocarcinoma (ADC) with a filigree pattern and to further investigate the relationship between the filigree pattern and the classical micropapillary (MP) pattern. We retrospectively reviewed the clinical and pathologic characteristics of 461 Chinese patients with completely resected ADC (stage I, 310; stage II, 44; stage III, 107). The filigree pattern was more likely to be observed in ADC with a higher stage (p = 0.