BackgroundGlucosamine 6-phosphate N-acetyltransferase (GNPNAT1) is a key enzyme in the hexosamine biosynthetic pathway (HBP), which functions as promoting proliferation in some tumors, yet its potential biological function and mechanism in lung adenocarcinoma (LUAD) have not been explored.MethodsThe mRNA differential expression of GNPNAT1 in LUAD and normal tissues was analyzed using the Cancer Genome Atlas (TCGA) database and validated by real-time PCR. The clinical value of GNPNAT1 in LUAD was investigated based on the data from the TCGA database. Then, immunohistochemistry (IHC) of GNPNAT1 was applied to verify the expression and clinical significance in LUAD from the protein level. The relationship between GNPNAT1 and epigenetics was explored using the cBioPortal database, and the miRNAs regulating GNPNAT1 were found using the miRNA database. The association between GNPNAT1 expression and tumor-infiltrating immune cells in LUAD was observed through the Tumor IMmune Estimation Resource (TIMER). Finally, Gene set enrichment analysis (GSEA) was used to explore the biological signaling pathways involved in GNPNAT1 in LUAD.ResultsGNPNAT1 was upregulated in LUAD compared with normal tissues, which was verified through qRT-PCR in different cell lines (P < 0.05), and associated with patients’ clinical stage, tumor size, and lymphatic metastasis status (all P < 0.01). Kaplan–Meier (KM) analysis suggested that patients with upregulated GNPNAT1 had a relatively poor prognosis (P < 0.0001). Furthermore, multivariate Cox regression analysis indicated that GNPNAT1 was an independent prognostic factor for LUAD (OS, TCGA dataset: HR = 1.028, 95% CI: 1.013–1.044, P < 0.001; OS, validation set: HR = 1.313, 95% CI: 1.130–1.526, P < 0.001). GNPNAT1 overexpression was correlated with DNA copy amplification (P < 0.0001), low DNA methylation (R = −0.52, P < 0.0001), and downregulation of hsa-miR-30d-3p (R = −0.17, P < 0.001). GNPNAT1 expression was linked to B cells (R = −0.304, P < 0.0001), CD4+T cells (R = −0.218, P < 0.0001), and dendritic cells (R = −0.137, P = 0.002). Eventually, GSEA showed that the signaling pathways of the cell cycle, ubiquitin-mediated proteolysis, mismatch repair and p53 were enriched in the GNPNAT1 overexpression group.ConclusionGNPNAT1 may be a potential prognostic biomarker and novel target for intervention in LUAD.
Background: The clinical benefit of immunotherapy has been limited to a small subset of patients with cancer. Several clinical trials with immune checkpoint inhibitors in multiple cancers have shown some improvement in obese patients. However, how obesity regulates the immune microenvironment remains unclear. Methods: Bioinformatic analysis was used to discover immune microenvironmental-related genes associated with body mass index (BMI). The expression of ICOS in tumor tissues was detected using western blot, immunohistochemistry, quantitative real-time polymerase chain reaction (RT-qPCR) and flow cytometry. RT-qPCR was used to measure the expression of miR-27a-3p. The interaction between miR-27a-3p and ICOS was confirmed by dual-luciferase reporter assay. Functional testing of T cells based on proliferation and interferon (IFN)-gamma secretion was performed using ELISA and flow cytometry. Results: ICOS, an immune microenvironment-related gene, was significantly upregulated in obese patients with lung adenocarcinoma (LUAD). MiR-27a-3p showed a negative correlation with ICOS and suppressed the expression of ICOS. We determined that dipocyte-derived exo-miR-27a-3p could alter the tumor microenvironment by inhibiting ICOS + T cell proliferation and IFN-gamma secretion in vitro. Conclusions: Adipocyte-derived exo-miR-27a-3p can inhibit ICOS + T cell proliferation and IFN-gamma secretion. The upregulation of ICOS + T cell functions caused by the downregulation of miR-27a-3p in adipose tissue derived exosomes is one of the potential mechanisms for the improved efficacy of immunotherapy in obese LUAD patients.
Background Anticancer treatment-related heart events is a major concern. However, the frequent occurrence time of cardiac death and the association between cardiac-specific mortality (CSM) and various lung lobes among non-elderly non-small cell lung cancer (NSCLC) patients after chemotherapy or radiotherapy (RT) are uncertain. Methods Data of patients aged 20–59 years and diagnosed with NSCLC during 1975–2014 were extracted from the Surveillance, Epidemiology and End Results (SEER) database. We divided them into four groups: no chemotherapy or RT, chemotherapy-only, RT-only and chemoradiation therapy (CRT). The Fine and Gray model was applied to evaluate the risks; the cumulative curves of CSM were established by Gray’s test. Furthermore, the forest graphs delineated the hazards of different tumor subsites to CSM as the survival time prolonged. Eventually, we analyzed and elucidated the tendency of CSM decade by decade. Results We identified 121,302 patients and 3,423 died of heart diseases. In chemotherapy-only group, age, sex, race, marital status and surgery were significantly correlated to CSM while the subsite location of tumor was the key risk among RT-only patients. The hazard ratio (HR) of CSM was greatest in 2–5 years after RT (P=0.008, HR =2.30). CSMs of chemotherapy (P=0.130, HR =2.480) and CRT (P=0.028, HR =2.600) peaked in 1985–1994 and decreased sharply hereafter, whereas the CSMs of RT-only declined over time. Conclusions The risks of CSM after chemotherapy were similar to the common hazards of heart diseases; tumor in the left-lower lobe was a remarkable risk for patients receiving RT-only and the frequent occurrence of cardiac death was from the second year after RT. The CSMs of chemotherapy and CRT culminated in 1985–1994 and then descended; it declined all the time in RT-only group.
BackgroundMitochondria are the core organelle of cellular energy and metabolism, also closely related to the growth and survival of cancer cells. This research aimed to discover and evaluate a promising prognostic biomarker, a novel mitochondrial gene—Sideroflexin1 (SFXN1), for lung adenocarcinoma (LUAD).ResultsAnalysis of 594 samples from The Cancer Genome Atlas (TCGA) Lung Cancer Cohort, this present study indicated that SFXN1/2/4/5 were overexpressed in LUAD tissue compared with normal lung tissue whereas only the SFXN1 was associated significantly with the overall survival (OS) from the Kaplan-Meier survival analysis (p=0.00093), suggesting that SFXN1 could be a potential prognostic biomarker. Furthermore, the logistic regression of the correlation of clinicopathological features and the expression status of SFXN1 from 522 patients with LUAD in TCGA revealed that the expression level of SFXN1 was related to Eastern Cooperative Oncology Group (ECOG), clinical stage, tumor size and lymph nodes invasion (all p<0.05). Additionally, overexpression of SFXN1 remained associated positively and independently with a worse prognosis after the multivariate Cox regression (HR=1.486, p=0.022). Functionally, SFXN1 involved in the cell cycle, specifically in DNA replication and meiosis, ATPase activity and folate-dependent one-carbon metabolism from the outcomes of Eastern Cooperative Oncology Group (KEGG) and Gene Ontology (GO) enrichment. ConclusionSFXN1 might promote the proliferation and metabolism of cancer cells and function as a prognostic indicator for LUAD, which may contribute to the development of targeted therapy and the emergence of metabolism-based treatment in clinical practice.
Recently, the antibacterial peptides (bacteriocin) have spurred interest of scholars, and many studies on Lactic acid bacteria (LAB) and bacteriocin have been carried out. With the improvement of living standard and health awareness, people tend to pay more attention to food safety. Chemical preservatives are rejected because of their residual properties and toxicity. Applying antibacterial peptides, which serve as natural preservation, to food industry is an inevitable trend[1]. In this paper, the classification of LAB antimicrobial peptides and their application in food system are reviewed. The classification of bacteriocin, the current major food packaging technology, the application of LAB bacteriocin in different industries have been discussed.
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