Acquired crizotinib-resistant pulmonary adenocarcinoma and subsequent primary gallbladder cancer: A case report.

RATIONALE: Proto-oncogene-oriented targeted therapy has limited benefits in elderly patients with multiple primary tumors. PATIENT CONCERNS: A woman with anaplastic lymphoma kinase-positive lung adenocarcinoma developed acquired resistance after 3 years of targeted therapy with crizotinib. DIAGNOSES: Diagnosis of unexpected subsequent primary gallbladder tumor. INTERVENTIONS: Lenvatinib was administered therapeutically. Meanwhile, next-generation sequencing results before and after crizotinib treatment were analyzed by comparing the tumor-driving mutation genes with bioinformatics methods. OUTCOMES: The patient died of ascites and liver failure. Furthermore, bypass activation was found to be the main reason for acquired drug resistance for this patient, and the abnormal expression of tumor suppressor genes and senescence-related genes was the likely cause of the second primary tumor. LESSONS: A bioinformatic comparison of pre- and post-treatment sequencing in elderly oncology patients is of interest. CONCLUSIONS: For diagnosing, precision bioinformatics analysis and repeat biopsy are equally valuable. For therapy, potential therapy such as p53 gene replacement therapy and CAR-T therapy need to be practiced for senescence-related conditions.

Transcriptome-Wide m6A Methylome and m6A-Modified Gene Analysis in Asthma.

N6-methyladenosine (m6A) modification is one of the most prevalent RNA modification forms and is an important posttranscriptional mechanism for regulating genes. In previous research, we found that m6A regulator-mediated RNA methylation modification was involved in asthma; however, the specific modified genes are not clear. In this study, we systematically evaluated the transcriptome-wide m6A methylome and m6A-modified genes in asthma. Here, we performed two high-throughput sequencing methods, methylated RNA immunoprecipitation sequencing (MeRIP-seq), and RNA sequencing (RNA-seq) to identify key genes with m6A modification in asthma. Through difference analysis, we found that 416 methylation peaks were significantly upregulated and 152 methylation peaks were significantly downregulated, and it was mainly distributed in 3' UTR. Furthermore, compared with the control group, there were 2,505 significantly upregulated genes and 4,715 significantly downregulated genes in the asthma group. Next, through a combined analysis of transcriptome and differential peaks, 14 differentially expressed genes related to RNA methylation modification were screened. Finally, through 87 health controls and 411 asthma cases from the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) program, we verified three m6A-modified key genes (BCL11A, MATK, and CD300A) and found that they were mainly distributed in exons and enriched in 3' UTR. Our findings suggested that intervening in m6A-modified genes may provide a new idea for the treatment of asthma.

Determining Pharmacological Mechanisms of Chinese Incompatible Herbs Fuzi and Banxia in Chronic Obstructive Pulmonary Disease: A Systems Pharmacology-Based Study.

Aconiti Lateralis Radix Praeparata (Fuzi) and Pinelliae Rhizoma (Banxia) are among the 18 incompatible medications that are forbidden from use in one formulation. However, there is increasing evidence implying that this prohibition is not entirely correct. According to the theory of Chinese traditional medicine, they can be used for the treatment of chronic obstructive pulmonary disease (COPD). Thus, we analyzed the possible approaches for the treatment of COPD using network pharmacology. The active compounds of Fuzi and Banxia (FB) were collected, and their targets were identified. COPD-related targets were obtained by analyzing the differentially expressed genes between COPD patients and healthy individuals, which were expressed using a Venn diagram of COPD and FB. Protein-protein interaction data and network regarding COPD and drugs used were obtained. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted. The gene-pathway network was constructed to screen the key target genes. In total, 34 active compounds and 47 targets of FB were identified; moreover, 7,153 differentially expressed genes were identified between COPD patients and healthy individuals. The functional annotations of target genes were found to be related to mechanisms such as transcription, cytosol, and protein binding; furthermore, 68 pathways including neuroactive ligand-receptor interaction, Kaposi sarcoma-associated herpesvirus infection, apoptosis, and measles were significantly enriched. FOS CASP3, VEGFA, ESR1, and PTGS2 were the core genes in the gene-pathway network of FB for the treatment of COPD. Our results indicated that the effect of FB against COPD may involve the regulation of immunological function through several specific biological processes and their corresponding pathways. This study demonstrates the application of network pharmacology in evaluating mechanisms of action and molecular targets of herb-opponents FB.