ABSTRACT
Lung cancer is the most commonly occurring cancer attributed to the leading cause of cancer-related deaths globally. Non-small cell lung cancer (NSCLC) comprises 85% to 90% of lung cancers. The survival rate of patients with advanced stage NSCLC is in months. Moreover, the underlying molecular mechanisms still remain to be understood.We used 2 sets of microarray data in combination with various bioinformatic approaches to identify the differentially expressed genes (DEGs) in NSCLC patients.We identified a total of 419 DEGs using the Limma package. Gene set enrichment analysis demonstrated that "Citrate cycle (TCA cycle)," "RNA degradation," and "Pyrimidine metabolism" pathways were significantly enriched in the NSCLC samples. Gene Ontology annotations of the 419 DEGs primarily comprised "glycosaminoglycan binding," "cargo receptor activity," and "organic acid binding." Kyoto Encyclopedia of Genes and Genomes analysis revealed that DEGs were enriched in pathways related to "Malaria," "Cell cycle," and "IL-17 signaling pathway." Protein protein interaction network analysis showed that the hub genes constituted of CDK1, CDC20, BUB1, BUB1B, TOP2A, CCNA2, KIF20A, CCNB1, KIF2C, and NUSAP1.Taken together, the identified hub genes and pathways will help understand NSCLC tumorigenesis and develop prognostic markers and therapeutic targets against NSCLC.
Subject(s)
Carcinogenesis/pathology , Carcinoma, Non-Small-Cell Lung/genetics , Differential Threshold , Carcinogenesis/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Humans , Microarray Analysis/methodsABSTRACT
OBJECTIVE: To investigate the roles of the γ-aminobutyric acid (GABA) in the metastasis of hepatocellular carcinoma (HCC) and to explore the potential of a novel therapeutic approach for the treatment of HCC. METHODS: The expression levels of GABA receptor subunit genes in various HCC cell lines and patients' tissues were detected by quantitative real-time polymerase chain reaction and Western blot analysis. Transwell cell migration and invasion assays were carried out for functional analysis. The effects of GABA on liver cancer cell cytoskeletal were determined by immunofluorescence staining. And the effects of GABA on HCC metastasis in nude mice were evaluated using an in vivo orthotopic model of liver cancer. RESULTS: The mRNA level of GABA receptor subunits varied between the primary hepatocellular carcinoma tissue and the adjacent non-tumor liver tissue. GABA inhibited human liver cancer cell migration and invasion via the ionotropic GABAA receptor as a result of the induction of liver cancer cell cytoskeletal reorganization. Pretreatment with GABA also significantly reduced intrahepatic liver metastasis and primary tumor formation in vivo. CONCLUSIONS: These findings introduce a potential and novel therapeutic approach for the treatment of cancer patients based on the modulation of the GABAergic system.
ABSTRACT
AIM: To analyze the influence factors and formation of extrahepatic collateral arteries (ECAs) in unresectable hepatocellular carcinoma (HCC) with or without chemoembolization. METHODS: Detailed histories of 35 patients with 39 ECAs of HCC and images including computerized tomography scan, digital subtraction angiography were reviewed carefully to identify ECAs of HCC, ECAs arising from, and anatomic location of tumors in liver. Tumor sizes were measured, and relations of ECAs with times of chemoembolization, tumor size, and the anatomic tumor location were analyzed. Complications were observed after chemoembolization through ECAs of HCC with different techniques. RESULTS: Influence factors of formation of ECAs of HCC included the times of repeated chemoembolization, the location of tumors in liver, the tumor size and the types of chemoembolization. ECAs in HCC appeared after 3-4 times of chemoembolization (17.9%), but a higher frequency of ECAs occurred after 5-6 times of chemoembolization (56.4%). ECAs presented easily in peripheral areas (71.8%) of liver abutting to the anterior, posterior abdominal walls, the top right of diaphragm and right kidney. ECAs also occurred easily after complete obstruction of the trunk arteries supplying HCCs or the branches of proper hepatic arteries. Extrahepatic collaterals of HCC originated from right internal thoracic (mammary) artery (RITA, 5.1%), right intercostal artery (RICA, 7.7%), left gastric artery (LGA, 12.8%), right inferior phrenic artery (RIPA, 38.5%), omental artery (OTA, 2.6%), superior mesenteric artery (SMA, 23.1%), and right adrenal and renal capsule artery (RARCA, 10.3%), respectively. The complications after chemoembolization attributed to no super selective catheterization. CONCLUSION: The formation of ECAs in unresectable HCC is obviously correlated with multiple chemoembolization, tumor size, types of chemoembolization, anatomic location of tumors. Extrahepatic collaterals in HCC are corresponding to the tumor locations in liver.
