Correlation analysis of EGFR gene mutation abundance and the efficacy of targeted therapy with osimertinib in nonsmall cell lung cancer-a case control study.

BACKGROUND: In nonsmall cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) mutation is the primary cancer-causing mutation. But whether the practical effectiveness of EGFR tyrosine kinase inhibitors (TKIs) can be influenced by plasma EGFR mutation abundance when treating patients with advanced NSCLC remains unanswered. Therefore, this research was intended to reveal the connection between plasma EGFR mutation abundance and clinical outcomes in osimertinib-treated patients with advanced NSCLC. METHODS: A total of 120 patients with advanced NSCLC were retrospectively analyzed, and 56 patients with EGFR-mutation-positive NSCLC receiving osimertinib first-line therapy were eventually screened and included. The baseline status and abundance of plasma EGFR in patients with NSCLC were detected by cSMART, and the ratio of 0.1 was the critical value. Imaging examinations were performed every 8-12 weeks for the assessment of tumor response. The relationship between baseline EGFR mutation abundance and clinical outcomes of TKI therapy was analyzed. RESULTS: The objective response rates (ORR) of EGFR-mutant patients in the high-/low-abundance groups were 69.2% and 40.0%, respectively. The high abundance group had an obviously higher ORR than the low abundance group (P = 0.029). A much longer median progression-free survival (mPFS) was demonstrated in patients with high mutation abundance than in patients with low abundance (11.2 months vs 7.1 months, P = 0.0133). As for the median overall survival (mOS), it showed the same trend as mPFS in patients from different groups (15.5 vs 10.7 months, P = 0.0028). The role of plasma mutation abundance as an independent prognostic factor for both PFS (hazard ratios [HR]: 0.30, P = 0.006) and OS (HR: 0.35, P = 0.004) was demonstrated by multivariate Cox regression analysis. CONCLUSION: There is a close connection between plasma EGFR mutation abundance and survival benefit in patients with NSCLC, which can be used for predicting the efficacy of EGFR-TKI targeted therapy. Our study is expected to provide a research basis for screening patients to whom the EGFR-TKI therapy is beneficial.

Prognostic value of genes related to cancer-associated fibroblasts in lung adenocarcinoma.

BACKGROUND: Although it has been established that cancer-associated fibroblasts (CAFs) facilitate tumor development, the relationship between CAFs and the prognosis of patients with lung adenocarcinoma (LUAD) has not been extensively explored. OBJECTIVE: This study was formulated to investigate the prognostic value of CAF-related genes in LUAD. METHODS: Differential analysis was carried out with TCGA-LUAD dataset as the training set. By overlapping differentially expressed genes (DEGs) with genes associated with CAF, CAF-related DEGs specific to LUAD were obtained. A prognostic risk model was constructed by Lasso and Cox regression analysis, and samples were grouped according to median risk score. The efficacy of the model was accessed through survival curve and receiver operating characteristic curve (ROC) analyses, with the validation set for verification. Risk score combined with clinical factors was utilized for Cox analysis to verify the independence of the model, and a nomogram was drawn. GSEA was performed on different risk groups. Immunologic infiltration and tumor mutational burden were assessed in different risk groups. RESULTS: Eleven feature genes including DLGAP5, KCNE2, UPK2, NPAS2, ARHGAP11A, ANGPTL4, ANLN, DKK1, SMUG1, C16orf74, and ACAD8 were identified, based on which a prognostic model was constructed. Risk score could predict the prognosis of LUAD patients and could be an independent prognostic factor for LUAD patients. GSEA outcomes displayed significant enrichment of genes in the high-risk group in the P53 SIGNALING PATHWAY. In comparison to the low-risk group, the high-risk group exhibited a decreased degree of immune infiltration and an elevated level of tumor mutational burden. CONCLUSION: An 11-gene model was constructed based on CAF-related genes to predict LUAD prognosis. This model represented an independent prognostic factor for LUAD.

Establishment and characterization of a new gastric cancer cell line, XGC-1.

BACKGROUND: To establish a primary human gastric cancer cell line. METHODS: Fresh gastric cancer tissue samples were separated into a cell suspension, and DMEM/F12 medium containing 10% foetal bovine serum was used for primary culture and subculture. The morphology of the cells was observed under a light microscope, and the cell growth curve was plotted. A soft agar colony formation assay was used to detect the colony formation ability of the cell line. Immunohistochemical methods were used to detect cytokeratin, vimentin and Ki-67, the chromosome G banding method was used to analyse the karyotype of the cells, and the tumourigenic ability of the cells was detected by subcutaneous inoculation of BALB/C nude mice. RESULTS: We established a gastric cancer cell line from a 68-year-old male patient. This gastric cancer cell line was named XGC-1 and had a doubling time of approximately 48 h. The cell line displayed strong colony formation ability and tumourigenicity in BALB/C nude mice and had complicated chromosomal abnormalities. When nutrients were insufficient, the cells shed and floated in the medium, but adherent growth was observed in nutrient-rich conditions. CONCLUSIONS: The XGC-1 cell line will be useful for future studies of gastric cancer development, progression, metastasis and therapy.

Regulatory network of circRNA-miRNA-mRNA contributes to the histological classification and disease progression in gastric cancer.

BACKGROUND: Little has been known about the role of non-coding RNA regulatory network in the patterns of growth and invasiveness of gastric cancer (GC) development. METHODS: MicroRNAs (miRNAs) microarray was used to screen differential miRNA expression profiles in Ming's classification. The significant differential expressions of representative miRNAs and their interacting circular RNA (circRNA) were confirmed in GC cell line and 63 pairs of GC samples. Then, a circRNA/miRNA network was constructed by bioinformatics approaches to identify molecular pathways. Finally, we explored the clinical value of the common targets in the pathway by using receiver operating characteristic curve and survival analysis. RESULTS: Significantly differential expressed miRNAs were found in two pathological types of GC. Both of miR-124 and miR-29b were consistently down-regulated in GC. CircHIPK3 could play a negative regulatory role on miR-124/miR-29b expression and associated with T stage and Ming's classification in GC. The bioinformatics analyses showed that targets expression of circHIPK3-miR-124/miR-29b axes in cancer-related pathways was able to predict the status of GC and associated with individual survival time. CONCLUSIONS: The targets of circHIPK3-miR-124/miR-29b axes involved in the progression of GC. CircHIPK3 could take part in the proliferation process of GC cell and may be potential biomarker in histological classification of GC.

Establishment and characterization of an expanding-type gastric cancer cell line by Ming's classification.

According to Ming's classification, gastric cancer (GC) can be divided into two types: expanding and infiltrative. The two types are readily recognizable by histology: expanding carcinomas grow en masse and by expansion, resulting in the formation of discrete tumour nodules, whereas in infiltrative carcinoma, tumour cells invade individually. Both types show varying degrees of cell maturation. The two types of carcinomas have vastly different pathological and clinical features. However, little is known concerning the mechanisms underlying these differences since no GC cell line models are available. For comprehensive and insightful analyses of mechanisms and treatment methods, new cell lines derived from expanding- and infiltrative-type gastric tumours are urgently needed. In the present study, we established an expanding-type GC cell line from a 72-year-old male patient. Different in vitro and in vivo methods were used to characterize the phenotypes of this cell line. This GC cell line was named XGC-2 and had an ~60 h doubling time. The cell line displayed strong colony formation and tumourigenicity in nude mice and had complicated chromosomal abnormalities. XGC-2 cells showed some markers of epithelial-to-mesenchymal transition (EMT), with decreased E-cadherin expression levels and increased vimentin expression levels. The XGC-2 cell line may be useful for future studies of GC development, progression, metastasis and therapy.