Lung cancer is a highly heterogeneous disease. Cancer cells and cells within the tumor microenvironment together determine disease progression, as well as response to or escape from treatment. To map the cell type-specific transcriptome landscape of cancer cells and their tumor microenvironment in advanced non-small cell lung cancer (NSCLC), we analyze 42 tissue biopsy samples from stage III/IV NSCLC patients by single cell RNA sequencing and present the large scale, single cell resolution profiles of advanced NSCLCs. In addition to cell types described in previous single cell studies of early stage lung cancer, we are able to identify rare cell types in tumors such as follicular dendritic cells and T helper 17 cells. Tumors from different patients display large heterogeneity in cellular composition, chromosomal structure, developmental trajectory, intercellular signaling network and phenotype dominance. Our study also reveals a correlation of tumor heterogeneity with tumor associated neutrophils, which might help to shed light on their function in NSCLC.

N 6-methyladenosine (m 6 A) is the most prevalent internal RNA modification in mammals that regulates homeostasis and function of modified RNA transcripts. Here we aimed to investigate the role of YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), a key regulator of m 6 A methylation in gastric cancer (GC) tumorigenesis. Multiple bioinformatic analyses of different human cancer databases identified key m 6 A-associated genetic mutations that regulated gastric tumorigenesis. YTHDF1 was mutated in about 7% of gastric cancer patients and high expression of YTHDF1 was associated with more aggressive tumor progression and poor overall survival. Inhibition of YTHDF1 attenuated GC cell proliferation and tumorigenesis in vitro and in vivo. Mechanistically, YTHDF1 promoted the translation of a key Wnt receptor frizzled7 (FZD7) in an m 6 A-dependent manner, and mutated YTHDF1 enhanced expression of FZD7, leading to hyper-activation of the Wnt/β-catenin pathway and promotion of gastric carcinogenesis. Our results demonstrate the oncogenic role of YTHDF1 and its m 6 A-mediated regulation of Wnt/β-catenin signaling in gastric cancer, providing a novel approach of targeting such epigenetic regulators in this disease. Research.

Background/objectivesThe assessment of nutritional status and the quality of life in patients with gastric cancer has become one of the important goals of current clinical treatment. The purpose of this study was to assess the nutritional status in hospitalized gastric cancer patients by using patient-generated subjective global assessment (PG-SGA) and to analyze the influence of nutritional status on the patients’ quality of life (QOL).MethodsWe reviewed the pathological diagnosis of gastric cancer for 2322 hospitalized patients using PG-SGA to assess their nutritional status and collected data on clinical symptoms, the anthropometric parameters (height, weight, body mass index (BMI), mid-arm circumference (MAC), triceps skin-fold thickness (TSF), and hand-grip strength (HGS). We also collected laboratory data (prealbumin, albumin, hemoglobin) within 48 h after the patient was admitted to the hospital. The 30-item European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) was used for QOL assessment in all patients.ResultsBy using PG-SGA, we found 80.4% of the patients were malnourished (score ≥ 4) and 45.1% of the patients required urgent nutritional support (score ≥ 9). In univariate analysis, old age (> 65 years, p < 0.001), female (p = 0.007), residence in a village (p = 0.004), a lower level of education (p < 0.001), and self-paying (p < 0.001) were indicated as risk factors of patients with gastric cancer to be suffering from severe malnutrition. There was a negative correlation between PG-SGA and various nutritional parameters (p < 0.05). The quality of life was significantly different in gastric cancer patients with different nutritional status (p < 0.01).ConclusionMalnutrition of hospitalized patients with gastric cancer in China is common and seriously affects the patients’ quality of life. The nutritional status should be evaluated in a timely manner and reasonable nutritional intervention should be provided as soon as possible. The PG-SGA was fit for using as a clinical nutrition assessment method, being worthy of clinical application.