ABSTRACT
Effective diagnosis and understanding of the mechanism of intrapulmonary metastasis (IM) from multiple primary lung cancers (MPLC) aid clinical management. However, the actual detection panels used in the clinic are variable. Current research on tumor microenvironment (TME) of MPLC and IM is insufficient. Therefore, additional investigation into the differential diagnosis and discrepancies in TME between two conditions is crucial. Two hundred and fourteen non-small cell lung cancer patients with multiple tumors were enrolled and 507 samples were subjected to DNA sequencing (NGS 10). Then, DNA and RNA sequencing (master panel) were performed on the specimens from 32 patients, the TME profiles between tumors within each patient and across patients and the differentially expressed genes were compared. Four patients were regrouped with NGS 10 results. Master panel resolved the classifications of six undetermined patients. The TME in MPLC exhibited a high degree of infiltration by natural killer (NK) cells, CD56dim NK cells, endothelial cells, etc., Pâ <â 0.05. Conversely, B cells, activated B cells, regulatory cells, immature dendritic cells, etc., Pâ <â 0.001, were heavily infiltrated in the IM. NECTIN4 and LILRB4 mRNA were downregulated in the MPLC (Pâ <â 0.0001). Additionally, NECTIN4 (Pâ <â 0.05) and LILRB4 were linked to improved disease-free survival in the MPLC. In conclusion, IM is screened from MPLC by pathology joint NGS 10 detections, followed by a large NGS panel for indistinguishable patients. A superior prognosis of MPLC may be associated with an immune-activating TME and the downregulation of NECTIN4 and LILRB4 considered as potential drug therapeutic targets.
Subject(s)
Carcinoma, Non-Small-Cell Lung , High-Throughput Nucleotide Sequencing , Lung Neoplasms , Transcriptome , Tumor Microenvironment , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , High-Throughput Nucleotide Sequencing/methods , Male , Female , Tumor Microenvironment/genetics , Middle Aged , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Aged , Neoplasms, Multiple Primary/genetics , Neoplasms, Multiple Primary/pathology , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/genetics , Prognosis , Genomics/methods , Gene Expression Profiling , Nectins/genetics , Killer Cells, Natural/immunologyABSTRACT
OBJECTIVE: Based on the theory that long non-coding RNAs (lncRNAs) sponge microRNAs (miRNAs) to engage in cervical cancer development, this work was set out to investigate the possible role of lncRNA taurine upregulated gene 1 (TUG1) and miR-381-3p in the development of cervical cancer. METHODS: TUG1, miR-381-3p and murine double minute 2 (MDM2) expression were measured in cervical cancer tissues and cells. The nexus between TUG1 and clinicopathological features of cervical cancer was discussed. The biological functions of TUG1, miR-381-3p and MDM2 on cervical cancer cell process were interpreted via gain- and loss-of-function experiments. Also, tumor xenograft in nude mice was conducted in vivo. The interactions between TUG1, miR-381-3p and MDM2 were identified. RESULTS: TUG1 and MDM2 raised while miR-381-3p reduced in cervical cancer. TUG1 expression was related to tumor size, differentiation, international federation of gynecology and obstetrics stage and lymph node metastasis of cervical cancer. Restored miR-381-3p, depleted TUG1 or reduced MDM2 decreased viability, colony-forming, migration and invasion abilities, and facilitated apoptosis of cervical cancer cells. Xenografted tumors grew slowly upon injection with restored miR-381-3p and depleted TUG1. TUG1 bound to miR-381-3p and miR-381-3p targeted MDM2. CONCLUSION: On all accounts, this present study provides evidence that silencing TUG1 depressed cervical cancer cell progression through miR-381-3p/MDM2 axis, highlighting a theoretical basis for cervical cancer treatment.
Subject(s)
MicroRNAs/metabolism , Proto-Oncogene Proteins c-mdm2/biosynthesis , RNA, Long Noncoding/metabolism , Uterine Cervical Neoplasms/metabolism , Adult , Aged , Animals , Apoptosis/physiology , Cell Differentiation/physiology , Cell Line, Tumor , Cell Proliferation/physiology , Cell Survival/genetics , Female , Humans , Mice , Mice, Nude , MicroRNAs/genetics , Middle Aged , Proto-Oncogene Proteins c-mdm2/genetics , Proto-Oncogene Proteins c-mdm2/metabolism , RNA, Long Noncoding/genetics , Transcriptional Activation , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Xenograft Model Antitumor AssaysABSTRACT
Expression of bromodomain protein 4 (BRD4) has been reported to predict a worse prognosis in solid tumors. However, its expression profile and prognostic value in gastric carcinoma (GC) remains unknown. Here we investigated BRD4 expression in GC and explored its association with patient survival. Tissue samples were obtained from 95 GC patients who underwent surgical resection to remove the primary tumor from January 2009 to December 2010. Immunohistochemistry was used to detect the expression of BRD4 in GC tissues and adjacent normal tissues. Kaplan-Meier survival curves and Cox proportional hazards regression were used to analyze the data of BRD4 expression profile and clinicopathological characteristics. Immunohistochemical analysis revealed BRD4 was overexpressed in GC tissue compared with adjacent normal tissue. BRD4 expression was significantly associated with TNM stage (p < 0.001), lymphatic permeation (p = 0.011), and vital status at the end of follow-up (p < 0.001). Kaplan-Meier survival curves and the log-rank test demonstrated that higher BRD4 expression was an adverse predictive factor for survival in GC. Multivariate analysis by Cox proportional hazards regression revealed that BRD4 expression was an independent worse prognostic factor in GC. In conclusion, BRD4 could act as a potential biomarker for prognostic assessment of GC.
Subject(s)
Biomarkers, Tumor , Nuclear Proteins/metabolism , Stomach Neoplasms/metabolism , Stomach Neoplasms/mortality , Transcription Factors/metabolism , Adult , Aged , Cell Cycle Proteins , Female , Gene Expression , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Grading , Neoplasm Metastasis , Neoplasm Staging , Nuclear Proteins/genetics , Prognosis , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Transcription Factors/geneticsABSTRACT
Three series of butenolide-containing dithiocarbamates were designed and synthesized. Their anti-tumor activity in vitro was evaluated. Among them compound I-14 exhibited broad spectrum anti-cancer activity against five human cancer cell lines with IC(50) <30 µM. Structure-activity relationship analysis showed that the introduction of dithiocarbamate side chains on the C-3 position of butenolide was crucial for anti-tumor activity.
