BackgroundGlucose-6-phosphate isomerase (GPI) plays an important role in glycolysis and gluconeogenesis. However, the role of GPI in lung adenocarcinoma (LUAD) remains unclear.MethodsAll original data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and integrated via R 3.2.2. GPI expression was explored with TCGA, GEO, and Oncomine databases. Immunohistochemistry staining was used to analyze GPI expression in clinical specimens. The correlations between GPI and cancer immune characteristics were analyzed via the TIMER and TISIDB databases. GPI-specific siRNAs were used to verify the role of GPI expression on cell proliferation and cell cycle distribution.ResultsIn general, GPI is predominantly overexpressed and has reference value in the diagnosis and prognostic estimation of LUAD. Upregulated GPI was associated with poorer overall survival, clinical stage, N stage, and primary therapy outcome in LUAD. Mechanistically, we identified a hub gene that included a total of 56 GPI-related genes, which were tightly associated with the cell cycle pathway in LUAD patients. Knockdown of GPI induced cell proliferation inhibition and cell cycle arrest. GPI expression was positively correlated with infiltrating levels of Th2 cells and regulatory T cells (Tregs); in contrast, GPI expression was negatively correlated with infiltrating levels of CD8+ T cells, central memory T cells, dendritic cells, macrophages, mast cells, and eosinophils. GPI was negatively correlated with the expression of immunostimulators, such as CD40L, IL6R, and TMEM173, in LUAD.ConclusionGPI may play an important role in the cell cycle and can be used as a prognostic biomarker for determining the prognosis and immune infiltration in LUAD.

Radiotherapy has been reported to cause cancer metastasis. Thus, a new strategy for radiotherapy must be developed to avoid this side effect. A549 cells were exposed to radiation to induce an epithelial-mesenchymal transition (EMT) cell model. Real-time PCR and western blotting were used to detect mRNA and protein expression levels, and Transwell invasion and wound healing assays were used to detect cell migration and invasion. ELISA was used to detect soluble E-cadherin (sE-cad) secretion. siRNA was used to silence MMP9 expression. The results show that A549R cells exhibited an EMT phenotype with increased E-cadherin, N-cadherin, Snail, Slug, vimentin and Twist expression and decreased pan-keratin expression. sE-cad levels were increased in A549R cells and in the serum of NSCLC patients with distant metastasis. Exogenous sE-cad treatment and sE-cad overexpression promoted A549R and A549 cell migration and invasion. In contrast, blocking sE-cad attenuated A549 cell migration and invasion. Curcumin inhibited sE-cad expression and reversed EMT induced by radiation. Furthermore, curcumin suppressed sE-cad-enhanced A549 and A549R cell migration and invasion. Curcumin inhibited MMP9 expression, and silencing MMP9 suppressed sE-cad expression. Taken together, we found a nonclassic EMT phenomenon induced by radiation. Curcumin inhibits NSCLC migration and invasion by suppressing radiation-induced EMT and sE-cad expression by decreasing MMP9 expression.

Background/AimsXRCC1 (X-ray repair cross-complementing protein 1) expression and its single nucleotide polymorphism XRCC1 rs25487 (G>A) may be related to radiotherapy-related cancer prognosis or radiation-induced side effects. However, this association is controversial. We performed a bioinformatic analysis and a meta-analysis to obtain comprehensive results.MethodsTCGA data sets and eligible publications published before November 31, 2020 were retrieved by searching the PubMed, Web of Science and CNKI (China National Knowledge Infrastructure) databases. ORs (odds ratios) and HRs (hazard ratios) with their corresponding 95% CIs (confidence intervals) were calculated to evaluate associations. For XRCC1 single nucleotide polymorphisms, we employed three types of comparisons: GA vs GG, AA vs GG and GA+AA vs GG.ResultsSixty nine articles with 10232 patients and 17 TCGA data sets with 2705 patients were included in the analysis. We observed that high XRCC1 expression was associated with an increased risk of minor treatment response and poor overall survival, XRCC1 rs25487 was associated with reduced risk of minor treatment response in esophageal cancer and an increased risk of high-grade side effects in head and neck cancer.ConclusionThe results suggest that XRCC1 expression and rs25487 polymorphism are prognostic factors for patients receiving radiotherapy-related treatment. Considering the insufficient treatment parameters provided and the various sample sizes in most of the studies, we suggest that genetic association studies related to radiation-based treatment should include more cancer types with sufficient statistical power and more detailed clinical parameters.