Gankyrin promotes the proliferation of gastric cancer and is associated with chemosensitivity.

Although gankyrin is involved in the tumorigenicity and metastasis of some malignancies, the role of gankyrin in gastric cancer is not clear. In this study, we evaluated the function and mechanism of gankyrin in gastric cancer. The effects of gankyrin on gastric cancer growth, proliferation, and chemosensitivity were determined. Gankyrin expression was significantly increased in gastric cancer compared to non-cancerous tissues. This expression significantly enhanced cancer cell proliferation and growth in vitro and in vivo. Suppression of gankyrin downregulated cyclin D1, cyclin E, proliferating cell nuclear antigen, phosphoinositide 3-kinase, AKT, p-PI3K, and p-AKT but upregulated Rb, p53, and p27. However, gankyrin overexpression led to opposite results. Downregulation of gankyrin expression enhanced chemosensitivity to 5-fluorouracil and cisplatin by inducing cell apoptosis. However, upregulation of gankyrin expression led to the opposite outcomes. Gankyrin enhanced gastric cancer cell proliferation by regulating cell cycle-related proteins and by activating PI3K/AKT signaling pathway. Gankyrin played an important role in gastric carcinogenesis and could be a potential effective therapeutic target for enhancing chemosensitivity to 5-fluorouracil and cisplatin.

Bone marrow mesenchymal stem cell transplantation improves radiation-induced heart injury through DNA damage repair in rat model.

Radiotherapy is an effective form of therapy for most thoracic malignant tumors. However, myocardial injury resulting from the high doses of radiation is a severe complication. Here we aimed to study the possibility of reducing radiation-induced myocardial injury with mesenchymal stem cell (MSC) transplantation. We used MSCs extracted from bone marrow (BMSCs) to transplant via the tail vein into a radiation-induced heart injury (RIHI) rat model. The rats were divided into six groups: a Sham group, an IRR (irradiation) group, and four IRR + BMSCs transplantation groups obtained at different time points. After irradiation, BMSC transplantation significantly enhanced the cardiac function in rats. By analyzing the expression of PPAR-α, PPAR-γ, TGF-ß, IL-6, and IL-8, we found that BMSC transplantation alleviated radiation-induced myocardial fibrosis and decreased the inflammatory reaction. Furthermore, we found that expression of γ-H2AX, XRCC4, DNA ligase4, and TP53BP1, which are associated with DNA repair, was up-regulated, along with increased secretion of growth factors SDF-1, CXCR4, VEGF, and IGF in rat myocardium in the IRR + BMSCs transplantation groups compared with the IRR group. Thus, BMSC transplantation has the potential to improve RIHI via DNA repair and be a new therapeutic approach for patients with myocardial injury.

Sodium glycididazole enhances the radiosensitivity of laryngeal cancer cells through downregulation of ATM signaling pathway.

The purpose of this study was to evaluate the radiation-enhancing effect of sodium glycididazole, and the corresponding mechanisms of action on laryngeal cancer cells. Two laryngeal cancer cell lines (Hep-2 and UT-SCC-19A) were irradiated with X-rays in the presence or absence of sodium glycididazole. Cell survival, DNA damage and repair, cell apoptosis, cell cycle distribution, expression of proteins related to cell cycle checkpoint, and apoptosis were measured. Significantly increased DNA damages, decreased cells in the G1 phase, arrested cells at G2/M phase, decreased DNA repair protein XRCC1 foci formation, and enhanced cell apoptosis were observed in laryngeal cell lines treated by sodium glycididazole combined with irradiation compared with the irradiation alone. The combined treatment downregulated the protein expressions of ataxia-telangiectasia mutated (ATM), p-ATM, CHK2, and P53 but upregulated the protein expressions of MDM2 and Cdk2. This study indicates that sodium glycididazole enhances the radiosensitivity of laryngeal cancer cells through downregulation of ATM signaling pathway in vitro and in vivo.

Proton therapy posterior beam approach with pencil beam scanning for esophageal cancer : Clinical outcome, dosimetry, and feasibility.

PURPOSE: The aim of this study is to present the dosimetry, feasibility, and preliminary clinical results of a novel pencil beam scanning (PBS) posterior beam technique of proton treatment for esophageal cancer in the setting of trimodality therapy. METHODS: From February 2014 to June 2015, 13 patients with locally advanced esophageal cancer (T3-4N0-2M0; 11 adenocarcinoma, 2 squamous cell carcinoma) were treated with trimodality therapy (neoadjuvant chemoradiation followed by esophagectomy). Eight patients were treated with uniform scanning (US) and 5 patients were treated with a single posterior-anterior (PA) beam PBS technique with volumetric rescanning for motion mitigation. Comparison planning with PBS was performed using three plans: AP/PA beam arrangement; PA plus left posterior oblique (LPO) beams, and a single PA beam. Patient outcomes, including pathologic response and toxicity, were evaluated. RESULTS: All 13 patients completed chemoradiation to 50.4 Gy (relative biological effectiveness, RBE) and 12 patients underwent surgery. All 12 surgical patients had an R0 resection and pathologic complete response was seen in 25 %. Compared with AP/PA plans, PA plans have a lower mean heart (14.10 vs. 24.49 Gy, P < 0.01), mean stomach (22.95 vs. 31.33 Gy, P = 0.038), and mean liver dose (3.79 vs. 5.75 Gy, P = 0.004). Compared to the PA/LPO plan, the PA plan reduced the lung dose: mean lung dose (4.96 vs. 7.15 Gy, P = 0.020) and percentage volume of lung receiving 20 Gy (V20; 10 vs. 17 %, P < 0.01). CONCLUSION: Proton therapy with a single PA beam PBS technique for preoperative treatment of esophageal cancer appears safe and feasible.

Pre-treatment neutrophil-to-lymphocyte ratio predicts prognosis in patients with locoregionally advanced laryngeal carcinoma treated with chemoradiotherapy.

OBJECTIVE: The aim of this study was to investigate the effect of neutrophil-to-lymphocyte ratio on the prognosis of patients with locoregionally advanced laryngeal carcinoma treated with chemoradiotherapy. METHODS: One hundred and twenty-five patients with locoregionally advanced laryngeal carcinoma (cT3-4 N0-3M0) treated with chemoradiotherapy were reviewed retrospectively. Chemoradiotherapy comprised external beam radiotherapy to the larynx (70 Gy) with three cycles of cisplatin at 3 week intervals. The survival rate was calculated using the Kaplan-Meier method, and a multivariate analysis was used to identify significant factors associated with prognosis, using a Cox proportional hazards model. RESULTS: During the median (range) follow-up of 45 months, the median neutrophil-to-lymphocyte ratio was 3.02. The high neutrophil-to-lymphocyte ratio group (neutrophil-to-lymphocyte ratio > 3.0) contained 69 patients and the low neutrophil-to-lymphocyte ratio group (neutrophil-to-lymphocyte ratio < 3.0) contained 46 patients. The low neutrophil-to-lymphocyte ratio group patients had a significantly higher chemoradiotherapeutic disease control rate (86.96 vs. 69.57%, P = 0.031). Forty-six patients had a low neutrophil-to-lymphocyte ratio (<3.0) before chemoradiotherapy and their progression-free survival and 75% overall survival were significantly better than that of the high neutrophil-to-lymphocyte ratio patients (P = 0.015, P = 0.045). Multivariate analysis showed that neutrophil-to-lymphocyte ratio and N stage were independent prognostic indicators for progression-free survival (with a hazard ratio of 1.79, P = 0.003 and a hazard ratio of 1.28, P = 0.034) and overall survival (with a hazard ratio of 1.51, P = 0.029 and a hazard ratio of 1.21, P = 0.043), respectively. CONCLUSION: Pre-treatment neutrophil-to-lymphocyte ratio is a useful prognostic marker in patients with locoregionally advanced laryngeal carcinoma treated with chemoradiotherapy.

Sestrin2 protects the myocardium against radiation-induced damage.

The purpose of this study was to investigate the role of Sestrin2 in response to radiation-induced injury to the heart and on the cardiomyopathy development in the mouse. Mice with genetic deletion of the Sestrin2 (Sestrin2 knockout mice [Sestrin2 KO]) and treatment with irradiation (22 or 15 Gy) were used as independent approaches to determine the role of Sestrin2. Echocardiography (before and after isoproterenol challenge) and left ventricular (LV) catheterization were performed to evaluate changes in LV dimensions and function. Masson's trichrome was used to assess myocardial fibrosis. Immunohistochemistry and Western blot were used to detect the capillary density. After 22 or 15 Gy irradiation, the LV ejection fraction (EF) was impaired in wt mice at 1 week and 4 months after irradiation when compared with sham irradiation. Compared to wt mice, Sestrin2 KO mice had significant reduction in reduced LVEF at 1 week and 4 months after irradiation. A significant increase in LV end-diastolic pressure and myocardial fibrosis and a significant decrease in capillary density were observed in irradiation-wt mice, as well as in irradiation-Sestrin2 KO mice. Sestrin2 involved in the regulation of cardiomyopathy (such as myocardial fibrosis) after irradiation. Overexpression of Sestrin2 might be useful in limiting radiation-induced myocardial injury.

Diagnosis of pancreatic cancer using ¹8F-FDG PET/CT and CA19-9 with SUVmax association to clinical characteristics.

PURPOSE: To assess the ability of 18F-FDG PET/CT alone or combined with CA19-9 to diagnose pancreatic cancer and to analyze the correlation between maximal standardized uptake value (SUVmax) and clinical characteristics. METHODS: Ninety-one patients diagnosed with pancreatic cancer using 18F-FDG PET/CT before treatment were analyzed. Definite diagnosis was by histology or cytology. The SUVmax of the primary tumor was used for the statistical analysis and, using the best cutoff value, the patients were divided into 2 groups: a high SUVmax group (SUV- max-5.49) and a low SUVmax group (SUVmax≤5.49). Logistic regression analysis and receiver operating characteristic (ROC) analysis were applied to analyze the effects of SUVmax and/or CA19-9 on the diagnosis of pancreatic cancer. RESULTS: Of 91 patients, 80 had pancreatic cancer and 11 had benign conditions. The ROC curve analysis of the SUVmax yielded a best cutoff value of 5.49. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ¹8F-FDG PET/CT alone in the diagnosis of pancreatic cancer were 67.5, 72.73, 94.74, 23.53, and 68.13%, respectively, while these indices for ¹8F-FDG PET/CT combined with CA19-9 increased to 96.25, 63.64, 95.06, 70, and 92.31%, respectively. The area under the curve (AUC) of the SUVmax combined with CA19-9 was 0.94, which was significantly higher than that of the SUVmax or CA19-9 alone (p<0.05). The SUVmax value and CA19-9 levels in pancreatic cancer patients were significantly higher than those with benign conditions (p<0.05). Only the SUVmax in the pancreatic cancer patient group was associated with tumor size (p<0.05). CONCLUSIONS: 18F-FDG PET/CT is a common examination for diagnosing pancreatic cancer, and the SUVmax combined with the CA19-9 level can significantly improve the sensitivity and accuracy in the diagnosis of pancreatic cancer. SUVmax is merely indicative of the volume of pancreatic cancer.

Radiation enhancing effects of sanazole and gemcitabine in hypoxic breast and cervical cancer cells in vitro.

AIM OF THE STUDY: Sanazole and gemcitabine have been proven clinically as hypoxic cell radiosensitisers. This study was conducted to determine the radiation enhancing effects of sanazole and gemcitabine when administered together at relevant concentrations into hypoxic human MCF-7 and HeLa cells. MATERIAL AND METHODS: A 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay was used to evaluate the number of surviving cells. Cell cycle was determined by flow cytometry. Cell surviving fractions were determined by the standard in vitro colony formation assay. RESULTS: The cell colony formation assay indicated that the radiosensitivity of hypoxic MCF-7 and HeLa cells was enhanced by sanazole or gemcitabine. The combination of the two drugs displayed significant radiation enhancing effects at the irradiation doses of 6, 8, and 10 Gy in both cell lines, which were arrested in the S phase. CONCLUSIONS: This study indicated that the co-administration of the two drugs may result in a beneficial gain in radio-therapy for hypoxic breast cancer and cervical cancer.

Influence of cancer-directed surgery on the prognosis of liver metastases from gastric cancer.

There are controversial about the application of cancer-directed surgery (CDS) in patients with liver metastases from gastric cancer, with improved responses to chemotherapy and targeted treatments, the role of CDS in metastatic gastric cancer to the liver needs to be revisited. This study aimed to evaluate the effect of CDS on patients with liver metastases from gastric cancer. Data for patients with liver metastases from gastric cancer were extracted from the population-based Surveillance, Epidemiology, and End Results (SEER) database. A total of 958 individuals were enrolled, 285 in the CDS group and 673 in the non-cancer guided surgery (Non-CDS) group. Following propensity score matching (PSM) analysis at 1:1 in the two groups,285 were included in the survival analysis for each group. Kaplan-Meier values and Cox proportional risk models were used to estimate the effect of CDS on patients' prognoses. Compared with the Non-CDS group, the CDS group significantly prolonged the median overall survival from 4 months (95% confidence interval [CI] 3-5) to 11 months (95% CI 8-12), p value < 0.001. Overall survival (OS) at 1 year was higher in the CDS group than in the Non-CDS group, at 44% (95 CI 38-50) and 25% (95 CI 20-30), respectively. OS at 3 years was also higher in the CDS group than in the Non-CDS group, at 24% (95 CI 19-29) and 6% (95 CI 3-9), respectively. Multivariate analysis showed that Non-CDS (hazard ratio[HR] = 2.26, 95% CI 1.88-2.72, p value < 0.001) was an adverse independent prognostic factor for patients. This study concludes that CDS prolonged survival in patients with gastric cancer with liver metastases. Due to the lack of information on the quality of life, biomarkers, targeted therapies, and immunotherapy in the SEER database, the observed improved survival rates following CDS of hepatic metastasis from gastric cancer requires prospective studies that take these factors into account to properly address the survival advantages and impact on quality of life of such a method.

Circulation insulin-like growth factor peptides and colorectal cancer risk: an updated systematic review and meta-analysis.

Insulin-like growth factor peptides, play an important role in regulating cell growth, differentiation, and apoptosis, which has been demonstrated to promote the development of cancer. The purpose of our study is to assess the association between circulation insulin-like growth factor peptides and colorectal cancer (CRC) risk. We searched Medline, EMBASE, OVID and Web of Science and picked up epidemiological studies that satisfied our inclusion criteria. A meta-analysis of 19 epidemiological studies containing 5,155 cases and 9,420 controls related with the association of circulation insulin-like growth factor peptides and CRC risk was carried out. Meta-analysis showed that high level IGF-I and IGF-II significantly increased CRC risk, (OR = 1.25, 95% CI: 1.08-1.45 for IGF-I; OR = 1.52, 95% CI: 1.16-2.01 for IGF-II; OR = 0.85, 95% CI: 0.70-1.03 for IGFBP-1; OR = 0.77, 95% CI: 0.41-1.43 for IGFBP-2 and OR = 0.88, 95% CI: 0.71-1.10 for IGFBP-3). Subgroup analysis showed that the increased cancer risk by IGF-I was more distinguished in colon cancer (OR = 1.35, 95% CI: 1.04-1.75) and Caucasian (OR = 1.32, 95% CI: 1.12-1.56). Our meta-analysis provides comprehensive support for a role of circulation IGF-I and IGF-II in the etiology of CRC.

Radiation enhancing effects with the combination of sanazole and irinotecan in hypoxic HeLa human cervical cancer cell line.

PURPOSE: This study was conducted to determine the synergistic radiation sensitizing effects of the combination of sanazole and irinotecan in hypoxic cervical cancer HeLa human tumor cell line. METHODS: The 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay was used to evaluate the number of surviving cells. Cell cycle was determined by flow cytometry. Surviving cell fractions were determined by the standard in vitro colony formation assay. RESULTS: The MTT assay showed that the presence of irinotecan with or without sanazole reduced significantly the cells' viability. Flow cytometry demonstrated that the combination of sanazole and irinotecan led to more HeLa cells blocked in G(2) phase. Cell colony formation assay indicated that the radiosensitivity of hypoxic HeLa cells was enhanced by sanazole and/or irinotecan. CONCLUSION: This study showed that the radiation enhancing effects produced by the combination sanazole and irinotecan was significant in hypoxic HeLa cells, which were arrested in the G(2) phase of the cell cycle. This study may provide a new combination modality of radiosensitizers in the radiotherapy of cervical cancer.

C-reactive protein level predicts prognosis in patients with locoregionally advanced laryngeal carcinoma treated with chemoradiotherapy.

The aim of this study was to investigate the effect of C-reactive protein (CRP) level on the prognosis of patients with locoregionally advanced laryngeal carcinoma treated with chemoradiotherapy. Fifty-seven patients with locoregionally advanced laryngeal carcinoma (cT3-4, N0-3, M0) treated with chemoradiotherapy were reviewed retrospectively. Chemoradiotherapy comprised external beam radiotherapy to the larynx (70 Gy) with three cycles of cisplatin at 3-week intervals. Elevated CRP was defined as >8 mg/L. The survival rate was calculated using the Kaplan-Meier method, and a multivariate analysis was used to identify significant factors associated with prognosis, using a Cox proportional hazards model. During the median (range) follow-up of 5 years (1.3-5), 29 patients died from laryngeal cancer; the 5-year cancer-specific survival (CSS) rate was 49.12%. Fifteen patients had a high CRP level before chemoradiotherapy (>8 mg/L), and their CSS rate was significantly worse than that in the remaining patients (P = 0.003). Multivariate analysis showed that CRP and tumor site were independent prognostic indicators for CSS, with a hazard ratio of 2.66 (95% confidence interval (CI), 1.22-5.82; P = 0.014) and a hazard ratio of 1.67 (95% CI, 1.01-2.77; P = 0.045), respectively. Of those with elevated CRP, the CRP levels of ten patients became normal after chemoradiotherapy, of whom four were alive with no evidence of recurrence or metastasis during the follow-up. By contrast, all six with no CRP normalization after chemoradiotherapy died within 3.8 years. The elevation of CRP before treatment predicts a poor prognosis in patients with locoregionally advanced laryngeal carcinoma treated with chemoradiotherapy.

Up-regulation of peroxisome proliferator-activated receptor gamma in radiation-induced heart injury in rats.

To explore the expression level and the role of peroxisome proliferator-activated receptor gamma (PPAR-γ) in radiation-induced heart injury in a rat model, thirty-two Sprague-Dawley rats were divided into three groups (the control group, the 15-Gy irradiation group and the 18-Gy irradiation group). Experimental animals were exposed to radiation generated by a linear accelerator at the chest and killed after 3 months. Heart tissues from these animals were removed for Masson staining, PPAR-γ immunohistochemical staining, Western blot analysis and real-time polymerase chain reaction assay (RT-PCR). In addition, the protein expression of matrix metalloprotein-1 (MMP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and transforming growth factor type beta1 (TGF-ß1), all of which are associated with fibrosis, was measured. Masson staining revealed significant myocardial fibrosis, degeneration and necrosis in rats exposed to radiation. The results of immunohistochemical staining and Western blot analysis showed that PPAR-γ protein expression in hearts of the irradiation groups was significantly higher than in the control group, especially in myocardium and vascular endothelial (p < 0.05). RT-PCR results also showed a parallel increase in PPAR-γ mRNA expression in the heart of the irradiation groups compared with the control group (p < 0.05). The expression of MMP-1 protein was not significantly different in three groups (p > 0.05). The expression of TIMP-1 and TGF-ß1 proteins was, however, higher in two irradiation groups than in the control group (p < 0.05). These data demonstrate that PPAR-γ expression is up-regulated on both mRNA and protein levels in heart injured by radiation. PPAR-γ may play an important role in radiation-induced heart injury.

Chemotherapy- and Immune-Related Gene Panel in Prognosis Prediction and Immune Microenvironment of SCLC.

Small-cell lung cancer (SCLC) is a highly proliferative, invasive lung cancer with poor prognosis. Chemotherapy is still the standard first-line treatment for SCLC, but many patients relapse due to chemoresistance. Along with advances in immunology, it is essential to investigate potential indicators of the immune response and the prognosis of SCLC. Using bioinformatics analysis, we identified 313 differentially expressed genes (DEGs) in SCLC and normal lung samples, and we found that four upregulated genes (TOP2A, CDKN2A, BIRC5, and MSH2) were associated with platinum resistance, while immune-related genes (HLA family genes) were downregulated in SCLC. Then, a prognostic prediction model was constructed for SCLC based on those genes. Immune cell infiltration analysis showed that antigen presentation was weak in SCLC, and TOP2A expression was negatively correlated with CD8+ T cells, while HLA-ABC expression was positively correlated with M1 macrophages, memory B cells, and CD8+ T cells. We also found that TOP2A was related to poor prognosis and inversely correlated with HLA-ABC, which was verified with immunohistochemical staining in 151 SCLC specimens. Our study findings indicated that TOP2A may be a potential prognosis indicator and a target to reverse the immunosuppressive tumor microenvironment of SCLC.

Pseudoprogression in lung cancer patients treated with immunotherapy.

Lung cancer has attracted much attention because of its high morbidity and mortality worldwide. The advent of immunotherapy approaches, especially the application of immune checkpoint inhibitors (ICIs) has dramatically changed the treatment of lung cancer, but a novel and unexpected pattern of treatment response-- pseudoprogression, has been observed simultaneously which complicates the routine clinical evaluation and management. However, manifestations of pseudoprogression vary and there are many disputes on immune-related response assessment and corresponding treatments for lung cancer. Therefore, we summarized the possible mechanisms, clinical manifestations and corresponding treatment measures of pseudoprogression in lung cancer, as well as potential methods to differentiate pseudoprogression from true tumor progression.

Combination therapy: Future directions of immunotherapy in small cell lung cancer.

Small cell lung cancer (SCLC), an aggressive and devastating malignancy, is characterized by rapid growth and early metastasis. Although most patients respond to first-line chemotherapy, the majority of patients rapidly relapse and have a relatively poor prognosis. Fortunately, immunotherapy, mainly including antibodies that target the cytotoxic T lymphocyte antigen-4 (CTLA-4), checkpoints programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) to block immune regulatory checkpoints on tumor cells, immune cells, fibroblasts cells and endothelial cells, has achieved the milestone in several solid tumors, such as melanoma and non-small-cell lung carcinomas (NSCLC). In recent years, immunotherapy has made progress in the treatment of patients with SCLC, while its response rate is relatively low to monotherapy. Interestingly, the combination of immunotherapy with other therapy, such as chemotherapy, radiotherapy, and targeted therapy, preliminarily achieve greater therapeutic effects for treating SCLC. Combining different immunotherapy drugs may act synergistically because of the complementary effects of the two immune checkpoint pathways (CTLA-4 and PD-1/PD-L1 pathways). The incorporation of chemoradiotherapy in immunotherapy may augment antitumor immune responses because chemoradiotherapy can enhance tumor cell immunogenicity by rapidly inducing tumor lysis and releasing tumor antigens. In addition, since immunotherapy drugs and the molecular targets drugs act on different targets and cells, the combination of these drugs may achieve greater therapeutic effects in the treatment of SCLC. In this review, we focused on the completed and ongoing trials of the combination therapy for immunotherapy of SCLC to find out the rational combination strategies which may improve the outcomes for SCLC.

Corrigendum: Decreased DUSP26 Expression Promotes Malignant Behavior in Glioblastoma Cells via Deregulation of MAPK and Akt Signaling Pathway.

[This corrects the article DOI: 10.3389/fonc.2021.622826.].

Decreased DUSP26 Expression Promotes Malignant Behavior in Glioblastoma Cells via Deregulation of MAPK and Akt Signaling Pathway.

PURPOSE: Dual-specificity protein phosphatases 26 (DUSP26) is a recently identified phosphatase enzyme that regulates MAPK and Akt signaling pathways. The role of DUSP26 in the development and prognosis of high-grade gliomas (HGGs) and primary glioblastoma (GBM) has remained unclear and was the focus of this study. MATERIALS AND METHODS: The prognostic value of DUSP26 was assessed using retrospective analyses using online data sets and tissue microarray of HGGs. U251 and U87 cells modified to overexpress DUSP26 were utilized to study the role of DUSP26 in cell growth, migration, and cell apoptosis analyzed by CCK-8 assay, clonogenic, transwell migration, and TUNEL, respectively. The phosphorylation of proteins in MAPK and Akt signaling pathways was assayed by Western blot and immunofluorescence assays. RESULTS: Analyses using available online data sets and tissue microarray showed that DUSP26 is down-regulated in high-grade gliomas and GBM as compared to normal brain. Stratification of glioma patients based on DUSP26 expression level showed an inverse correlation between DUSP26 expression and patient survival. At the cellular level, DUSP26 overexpression led to decreased cell proliferation, migration, and senescence in U251 and U87 cells, whereas apoptosis was increased as compared to corresponding controls. Interestingly, the biologic effects of DUSP26 overexpression were associated with the dephosphorylation of proteins in the MAPK and Akt signaling pathways. CONCLUSIONS: These findings suggest that the loss of DUSP26 expression, seen in a subset of high-grade gliomas and GBM patients, facilitates malignant behavior; and with inverse correlation between its expression levels with patient survival. DUSP26 can serve as an independent prognostic factor.

Bioinformatics analysis and experimental validation of TTK as a biomarker for prognosis in non-small cell lung cancer.

BACKGROUND: Despite the prominent development of medical technology in recent years, the prognosis of non-small cell lung cancer (NSCLC) is still not optimistic. It is crucial to identify more reliable diagnostic biomarkers for the early diagnosis and personalized therapy of NSCLC and clarify the molecular mechanisms underlying NSCLC progression. METHODS: In the present study, bioinformatics analysis was performed on three datasets obtained from the Gene Expression Omnibus to identify the NSCLC-associated differentially expressed genes (DEGs). Immunohistochemistry-based tissue microarray of human NSCLC was used to experimental validating the potential targets obtained from bioinformatics analysis. RESULTS: By using protein-protein interaction (PPI) network analysis, Kaplan-Meier plotter, and Gene Expression Profiling Interactive Analysis, we selected 40 core DEGs for further study. Then, a re-analysis of 40 selected genes via Kyoto Encyclopedia of Genes and Genomes pathway enrichment showed that nine key genes involved in the cell cycle and p53 signaling pathway participated in the development of NSCLC. Then, we checked the protein level of nine key genes by semi-quantitative of IHC and checked the distribution at a single-cell level. Finally, we validated dual-specificity protein kinase TTK as a biomarker for prognosis in a tissue microarray. High TTK expression associated with a higher histological stage, advanced TNM stage, high frequency of positive lymph nodes, and worse 5-year overall survival. CONCLUSIONS: We found nine key genes were enriched in the cell cycle and p53 signaling pathway. TTK could be considered as a potential therapeutic target and for the prognosis biomarker of NSCLC. These findings will provide new insights for the development of individualized therapeutic targets for NSCLC.