Search

To investigate the protein expression levels of cyclin‐dependent kinase subunit 2 (CKS2) and the cluster of differentiation (CD) 47 in gastric cancer (GC) and their clinical significance. A total of 126 GC patients who underwent radical resection were selected as study subjects. Additionally, 32 patients with benign gastric tumour, 42 patients with low‐grade intraepithelial neoplasia (LGIEN), and 49 patients with high‐grade intraepithelial neoplasia (HGIEN) who underwent surgery were selected as the control groups. Immunohistochemistry was used to detect the expression of CKS2 and CD47 in surgical specimens. We statistically analysed the clinical significance of the expression of the two factors. (1) The positivity rates for CKS2 in benign gastric tumour tissue, LGIEN tissue, HGIEN tissue, and GC tissue gradually increased, that is, 6.3% (2/32), 30.9% (13/42), 38.8% (19/49), and 60.3% (76/126), respectively, and the positivity rates for CD47 were 18.8% (6/32), 38.1% (16/42), 46.9% (23/49), and 65.9% (83/126), respectively. (2) High expression of CKS2 and CD47 were associated with tumour diameter, Lauren classification, number of lymph node metastases, and TNM stage. In addition, the immunohistochemical scores for CKS2 and CD47 were positively correlated (r =.625, P =.000). (3) The median follow‐up time of 126 patients was 46.5 months, and the overall survival (OS) rate was 40.5% (51/126). Survival analysis showed that compared with that in the CKS2 (−) group, the OS rate for patients in the CKS2 (+) group was significantly worse and that compared with the CD47 (−) group, the CD47 (+) group had significantly worse OS (30.1% vs 60.5%, χ2 = 15.67, P =.000). (4) The OS rates of CKS2 (+) CD47 (+) group, CKS2 (+) CD47 (−) group, CKS2 (−) CD47 (+) group, and CKS2 (−) CD47 (−) group were 20.0% (13/65), 58.3% (7/12), 57.1% (8/14), 65.7% (23/35), respectively, the prognosis of patients in CKS2 (+) CD47 (+) group was significantly poor. High expression levels of CKS2 and CD47 were closely related to the occurrence of GC and can be used as independent risk factors to assess the prognosis of patients. [ABSTRACT FROM AUTHOR]

Background: The aim of this work was to screen and validate biomarkers of ovarian cancer-initiating cells to detect the mechanisms of recurrence of epithelial ovarian cancer (EOC).Methods: Stably labelled the amino acid in side population (SP) cells of epithelial ovarian cancer which were rich in cancer-initiating cells and non-SP cells with isotope in culture and differentially expressed cellular membrane proteins in SP cells were identified through proteomics technology. The new candidate biomarker was screened and validated through RT-PCR and western blot. Both in cell lines and primary EOC, cancer-initiating biofunctions of CDC50A positive cells were validated. Moreover, the characteristics of mesenchymal transition (EMT) was also detected and the correlation between the biomarker and clinical prognosis was observed.Results: Through proteomics technology, candidate protein CDC50A was screened, and its significantly differential expression in SP cells was validated. CDC50A-positive cells from cell lines and primary ovarian cancer tissues were validated to show characteristics of cancer-initiating cells both in vitro and in vivo, including sphere-forming, self-renewal, differentiation, tumor metastasis and tumorigenicity in mice. The relationship between CDC50A-positive cells from primary tissues and tumour metastasis was confirmed based on their mesenchymal transition characteristics. Among 16 high-grade ovarian serous cancer patients, a high ratio of CDC50A-positive cells in primary tumours was correlated with a shorter platinum-free interval (p = 0.031, HR 0.260, 95% CI 0.77 ~ 0.885).Conclusion: CDC50A could be used to screen ovarian cancer-initiating cells and might be a new target to resolve tumour development in EOC patients. [ABSTRACT FROM AUTHOR]

Background: Although eukaryotic initiation factor 6 (eIF6) is a novel therapeutic target, data on its importance in the development of esophageal carcinoma (ESCA) remains limited. This study evaluated the correlation between eIF6 expression and metabolic analysis using fluorine-18 fluorodeoxyglucose (18F-FDG) -Positron emission tomography (PET) and immune gene signatures in ESCA.Methods: This study employed The Cancer Genome Atlas (TCGA) to analyze the expression and prognostic value of eIF6, as well as its relationship with the immune gene signatures in ESCA patients. The qRT-PCR and Western blot analyses were used to profile the expression of eIF6 in ESCA tissues and different ESCA cell lines. The expression of tumor eIF6 and glucose transporter 1 (GLUT1) was examined using immunohistochemical tools in fifty-two ESCA patients undergoing routine 18F-FDG PET/CT before surgery. In addition, the cellular responses to eIF6 knockdown in human ESCA cells were assessed via the MTS, EdU, flow cytometry and wound healing assays.Results: Our data demonstrated that compared with the normal esophageal tissues, eIF6 expression was upregulated in ESCA tumor tissues and showed a high diagnostic value with an area under curve of 0.825 for predicting ESCA. High eIF6 expression was significantly correlated with shorter overall survival of patients with esophagus adenocarcinoma (p = 0.038), but not in squamous cell carcinoma of the esophagus (p = 0.078). In addition, tumor eIF6 was significantly associated with 18F-FDG PET/CT parameters: maximal and mean standardized uptake values (SUVmax and SUVmean) and total lesion glycolysis (TLG) (rho = 0.458, 0.460, and 0.300, respectively, p < 0.01) as well as GLUT1 expression (rho = 0.453, p < 0.001). A SUVmax cutoff of 18.2 led to prediction of tumor eIF6 expression with an accuracy of 0.755. Functional analysis studies demonstrated that knockdown of eIF6 inhibited ESCA cell growth and migration, and fueled cell apoptosis. Moreover, the Bulk RNA gene analysis revealed a significant inverse association between eIF6 and the tumor-infiltrating immune cells (macrophages, T cells, or Th1 cells) and immunomodulators in the ESCA microenvironment.Conclusion: Our study suggested that eIF6 might serve as a potential prognostic biomarker associated with metabolic variability and immune gene signatures in ESCA tumor microenvironment. [ABSTRACT FROM AUTHOR]

Distant metastasis is the main cause of death in patients with clear cell renal carcinoma (ccRCC). The dysregulation of the tumor microenvironment is responsible for tumorigenesis and metastasis in ccRCC. The role of long non-coding RNAs in the tumor immune of ccRCC remains unclear. The present study screened differentially expressed protein-coding genes and non-coding genes between ccRCC and normal tissues based on three datasets. The commonly deregulated genes were used to identify distant metastasis-related long non-coding RNAs (lncRNAs) and prognostic lncRNAs. Pearson correlation analysis was used to identify immune-related lncRNAs. A competing endogenous RNA network was constructed and hub lncRNAs were identified. A total of 1650 coding genes, 821 lncRNAs and 62 miRNAs were commonly deregulated in the three datasets. A total of 408 lncRNAs associated with the overall survival of patients with ccRCC were identified. Among them, 82 lncRNAs were distant metastasis-related. Further analysis identified 52 lncRNAs associated with the immune pathway. Functional analyses concordantly demonstrated the role of the 52 lncRNAs in metastasis and tumor immunology. The ceRNA network analysis indicated lncRNA DSCR9 as the key lncRNA regulator. Univariate and multivariate analysis in two independent cohorts validated that DSCR9 could be an independent risk factor for the progression-free survival of patients with ccRCC. Further analyses indicated that DSCR9 might be associated with the immunotherapeutic response. reverse transcription-quantitative PCR demonstrated that the RNA expression level of DSCR9 was upregulated in ccRCC compared with normal kidney samples. The present study demonstrated the potential of LncRNA DSCR9 in assessing the prognosis and developing future immunotherapy for patients with metastatic ccRCC. [ABSTRACT FROM AUTHOR]

Objective: To explore the histopathological characteristics of paired recurrent gliomas and their clinical significance. Methods: Glioma patients who received both primary surgery and reoperation when recurrence at Sun Yat-sen University Cancer Center from June 2001 to June 2019 were enrolled. Clinical and pathological characteristics were analyzed retrospectively, and histopathology of reoperation specimens was divided into three categories according to tumor cell activity and the degree of necrosis: active group, low-activity group, and necrosis group. Results: A total of 89 patients were included in this study. The 2016 WHO grade of the first operation pathology and IDH1 status were related to survival time after the first operation, but there was no significant association with survival time after reoperation. The time interval between primary and reoperation was shorter for primary high-grade glioma and/or IDH1 wild-type tumor patients than for low-grade glioma and/or IDH1 mutant tumor patients (P < 0.001). Histopathological types of recurrent gliomas were analyzed, and 67 cases (75.3%) were classified into the active group, 14 (15.8%) into the low-activity group, and 8 (8.9%) into the necrosis group. The low-activity or necrosis group was associated with a higher radiotherapy dose and shorter operation interval. Further univariate and multivariate Cox survival analyses showed the histopathological patterns of recurrent gliomas to be related to survival time after reoperation. Conclusion: Primary WHO low grade or IDH1 mutant gliomas appeared survival benefit mainly on later recurrence, but was not a prognostic predictor following recurrence. Histopathological feature of recurrent glioma is related to previous treatment, including radiotherapy dosage and chemotherapy treatment, and is also an important independent prognostic factor for patients after reoperation. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma (GBM) is the most common malignant brain tumor in adults and is associated with a poor prognosis. Cytotoxic T lymphocyte antigen -4 (CTLA-4) blocking antibodies have demonstrated an ability to generate robust antitumor immune responses against a variety of solid tumors. 4-1BB (CD137) is expressed by activated T lymphocytes and served as a co-stimulatory signal, which promotes cytotoxic function. Here, we evaluate a combination immunotherapy regimen involving 4-1BB activation, CTLA-4 blockade, and focal radiation therapy in an immune-competent intracranial GBM model. Methods: GL261-luciferace cells were stereotactically implanted in the striatum of C57BL/6 mice. Mice were treated with a triple therapy regimen consisted of 4-1BB agonist antibodies, CTLA-4 blocking antibodies, and focal radiation therapy using a small animal radiation research platform and mice were followed for survival. Numbers of brain-infiltrating lymphocytes were analyzed by FACS analysis. CD4 or CD8 depleting antibodies were administered to determine the relative contribution of T helper and cytotoxic T cells in this regimen. To evaluate the ability of this immunotherapy to generate an antigen-specific memory response, long-term survivors were re-challenged with GL261 glioma en B16 melanoma flank tumors. Results: Mice treated with triple therapy had increased survival compared to mice treated with focal radiation therapy and immunotherapy with 4-1BB activation and CTLA-4 blockade. Animals treated with triple therapy exhibited at least 50% long-term tumor free survival. Treatment with triple therapy resulted in a higher density of CD4+ and CD8+ tumor infiltrating lymphocytes. Mechanistically, depletion of CD4+ T cells abrogated the antitumor efficacy of triple therapy, while depletion of CD8+ T cells had no effect on the treatment response. Conclusion: Combination therapy with 4-1BB activation and CTLA-4 blockade in the setting of focal radiation therapy improves survival in an orthotopic mouse model of glioma by a CD4+ T cell dependent mechanism and generates antigen-specific memory. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the factors that influence the prognosis of swallowing function rehabilitation therapy in patients with dysphagia after medullary infarction. Patients and Methods: This retrospective study was conducted using the clinical data of 51 patients who were diagnosed with dysphagia after medullary infarction and hospitalized at our institution between January 2019 and January 2021. As per the water swallow test (WST) grade at 1 month after rehabilitation treatment, patients were classified into the good prognosis group and the poor prognosis group. Univariate analysis as well as univariate and multivariate logistic regression analysis were used to analyze factors that influence the prognosis of swallowing function rehabilitation therapy in patients with dysphagia after medullary infarction. Receiver operating characteristic (ROC) curves were then used to test the predictive ability of the significant parameters to predict the prognosis of the rehabilitation therapy in these patients. Results: Univariate analysis and univariate logistic regression analysis showed that previous stroke (odds ratio [OR] = 1.361), dysarthria (OR = 3.771), disease course (OR = 1.112), National Institutes of Health Stroke Scale (NIHSS) score at admission (OR = 2.596), and infarct site (OR = 11.071) were all significantly correlated with the prognosis of swallowing function rehabilitation therapy in patients with dysphagia after medullary infarction (P < 0.05). Multivariate logistic regression analysis showed that dysarthria (OR = 5.519, 95% confidence interval (CI) 1.413– 21.566), infarct site (OR = 18.634, 95% CI 1.696– 204.73), and the NIHSS score (OR = 1.001, 95% CI 1.536– 4.820) were independent influencing factors of the prognosis of swallowing function rehabilitation therapy in these patients. The ROC curve showed that the area under the curve for the combined prediction of the three indicators was 0.943. Conclusion: The NIHSS score, dysarthria, and infarct site are independent influencing factors for the prognosis of swallowing function rehabilitation therapy in patients with dysphagia after medullary infarction. [ABSTRACT FROM AUTHOR]

Background: Since progressive intracranial haemorrhage (PIH) was introduced in neurosurgical literatures, several studies have been performed. PIH has been shown to be associated with a high increase in the risk of clinical worsening and related to morbidity and mortality as well. So, early detection and prediction of PIH is practically important in a clinical situation. Objectves: To investigate the risk factors related to PIH in patients with acute traumatic brain injury (TBI) and analyse their clinical significances. Methods: PIH was confirmed by comparing the first and repeated CT scans. Data compared included gender, age, mechanism of injury, Glasgow Coma Score (GCS) at admission, timing from injury to the first CT, the signs of the initial CT scan, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fg), thrombin time (TT), platelet (PLT) and D-dimer (D-D) values. Logistic regression analysis was used to show the risk factors related to PIH. Results: A cohort of 498 patients with TBI was evaluated, and there were 139 (27.91%) patients who suffered from PIH. The differences between PIHs and non-PIHs were significant in age, GCS at admission, the signs of the initial CT scan (fracture, subarachnoid haemorrhage, brain contusion and primary haematoma), PT, Fg and D-D values ( p < 0.001). Logistic regression analysis was used to identify that CT scans (subarachnoid haemorrhage, brain contusion and primary haematoma) and plasma D-D values as the most important predictors of PIH ( p < 0.001). Conclusions: For patients with the initial CT scan showing subarachnoid haemorrhage, brain contusion and primary haematoma with abnormal D-D levels, an earlier and dynamic CT scan should be performed, for the detection of PIH as early as possible and the medical intervention would be enforced in time. [ABSTRACT FROM AUTHOR]

Background: Large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma among adults. In some cases, DLBCL may seem similar to carcinoma cells, presenting a round, oval, or polygonal shape and clear nuclei. We found that the expression of P63 accounted for a considerable proportion of DLBCL cases. Under the circumstances, P63 expression may lead to a misdiagnosis, especially with a small biopsy. We aim to investigate the expression status and prognostic significance of P63 in a cohort of Chinese DLBCL patients. Methods: P63, ΔNP63(P40), P53 and Ki67 were detected by immunohistochemistry (IHC). A ROC curve was adopted to find the best cut-off value for positive P63/P53 expression and high Ki67 expression. We defined P53 as positive when ≥50% of the tumor cells showed staining. The relationship between P63 and P53/Ki67 expression was examined. Time-to-event endpoints were estimated according to the Kaplan-Meier method. Moreover, multivariate analyses were conducted to evaluate the prognostic factors in DLBCL. Results: Out of all the 159 DLBCL cases, 76 (47.8%) expressed P63 in the nuclei, while 41 (25.8%) were determined to have high expression by using a ROC cut-off value "≥6". Examination of the different P63 isoforms revealed that the ΔNP63(P40) was unclearly and weakly expressed in only 3 cases, showing a fuzzy yellow cytoplasm. P63 expression was not correlated with subtype (GCB or non-GCB) or P53 but was correlated with a high proliferative index (Ki67). Kaplan-Meier analyses revealed that P63 expression was correlated with overall survival, and P63 positive cases showed poor survival outcomes (P<0.05) in our cohort. Conclusions: ΔNP63(P40) is a useful marker in the differential diagnosis of poorly differentiated squamous cell carcinoma versus DLBCL in small needle biopsy. P63 may be involved in DLBCL tumor progression, and it is an unfavorable prognostic marker in DLBCL. A subgroup of P63 and P53 coexpression DLBCL patients with an extremely poor prognosis should be noted. [ABSTRACT FROM AUTHOR]

Abstract Malignant tumors of the digestive tract include esophageal, gastric, and colorectal carcinomas, which all have high global mortality rates. A clinical role for small nuclear RNA (snRNA), a type of small non-coding RNA, has not yet been documented for digestive tract pan-adenocarcinomas. Therefore, the aim of the study was to identify differentially expressed snRNAs and to explore their prognostic implications in pan-adenocarcinomas from the esophagus, stomach, colon, and rectum. The pan-carcinoma RNA-sequencing data of four types of digestive tract cancers with 1, 102 cases obtained from The Cancer Genome Atlas (TCGA) project were analyzed and the differentially expressed snRNAs were evaluated using the edgeR package. The prognostic value of each of the selected snRNAs was determined by univariate and multivariate Cox regression analyses. All the digestive tract pan-adenocarcinomas showed differential expression of three snRNAs: the up-regulated RNU1-106 P and RNU6-850 P and the down-regulated RNU6-529 P. Interestingly, RNU6-101 P appeared to be a risk factor for esophageal adenocarcinoma (ESAD) and RNVU1-4 was potentially a protective factor for stomach adenocarcinoma (STAD) survival. This consistent finding of differential expression of all three snRNAs in all four types of digestive system cancers suggests potential roles for these snRNAs in the tumorigenesis of digestive system cancers. RNU6-101 P could play a pivotal role in the progression of ESAD and RNVU1-4 could perform a protective role in STAD. However, since the current findings were based on RNA-sequencing data mining, more studies are needed for verification. [ABSTRACT FROM AUTHOR]

Background: Since colorectal cancer (CRC) is one of the most common malignant tumors worldwide, we aimed to identify the role of sex determining region Y (SRY)-box 18 (SOX18) in CRC. Methods: RT-PCR and immunohistochemistry were employed to detect the expression of SOX18 in CRC samples. We then identified the effect of SOX18 on cell proliferation, cell cycle, and apoptosis by cell counting kit-8 (CCK-8), flow cytometry, and annexin V/PI staining, respectively. The effect of silencing SOX18 expression in CRC development was evaluated by using a xenograft mouse model. Results: First, we found that SOX18 was overexpressed in CRC tissues and cell lines and that SOX18 levels in CRC tissues were positively associated with advanced clinical stages, vascular invasion, and lymph node metastasis. Furthermore, patients with higher expression of SOX18 had a lower survival rate. Overexpression of SOX18 significantly promoted cell proliferation, promoted S cell cycle progression, and inhibited cell apoptosis. Conversely, downregulation of SOX18 clearly weakened cell proliferation, induced G0/G1 cell cycle phase arrest, and gave rise to cell apoptosis. The results showed that shSOX18 significantly inhibited tumor growth and weight. Ki67 expression was also decreased by SOX18 silencing treatment. Conclusion: Our study indicates that SOX18 may have a carcinogenic effect on CRC, which might provide novel insights into CRC prevention and treatment. [ABSTRACT FROM AUTHOR]

Background Prolyl 4-Hydroxylase Subunit Alpha 1 (P4HA1) is the active catalytic component of prolyl 4-hydroxylase and plays a crucial role in modulating extracellular matrix hemostasis. P4HA1 has been reported to promote tumor progression by enhancing invasion and angiogenesis. Overexpression of P4HA1 is associated with decreased survival for patients with breast and prostate cancer. However, the prognostic significance of P4HA1 for glioma patients remains undefined. Methods The expression of P4HA1 in 290 gliomas (WHO grade II–IV) and 10 normal brain tissues was examined with TMA-based immunohistochemistry assay. The correlation between P4HA1 expression and clinicopathological parameters as well as the prognosis of glioma patients was investigated. Results Cytoplasmic expression of P4HA1 is high in 37.93% of all glioma cases, with 44.98% in high-grade gliomas and 19.75% in low-grade gliomas respectively. Increased P4HA1 level was correlated with advanced histological grade ( p < 0.01) and old age ( p = 0.01). Upregulation of P4HA1, as well as histological grade, was an independent risk factor for unfavorable prognosis. Subgroup analysis demonstrated that high P4HA1 expression was significantly associated with poor prognosis for high-grade gliomas ( p < 0.01) but not for low-grade gliomas. Conclusions P4HA1 was upregulated in gliomas. High expression of P4HA1 was correlated with the malignancy of gliomas and could serve as a prognostic indicator for patients with high-grade gliomas. [ABSTRACT FROM AUTHOR]

Purpose: For inoperable stage I (T1-T2N0) small cell lung cancer (SCLC), national guidelines recommend chemotherapy with or without conventionally fractionated radiation therapy. The present multi-institutional cohort study investigated the role of stereotactic ablative radiation therapy (SABR) for this population.Methods and Materials: The clinical and treatment characteristics, toxicities, outcomes, and patterns of failure were assessed in patients with histologically confirmed stage T1-T2N0M0 SCLC. Kaplan-Meier analysis was used to evaluate the survival outcomes. Univariate and multivariate analyses identified predictors of outcomes.Results: From 24 institutions, 76 lesions were treated in 74 patients (median follow-up 18 months). The median age and tumor size was 72 years and 2.5 cm, respectively. Chemotherapy and prophylactic cranial irradiation were delivered in 56% and 23% of cases, respectively. The median SABR dose and fractionation was 50 Gy and 5 fractions. The 1- and 3-year local control rate was 97.4% and 96.1%, respectively. The median disease-free survival (DFS) duration was 49.7 months. The DFS rate was 58.3% and 53.2% at 1 and 3 years, respectively. The median, 1-year, and 3-year disease-specific survival was 52.3 months, 84.5%, and 64.4%, respectively. The median, 1-year, and 3-year overall survival (OS) was 17.8 months, 69.9%, and 34.0% respectively. Patients receiving chemotherapy experienced an increased median DFS (61.3 vs 9.0 months; P=.02) and OS (31.4 vs 14.3 months; P=.02). The receipt of chemotherapy independently predicted better outcomes for DFS/OS on multivariate analysis (P=.01). Toxicities were uncommon; 5.2% experienced grade ≥2 pneumonitis. Post-treatment failure was most commonly distant (45.8% of recurrence), followed by nodal (25.0%) and "elsewhere lung" (20.8%). The median time to each was 5 to 7 months.Conclusions: From the findings of the largest report of SABR for stage T1-T2N0 SCLC to date, SABR (≥50 Gy) with chemotherapy should be considered a standard option. [ABSTRACT FROM AUTHOR]

DEAH-box helicase 33 (DHX33) has been implicated in ribosome biogenesis, mRNA translation and inflammation. However, the role of DHX33 in human cancer is rarely studied. Here, we showed that DHX33 expression was significantly increased in hepatocellular carcinoma (HCC), compared with the adjacent nontumorous tissues. In a cohort of 520 patients, DHX33 expression in HCC was closely associated with tumor size ( P = 0.007), serum AFP level ( P = 0.011), and tumor capsule ( P = 0.030). Kaplan–Meier analysis indicated high DHX33 expression was correlated with worse overall and disease-free survival, and higher recurrence rate. The prognostic value of DHX33 was further confirmed by stratified survival analysis. Multivariate analysis revealed DHX33 as an independent prognostic factor for poor overall survival (Hazard Ratio = 1.772, 95% confident interval: 1.451–2.165, P < 0.0001). Our data therefore suggest DHX33 is overexpressed in HCC and serves as a promising prognostic biomarker for this deadly disease. [ABSTRACT FROM AUTHOR]

Summary: Background: MicroRNAs (miRNAs) can be used as prognostic biomarkers in many types of cancer. We aimed to identify miRNAs that were prognostic in patients with nasopharyngeal carcinoma. Methods: We retrospectively analysed miRNA expression profiles in 312 paraffin-embedded specimens of nasopharyngeal carcinoma from Sun Yat-sen University Cancer Center (Guangzhou, China) and 18 specimens of non-cancer nasopharyngitis. Using an 873 probe microarray, we assessed associations between miRNA signatures and clinical outcome in a randomly selected 156 samples (training set) and validated findings in the remaining 156 samples (internal validation set). We confirmed the miRNAs signature using quantitative RT-PCR analysis in 156 samples from a second randomisation of the 312 samples, and validated the miRNA signature in 153 samples from the West China Hospital of Sichuan University in Chengdu, China (independent set). We used the Kaplan-Meier method and log-rank tests to estimate correlations of the miRNA signature with disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival. Findings: 41 miRNAs were differentially expressed between nasopharyngeal carcinoma and non-cancer nasopharyngitis tissues. A signature of five miRNAs, each significantly associated with DFS, was identified in the training set. We calculated a risk score from the signature and classified patients as high risk or low risk. Compared with patients with low-risk scores, patients with high risk scores in the training set had shorter DFS (hazard ratio [HR] 2·73, 95% CI 1·46–5·11; p=0·0019), DMFS (3·48, 1·57–7·75; p=0·0020), and overall survival (2·48, 1·24–4·96; p=0·010). We noted equivalent findings in the internal validation set for DFS (2·47, 1·32–4·61; p=0·0052), DMFS (2·28, 1·09–4·80; p=0·030), and overall survival (2·87, 1·38–5·96; p=0·0051) and in the independent set for DFS (3·16, 1·65–6·04; p=0·0011), DMFS (2·39, 1·05–5·42; p=0·037), and overall survival (3·07, 1·34–7·01; p=0·0082). The five-miRNA signature was an independent prognostic factor. A combination of this signature and TNM stage had better prognostic value than did TNM stage alone in the training set (area under receiver operating characteristics 0·68 [95% CI 0·60–0·76] vs 0·60 [0·52–0·67]; p=0·013), the internal validation set (0·70 [0·61–0·78] vs 0·61 [0·54–0·68]; p=0·012), and the independent set (0·70 [0·62–0·78] vs 0·63 [0·56–0·69]; p=0·032). Interpretation: Identification of patients with the five-miRNA signature might add prognostic value to the TNM staging system and inform treatment decisions for patients at high risk of progression. Funding: Science Foundation of Chinese Ministry of Health, National Natural Science Foundation of China, Pearl River Scholar Funded Scheme, Guangdong Key Scientific and Technological Innovation Program, Guangdong Natural Science Foundation, Fundamental Research Funds for the Central Universities. [Copyright &y& Elsevier]

Background: Breast cancer metastasis suppressor 1 (BRMS1) is a metastasis suppressor gene. This study aimed to investigate the impact of BRMS1 on metastasis in nasopharyngeal carcinoma (NPC) and to evaluate the prognostic significance of BRMS1 in NPC patients. Methods: BRMS1 expression was examined in NPC cell lines using quantitative reverse transcription-polymerase chain reaction and Western blotting. NPC cells stably expressing BRMS1 were used to perform wound healing and invasion assays in vitro and a murine xenograft assay in vivo. Immunohistochemical staining was performed in 274 paraffin-embedded NPC specimens divided into a training set (n = 120) and a testing set (n = 154). Results: BRMS1 expression was down-regulated in NPC cell lines. Overexpression of BRMS1 significantly reversed the metastatic phenotype of NPC cells in vitro and in vivo. Importantly, low BRMS1 expression was associated with poor distant metastasis-free survival (DMFS, P < 0.001) and poor overall survival (OS, P < 0.001) in the training set; these results were validated in the testing set and overall patient population. Cox regression analysis demonstrated that low BRMS1 expression was an independent prognostic factor for DMFS and OS in NPC. Conclusions: Low expression of the metastasis suppressor BRMS1 may be an independent prognostic factor for poor prognosis in NPC patients. [ABSTRACT FROM AUTHOR]

Background: Ependymal tumors are pathologically defined intrinsic neoplasms originating in the intracranial compartments or the spinal cord that affect both children and adults. The recently integrated classification of ependymomas based on both histological and molecular characteristics is capable of subgrouping patients with various prognoses. However, the application of histological and molecular markers in Chinese patients with ependymomas has rarely been reported. We aimed to demonstrate the significance of histological characteristics, the v-relavian reticuloendotheliosis viral oncogene homolog A (RELA) fusions and other molecular features in ependymal tumors.Methods: We reviewed the histological characteristics of ependymal tumors using conventional pathological slides and investigate the RELA fusions and Cylclin D1 (CCND1) amplification by Fluorescence in situ hybridization (FISH) and trimethylation of histone 3 lysine 27 (H3K27me3) expression by immunohistochemistry (IHC) methods. SPSS software was used to analyze the data.Results: We demonstrated that hypercellularity, atypia, microvascular proliferation, necrosis, mitosis, and an elevated Ki-67 index, were tightly associated with an advanced tumor grade. Tumor location, necrosis, mitosis and the Ki-67 index were related to the survival of the ependymomas, but Ki67 was the only independent prognostic factor. Additionally, RELA fusions, mostly presented in pediatric grade III intracranial ependymomas, indicated decreased survival times of patients, and closely related to the patients' age, tumor grade, cellularity, cellular atypia, necrosis and Ki67 index in the intracranial ependymal tumors, whereas reduction of H3K27me3 predicted the worse prognosis in ependymal tumors.Conclusions: Histological and molecular features facilitate tumor grading and prognostic predictions for ependymal tumors in Chinese patients. [ABSTRACT FROM AUTHOR]