Tislelizumab combined with nab-paclitaxel and cisplatin as the more effective chemoimmunotherapy strategy in the neoadjuvant treatment of locally advanced thoracic esophageal squamous cell carcinoma: A prospective, two-cohort, phase 2 trial.

This prospective, two-cohort phase 2 trial with random allocation was conducted to evaluate the safety and efficacy of neoadjuvant tislelizumab combined with nab-paclitaxel/paclitaxel and cisplatin (TP) in patients with esophageal squamous cell carcinoma (ESCC). Patients were enrolled and randomly assigned to the nab-paclitaxel or paclitaxel cohorts at a 1:1 ratio, and received intravenous tislelizumab (200 mg, day 1) combined with cisplatin (25 mg/m, days 1-3) and either nab-paclitaxel (125 mg/m, days 1 and 8) or paclitaxel (150 mg/m, day 1) in a 21-day cycle for two cycles before surgery. The primary endpoint was the major pathological response (MPR) rate.

Hydrogen sulfide improved learning and memory deficits by reversing the inhibition of methylmercuric chloride on BDNF/TrkB signaling pathway.

Objective: Methylmercuric chloride (MMC) has neurotoxicity, while hydrogen sulfide (H2S) has shown inhibitory properties against nerve damage induced by various factors. The study aimed to investigate the impact of H2S on MMC-induced learning and memory impairment in mice and to explore the underlying mechanisms.

Methods: A mouse model of learning and memory impairment was established by MMC gavage, and sodium hydrosulfide (NaHS) was used as an H2S donor for intervention.

Extent of surgical resection for radiologically subsolid T1N0 invasive lung adenocarcinoma: When is a wedge resection acceptable?

Objective: To evaluate whether wedge resection (WR) was appropriate for the patients with peripheral T1 N0 solitary subsolid invasive lung adenocarcinoma.

Methods: Patients with peripheral T1N0 solitary subsolid invasive lung adenocarcinoma who received sublobar resection were retrospectively reviewed. Clinicopathologic characteristics, 5-year recurrence-free survival, and 5-year lung cancer-specific overall survival were analyzed.

Counteracting lineage-specific transcription factor network finely tunes lung adeno-to-squamous transdifferentiation through remodeling tumor immune microenvironment.

Human lung adenosquamous cell carcinoma (LUAS), containing both adenomatous and squamous pathologies, harbors strong plasticity and is significantly associated with poor prognosis. We established an up-to-date comprehensive genomic and transcriptomic landscape of LUAS in 109 Chinese specimens and demonstrated LUAS development via adeno-to-squamous transdifferentiation. Unsupervised transcriptomic clustering and dynamic network biomarker analysis identified an inflammatory subtype as the critical transition stage during LUAS development.

RBM10 Loss Promotes EGFR-Driven Lung Cancer and Confers Sensitivity to Spliceosome Inhibition.

Unlabelled: In lung adenocarcinoma (LUAD), loss-of-function mutations in the splicing factor RBM10 frequently co-occur with oncogenic EGFR mutations. A detailed understanding of the functional consequences and therapeutic impact of RBM10 loss in EGFR-mutant LUAD could help identify more effective treatment strategies. Here, analysis of LUAD data sets indicated that RBM10 mutations are mutually exclusive with mutations in the tumor suppressor gene TP53.

Oxidative stress-triggered Wnt signaling perturbation characterizes the tipping point of lung adeno-to-squamous transdifferentiation.

Lkb1 deficiency confers the Kras-mutant lung cancer with strong plasticity and the potential for adeno-to-squamous transdifferentiation (AST). However, it remains largely unknown how Lkb1 deficiency dynamically regulates AST. Using the classical AST mouse model (Kras ;Lkb1, KL), we here comprehensively analyze the temporal transcriptomic dynamics of lung tumors at different stages by dynamic network biomarker (DNB) and identify the tipping point at which the Wnt signaling is abruptly suppressed by the excessive accumulation of reactive oxygen species (ROS) through its downstream effector FOXO3A.

Efficacy and safety of neoadjuvant chemotherapy and immunotherapy in locally resectable advanced esophageal squamous cell carcinoma.

Background: Esophageal squamous cell cancer (ESCC) patients with the potentially resectable disease most would experience relapse after surgery. Immunotherapy has been reported to improve the prognosis of advanced esophageal cancer and may be a new strategy to prevent this urgent condition's recurrence. We first evaluated the efficacy and safety of neoadjuvant chemotherapy combined with immunotherapy in patients with resectable ESCC.

Is flexible bronchoscopy necessary in the preoperative workup of patients with peripheral cT1N0 subsolid lung cancer? -a prospective multi-center cohort study.

Background: Necessity of flexible bronchoscopy (FB) examination as a routine preoperative work-up for peripheral clinical T1N0 subsolid lung cancer was unknown.

Methods: This was a prospective, multi-center clinical trial (NCT03591445). Patients with peripheral GGO nodules (GGNs) who were candidates for surgical resection were enrolled.

A systematic dissection of the epigenomic heterogeneity of lung adenocarcinoma reveals two different subclasses with distinct prognosis and core regulatory networks.

Background: Lung adenocarcinoma (LUAD) is a highly malignant and heterogeneous tumor that involves various oncogenic genetic alterations. Epigenetic processes play important roles in lung cancer development. However, the variation in enhancer and super-enhancer landscapes of LUAD patients remains largely unknown.

Preoperative Folate Receptor-Positive Circulating Tumor Cell Level Is a Prognostic Factor of Long Term Outcome in Non-Small Cell Lung Cancer Patients.

Background: Surgical resection is often the preferred treatment for non-small cell lung cancer (NSCLC) patients. Predictive biomarkers after surgery can help monitoring and treating patients promptly, so as to improve the clinical outcome. In this study, we evaluated one potential candidate biomarker, the folate receptor-positive circulating tumor cell (FRCTC), by investigating its prognostic and predictive significance in NSCLC patients who underwent surgery.

Esophagectomy With Three-Field Versus Two-Field Lymphadenectomy for Middle and Lower Thoracic Esophageal Cancer: Long-Term Outcomes of a Randomized Clinical Trial.

Introduction: The optimal extent of lymphadenectomy during esophagectomy remains unclear. In this trial, we aim to clarify whether three-field (cervical-thoracic-abdominal) lymphadenectomy improved patient survival over two-field (thoracic-abdominal) lymphadenectomy for esophageal cancer.

Methods: Between March 2013 and November 2016, a total of 400 patients with middle and lower thoracic esophageal cancer were included and randomly assigned to undergo esophagectomy with either three- or two-field lymphadenectomy at a 1:1 ratio.

RNA binding motif protein 10 suppresses lung cancer progression by controlling alternative splicing of eukaryotic translation initiation factor 4H.

Background: RNA splicing defects are emerging molecular hallmarks of cancer. The gene encoding splicing factor RNA binding motif protein 10 (RBM10) has been found frequently mutated in various types of cancer, particularly lung adenocarcinoma (LUAD), but how RBM10 affects cancer pathogenesis remains to be determined. Moreover, the functional roles and clinical significance of RBM10 mutation-associated splicing events in LUAD are largely unknown.

SMYD3 overexpression indicates poor prognosis and promotes cell proliferation, migration and invasion in non‑small cell lung cancer.

SET and MYND domain‑containing protein 3 (SMYD3) is a lysine methyltransferase, and its aberrant expression has been implicated in several malignancies. However, its clinical and biological roles in non‑small cell lung cancer (NSCLC) remain unclear. In the present study, it was revealed that SMYD3 was significantly upregulated in NSCLC tissues, as compared with paired adjacent normal tissues.

EGFR-mutant lung adenocarcinoma harboring co-mutational tumor suppressor genes predicts poor prognosis.

Introduction: EGFR mutations occur most frequently in patients with lung adenocarcinoma in East Asia. However, the prognostic and therapeutic impact of co-mutational status of EGFR and tumor suppressor genes is not fully understood. This study aims to provide a deeper understanding of lung adenocarcinoma patients with co-mutation of EGFR and tumor suppressor genes.

Correlation between PD-L1 expression and clinicopathological characteristics of non-small cell lung cancer: A real-world study of a large Chinese cohort.

Background: Programmed death ligand-1 (PD-L1) is a predictive marker of anti-programmed death protein 1 (PD-1)/PD-L1 therapies for non-small cell lung cancer (NSCLC). However, little is known between PD-L1 expression and the clinicopathological characteristics of NSCLC in the Chinese population in a real-world setting.

Methods: We analyzed PD-L1 expression by immunohistochemistry (IHC) in NSCLC patients using the 22C3 clone on the Dako Autostainer Link 48 platform.

Imaging Features Suggestive of Multiple Primary Lung Adenocarcinomas.

Background: The tumor-node-metastasis classification system has proposed that lung cancers presenting as multifocal ground-glass nodules (multi-GGN) on computed tomography scan should be staged as multiple primaries instead of intrapulmonary metastases. However, the problem still exists for those synchronous multiple lung adenocarcinomas (SMLA) involving solid lesions. This study aimed to explore the distinct features of SMLA to better define the diagnosis and staging of this disease.

Genomic and immune profiling of pre-invasive lung adenocarcinoma.

Adenocarcinoma in situ and minimally invasive adenocarcinoma are the pre-invasive forms of lung adenocarcinoma. The genomic and immune profiles of these lesions are poorly understood. Here we report exome and transcriptome sequencing of 98 lung adenocarcinoma precursor lesions and 99 invasive adenocarcinomas.

Detection of Novel NRG1, EGFR, and MET Fusions in Lung Adenocarcinomas in the Chinese Population.

Introduction: Multiple oncogene fusions beyond ALK receptor tyrosine kinase (ALK), RET, and ROS1 fusion has been described in lung cancer, especially in lung adenocarcinomas without common oncogenic mutations. Molecular inhibitors have been developed and proved effective for patients whose tumors harbor these novel alterations.

Methods: A consecutive series of surgically resected lung adenocarcinomas were collected and profiled using an enrichment strategy to detect nine common oncogenic driver mutations and fusions concerning EGFR, KRAS, HER2, BRAF, MET, ALK, RET, ROS1, and FGFR.

Outcomes comparison between neoadjuvant chemotherapy and adjuvant chemotherapy in stage IIIA non-small cell lung cancer patients.

Background: A neoadjuvant chemotherapy (NCT) is a feasible second-option other than an adjuvant chemotherapy (ACT); however, no definite conclusions have been drawn about whether or not a NCT is associated with better clinical outcomes for IIIA non-small cell lung cancer (NSCLC) patients.

Methods: We reviewed 68 clinical IIIA NSCLC patients who received preoperative chemotherapy (NCT group), and 535 pathological IIIA NSCLC patients who received ACT after surgery (ACT group). After a 1:1 propensity score matching (PSM), we compared the relapse-free survival (RFS) and overall survival (OS) rates as the long-term clinical outcomes, and hospital stay, surgery duration, postoperative complications as the short-term clinical outcomes.

tRNA-based prognostic score in predicting survival outcomes of lung adenocarcinomas.

As the most abundant noncoding RNA in cells, tRNA plays an important role in tumorigenesis and development. The report of tRNA on the pathogenesis of lung adenocarcinoma is rare. It is of great clinical significance to explore the relationship between tRNA expression and prognosis of lung adenocarcinoma.

Comparative analysis of co-occurring mutations of specific tumor suppressor genes in lung adenocarcinoma between Asian and Caucasian populations.

Introduction: Mutated tumor suppressor genes (TSG) such as TP53, STK11, and MGA are widely-reported. We hypothesized the presence of single mutation or co-occurring mutations in these specific genes may represent a significant therapeutic target for lung adenocarcinoma.

Methods: We sequenced lung adenocarcinoma samples from 677 East-Asian patients, combined them with those from cBioPortal public database (including TCGA) and performed a comparative analysis between Asian and Caucasian populations.

The lymph node status and histologic subtypes influenced the effect of postoperative radiotherapy on patients with N2 positive IIIA non-small cell lung cancer.

Background And Objective: To investigate the role of postoperative radiotherapy (PORT) in IIIA-N2 non-small cell lung cancer (NSCLC) patients and subgroups which derived benefit from PORT.

Methods: A total of 576 patients with pathological IIIA-N2 NSCLC, who underwent complete resection, were identified. Propensity score matching (PSM) methods were used to balance the patients' characteristics between two groups.

Frequency and clinical significance of NF1 mutation in lung adenocarcinomas from East Asian patients.

NF1 is a tumor suppressor gene that negatively regulates Ras signaling. NF1 deficiency plays an important role in carcinogenesis. To investigate the frequency and clinical significance of NF1 mutation, we examined mutation status of NF1, TP53, LKB1 and RB1 in 704 surgically resected lung adenocarcinomas from East Asian patients using semiconductor-based Ion Torrent sequencing platform.