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Sex-determining region Y-related high mobility group box 4 (SOX4) has been proven to serve as a critical role in cancer development and progression. However, little is known about the pathological role of SOX4 in breast cancer patients. The purpose of this study is to measure the expression of SOX4 in breast cancer patients and to explore the clinical significance of SOX4. Using RT-PCR and Western blot, messenger RNA (mRNA) and protein expression of SOX4 were measured in breast cancer tissues and adjacent normal mammary tissues. The relationship of SOX4 expression with clinical characteristics of 148 breast cancer patients was analyzed by immunohistochemistry. In the present study, our results indicated that SOX4 mRNA and protein were highly expressed in breast cancer tissues compared with adjacent normal mammary tissues and positively correlated with clinical stage (I-II vs. III-IV; P = 0.008), T classification (T1-T2 vs. T3-T4; P = 0.013), N classification (N0-N1 vs. N2-N3; P < 0.001), M classification (M0 vs. M1; P = 0.001), estrogen receptor (negative vs. positive; P = 0.029), progesterone receptor (negative vs. positive; P = 0.004), and histological grade (G1 vs. G2-G3; P = 0.033) in breast cancer patients. Furthermore, we also found that SOX4 protein overexpression was an unfavorable prognostic factor in breast cancer patients (P < 0.001), regardless of clinical stage, tumor size, lymph node metastasis, and distant metastasis. Finally, high SOX4 expression was an independent poor prognostic factor for pancreatic patients through multivariate analysis (P = 0.033). In conclusion, SOX4 overexpression serves as an unfavorable prognostic biomarker in breast cancer patients.

Abstract Objective This cross‐sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID‐19 in China. Methods This study was conducted by 45 tertiary Grade‐A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID‐19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self‐reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions The incidence of dysosmia and dysgeusia following infection with the SARS‐CoV‐2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS‐CoV‐2 vaccination, history of head‐facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

Abstract Purpose To investigate the clinical characteristics of nasopharyngeal carcinoma (NPC) and a concomitant hepatitis B virus (HBV) infection, as well as the potential effects of HBV infection and antiviral therapy on prognosis. Methods We conducted a retrospective chart review of all NPC patients from December 2010 to December 2014. After collecting medical records and conducting follow‐ups on patients, a total of 876 eligible NPC patients were included. For each patient, medical records were reviewed. Factors predictive of outcome were compared using the log‐rank test and Cox regression analysis. Results Among the 876 participants, 106 (12.1%) patients were HBV‐infected patients. The hepatitis B surface antigen‐positive [HBsAg(+)] group had a lower CD4+ T cell count than the HBsAg(−) group (P = .048). Among patients with stage I/II NPC, 5‐year overall survival (OS), disease‐free survival (DFS), relapse‐free survival, and distant metastasis‐free survival (DMFS) of the HBsAg(+) group were 82.5%, 70.7%, 87.7%, and 76.6%, respectively, whereas those of the HBsAg(−) group were 91.4%, 86.0%, 93.8%, and 92.1%, respectively. Statistically significant differences in OS, DFS, and DMFS existed between both groups (P = .017, .018, and .004, respectively). The multivariate analysis indicated that HBsAg status and N stage are independent risk factors affecting OS, DFS, and DMFS of NPC patients. A statistically significant difference in 5‐year DMFS existed between the antivirus (90.0%) and no‐antivirus groups (70.0%) (P = .043). Conclusions Hepatitis B virus infection is an independent risk factor for early stage NPC, which may be associated with its reduced immune functions compared to the HBsAg(−) group. Anti‐HBV treatment may improve the prognosis of HBV‐infected NPC patients.

Background: Nonalcoholic steatohepatitis (NASH)-driven hepatocellular carcinoma (HCC) is becoming a major health-related problem. The exploration of NASH-related prognostic biomarkers and therapeutic targets is necessary. Methods: Data were downloaded from the GEO database. The "glmnet" package was used to identify differentially expressed genes (DEGs). The prognostic model was constructed by the univariate Cox and LASSO regression analyses. Validation of the expression and prognosis by immunohistochemistry (IHC) in vitro. Drug sensitivity and immune cell infiltration were analyzed by CTR-DB and ImmuCellAI. Results: We constructed a prognostic model that identified the NASH-related gene set (DLAT, IDH3B, and MAP3K4), which was validated in a real-world cohort. Next, seven prognostic transcription factors (TFs) were identified. The prognostic ceRNA network included three mRNAs, four miRNAs, and seven lncRNAs. Finally, we found that the gene set was associated with drug response which was validated in six clinical trial cohorts. Moreover, the expression level of the gene set was inversely correlated with CD8 T cell infiltration in HCC. Conclusions: We established a NASH-related prognostic model. Upstream transcriptome analysis and the ceRNA network provided clues for mechanism exploration. The mutant profile, drug sensitivity, and immune infiltration analysis further guided precise diagnosis and treatment strategies. [ABSTRACT FROM AUTHOR]

Objective: Glioblastoma multiforme (GBM) is the most malignant primary brain tumor in adults. This study aimed to identify significant prognostic biomarkers related to GBM. Methods: We collected 3 GBM and 3 healthy human brain samples for transcriptome and proteomic sequencing analysis. Differentially expressed genes (DEGs) between GBM and control samples were identified using the edge R package in R. Functional enrichment analyses, prediction of long noncoding RNA target genes, and protein-protein interaction network analyses were performed. Subsequently, transcriptomic and proteomic association analyses, validation using The Cancer Genome Atlas (TCGA) database, and survival and prognostic analyses were conducted. Then the hub genes directly related to GBM were screened. Finally, the expression of key genes was verified by quantitative polymerase chain reaction (qPCR). Results: Totally, 1140 transcripts and 503 proteins were significantly up- or down-regulated. A total of 25 genes were upregulated and 62 were downregulated at both the transcriptome and proteome levels. Results from TCGA database showed that 84 of these 87 genes matched with transcriptome sequencing results. A Cox regression analysis suggested that Fibronectin 1(FN1) was a prognostic risk factor. The qPCR results showed that FN1 was significantly upregulated in GBM samples. Conclusions: FN1 may play a role in GBM progression through ECM-receptor interaction and PI3K-Akt signaling pathways. FN1 may be considered as a prognostic biomarkers related to GBM. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate the effect of hypothyroidism and thyroxine replacement therapy on the prognosis of nasopharyngeal carcinoma (NPC) patients. Methods: The clinical data of 284 NPC patients, who received intensity‐modulated radiation therapy (IMRT) between January 2011 and December 2016, were retrospectively analyzed. Results: Hypothyroidism occurred in 38% of patients. Patients with hypothyroidism had significantly better disease‐free survival (DFS) (p = 0.002) and relapse‐free survival (RFS) (p = 0.008). Multivariate analysis showed that hypothyroidism was a positive independent prognostic factor (DFS and RFS). Among the patients with hypothyroidism, thyroxine replacement therapy did not yield inferior survival (DFS, RFS, all p > 0.05). Conclusions: The NPC patients with complete response are at risk of hypothyroidism, which is attributable to escalating dose. These patients experienced clinical hypothyroidism could be adequately treated with thyroid hormone replacement. Further investigation of the underlying biological mechanism and potential therapeutic implications are required. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) is a common subtype of lung cancer with high recurrence rate and fatality. Circ_0001361 has been recognized as key regulators in various malignancies, but its roles in LUAD remain ambiguous. Methods: Circ_0001361, miR-525-5p, and VMA21 levels were assessed by RT-qPCR. The growth and metastasis of LUAD cells were detected by MTT, colony formation, wound scratch, and transwell assays, respectively. The interaction between circ_0001361/VMA21 and miR-525-5p was detected by dual luciferase, RNA immunoprecipitation, and RNA pull-down assays. VMA21 protein level was detected by Western blotting. Nude mouse xenograft model was established to determine the role of circ_0001361 in tumor growth in vivo. Results: Circ_0001361 was up-regulated, while miR-525-5p was down-regulated in LUAD tissues and cells. Functional experiments demonstrated that circ_0001361 drove LUAD cell growth and metastasis. Mechanistically, circ_0001361 functioned as a sponge of miR-525-5p to up-regulate downstream target VMA21 level. MiR-525-5p/VMA21 axis was involved in circ_0001361-mediated malignant phenotypes of LUAD cells. Finally, inhibition of circ_0001361 restrained in vivo xenograft tumor growth via regulating miR-525-5p/VMA21 axis. Conclusion: Our findings elucidate that circ_0001361 facilitates the tumorigenesis and development of LUAD through miR-525-5p/VMA21 axis, providing evidence for circ_0001361 as a potential prognosis biomarker and therapeutic target for clinical treatment of LUAD. [ABSTRACT FROM AUTHOR]

Purpose: Glioblastoma multiforme (GBM) is the most widely occurring brain malignancy. It is modulated by a variety of genes, and patients with GBM have a low survival ratio and an unsatisfactory treatment effect. The irregular regulation of RNA binding proteins (RBPs) is implicated in several malignant neoplasms and reported to exhibit an association with the occurrence and development of carcinoma. Thus, it is necessary to build a stable, multi-RBPs signature-originated model for GBM prognosis and treatment response prediction. Methods: Differentially expressed RBPs (DERBPs) were screened out based on the RBPs data of GBM and normal brain tissues from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Program (GTEx) datasets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses on DERBPs were performed, followed by an analysis of the Protein-Protein Interaction network. Survival analysis of the DERBPs was conducted by univariate and multivariate Cox regression. Then, a risk score model was created on the basis of the gene signatures in various survival-associated RBPs, and its prognostic and predictive values were evaluated through Kaplan-Meier analysis and log-rank test. A nomogram on the basis of the hub RBPs signature was applied to estimate GBM patients' survival rates. Moreover, western blot was for the detection of the proteins. Results: BICC1, GNL3L, and KHDRBS2 were considered as prognosis-associated hub RBPs and then were applied in the construction of a prognostic model. Poor survival results appeared in GBM patients with a high-risk score. The area under the time-dependent ROC curve of the prognostic model was 0.723 in TCGA and 0.707 in Chinese Glioma Genome Atlas (CGGA) cohorts, indicating a good prognostic model. What was more, the survival duration of the high-risk group receiving radiotherapy or temozolomide chemotherapy was shorter than that of the low-risk group. The nomogram showed a great discriminating capacity for GBM, and western blot experiments demonstrated that the proteins of these 3 RBPs had different expressions in GBM cells. Conclusion: The identified 3 hub RBPs-derived risk score is effective in the prediction of GBM prognosis and treatment response, and benefits to the treatment of GBM patients. [ABSTRACT FROM AUTHOR]

In this era of precision medicine, with the help of biomarkers, immunotherapy has significantly improved prognosis of many patients with malignant tumor. Deficient mismatch repair (dMMR)/microsatellite instability (MSI) status is used as a biomarker in clinical practice to predict favorable response to immunotherapy and prognosis. MSI is an important characteristic which facilitates mutation and improves the likelihood of a favorable response to immunotherapy. However, many patients with dMMR/MSI still respond poorly to immunotherapies, which partly results from intratumor heterogeneity propelled by dMMR/MSI. In this review, we discuss how dMMR/MSI facilitates mutations in tumor cells and generates intratumor heterogeneity, especially through type II interferon (IFN-γ) signaling and tumor-infiltrating lymphocytes (TILs). We discuss the mechanism of immunotherapy from the perspective of dMMR/MSI, molecular pathways and TILs, and we discuss how intratumor heterogeneity hinders the therapeutic effect of immunotherapy. Finally, we summarize present techniques and strategies to look at the tumor as a whole to design personalized regimes and achieve favorable prognosis. [ABSTRACT FROM AUTHOR]

Rectal cancer (RC) is the leading cause of tumor-related death among both men and women. The efficacy of immunotherapy for rectal cancer is closely related to the immune infiltration level. The N6-methyladenosine (m6A) modification may play a pivotal role in tumor-immune interactions. However, the roles of m6A-related genes in tumor-immune interactions of rectal cancer remain largely unknown. After an evaluation on the expression levels of m6A-related genes and their correlations with the prognosis of rectal cancer patients, we found that METTL14 was the only gene to be significantly correlated with prognosis in rectal cancer patients. Therefore, we further observed the impact of METTL14 expression and m6A modification on the immune infiltration in rectal cancer. Our study indicates that low expression of the m6A "writer" gene METTL14 in rectal cancer may lead to the downregulation of m6A RNA modification, thus reducing the level of immune cell infiltration and resulting in poor prognosis. METTL14 expression level is an independent prognostic factor in rectal cancer and is positively correlated with the immune infiltration level. Our study identified METTL14 as a potential target for enhancing immunotherapy efficacy in rectal cancer. [ABSTRACT FROM AUTHOR]

Background: Although many biomarkers have been reported for detecting glioma, the prognosis for the disease remains poor, and therefore, new biomarkers need to be identified. GNG5, which is part of the G-protein family, has been associated with different malignant tumors, though the role of GNG5 in glioma has not been studied. Therefore, we aimed to identify the relationship between GNG5 and glioma prognosis and identify a new biomarker for the diagnosis and treatment of gliomas. Methods: We used data on more than a thousand gliomas from multiple databases and clinical data to determine the expression of GNG5 in glioma. Based on clinical data and CGGA database, we identified the correlation between GNG5 and multiple molecular and clinical features and prognosis using various analytical methods. Co-expression analysis and GSEA were performed to detect GNG5-related genes in glioma and possible signaling pathways involved. ESTIMATE, ssGSEA, and TIMER were used to detect the relationship between GNG5 and the immune microenvironment. Functional experiments were performed to explore the function of GNG5 in glioma cells. Results: GNG5 is highly expressed in gliomas, and its expression level is positively correlated with pathological grade, histological type, age, and tumor recurrence and negatively correlated with isocitrate dehydrogenase mutation, 1p/19 co-deletion, and chemotherapy. Moreover, GNG5 as an independent risk factor was negatively correlated with the overall survival time. GSEA revealed the potential signaling pathways involved in GNG5 function in gliomas, including cell adhesion molecules signaling pathway. The ssGSEA, ESTIMATE, and TIMER based analysis indicated a correlation between GNG5 expression and various immune cells in glioma. In vivo and in vitro experiments showed that GNG5 could participate in glioma cell proliferation and migration. Conclusions: Based on the large data platform and the use of different databases to corroborate results obtained using various datasets, as well as in vitro and in vivo experiments, our study reveals for the first time that GNG5, as an oncogene, is overexpressed in gliomas and can inhibit the proliferation and migration of glioma cells and lead to poor prognosis of patients. Thus, GNG5 is a potential novel biomarker for the clinical diagnosis and treatment of gliomas. [ABSTRACT FROM AUTHOR]

Abstract Background To investigate the expression of Golgi phosphoprotein-3 (GOLPH3) in prostate cancer and determine its prognostic value. Methods Immunohistochemical staining for GOLPH3 was performed on tissue microarrays of 342 prostate patients. The correlation between GOLPH3 expression with its clinicopathologic factors was also analyzed in order to determine its prognostic significance. Results GOLPH3 expression of normal prostate tissues, benign prostate hyperplasia, high-grade prostatic intraepithelial neoplasia, and hormone-dependent prostate cancer (HDPC) did not show any statistically significant difference. In contrast, statistically significant difference was reported in moderate/intense GOLPH3 expression in cases diagnosed with HDPC and castration resistant prostate cancer (CRPC) (P < 0.0005). Moderate /intense expression of GOLPH3 was associated with androgen independence (P = 0.012), higher Gleason score (P = 0.017), bone metastasis (P = 0.024), higher baseline prostate-specific antigen (PSA) (P = 0.038), and higher PSA nadir (P = 0.032). A significantly negative correlation was found between moderate/intense GOLPH3 expression and disease-free survival (DFS) (HR = 0.28, P = 0.012) and overall survival (OS) (HR = 0.42, P = 0.027). Univariated analysis indicated that moderate/intense GOLPH3 expression created a significantly prognostic impact in patients with CRPC. On the other hand, multivariate analysis indicated that GOLPH3 was a significantly independent prognostic factor of DFS (P = 0.027) in all prostate cancer patients. Conclusions In this study, it was discovered that the overexpression of GOLPH3 is associated with the transition of prostate cancer from hormone sensitive phase to hormone refractory phase. GOLPH3 might be an important prognostic factor of DFS and OS in patients with prostate cancer. In totality, GOLPH3 could be used as a novel candidate in devising a more effective therapeutic strategy to tackle CRPC. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1452541171722856.

aimed to explore the short- and long-term efficacy of surgery for early-stage NPC. Methods: We retrospectively evaluated 341 patients diagnosed with early-stage NPC between September 2010 and December 2015. Among them, 58 patients underwent endoscopic nasopharyngectomy combined with chemoradiotherapy, whereas 283 patients underwent conventional chemoradiotherapy. The patients who underwent concurrent chemoradiotherapy or radiotherapy alone were matched to patients who underwent surgery in a 1:2 ratio using propensity score matching to analyze the clinical efficacy of each therapeutic modality. The primary endpoint was survival, and the secondary endpoints were tumor regression rate and reduction in Epstein–Barr virus (EBV)-DNA levels. Results: After matching, 156 patients were enrolled (58 patients in the surgery group; 98 patients in the non-surgery group). The baseline data of the matched patients had good inter-group comparability (All P> 0.05). The surgery group had significantly higher 5-year overall survival (98.30% vs. 91.70%), disease-free survival (98.30% vs. 81.40%), and recurrence-free survival (100.00% vs. 90.10%) rates than did the non-surgery group (All P< 0.05). In total, 0 and 14 patients in the surgery and non-surgery groups, respectively, had residual cancer at the end of treatment (P=0.001). All patients in the surgery group tested negative for EBV-DNA, whereas two patients in the non-surgery group tested positive. The incidence of hematologic toxicity during treatment was similar between the two groups (All P> 0.05). Still, the incidence of severe oral mucositis was lower in the surgery group than in the non-surgery group (37.9% vs. 54.08%, P=0.051). Conclusion: Surgery can improve the clearance rate of EB virus and reduce tumor residue. Surgery may be a safe and effective treatment for early NPC. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the clinical characteristics of nasopharyngeal carcinoma (NPC) and a concomitant hepatitis B virus (HBV) infection, as well as the potential effects of HBV infection and antiviral therapy on prognosis. Methods: We conducted a retrospective chart review of all NPC patients from December 2010 to December 2014. After collecting medical records and conducting follow‐ups on patients, a total of 876 eligible NPC patients were included. For each patient, medical records were reviewed. Factors predictive of outcome were compared using the log‐rank test and Cox regression analysis. Results: Among the 876 participants, 106 (12.1%) patients were HBV‐infected patients. The hepatitis B surface antigen‐positive [HBsAg(+)] group had a lower CD4+ T cell count than the HBsAg(−) group (P =.048). Among patients with stage I/II NPC, 5‐year overall survival (OS), disease‐free survival (DFS), relapse‐free survival, and distant metastasis‐free survival (DMFS) of the HBsAg(+) group were 82.5%, 70.7%, 87.7%, and 76.6%, respectively, whereas those of the HBsAg(−) group were 91.4%, 86.0%, 93.8%, and 92.1%, respectively. Statistically significant differences in OS, DFS, and DMFS existed between both groups (P =.017,.018, and.004, respectively). The multivariate analysis indicated that HBsAg status and N stage are independent risk factors affecting OS, DFS, and DMFS of NPC patients. A statistically significant difference in 5‐year DMFS existed between the antivirus (90.0%) and no‐antivirus groups (70.0%) (P =.043). Conclusions: Hepatitis B virus infection is an independent risk factor for early stage NPC, which may be associated with its reduced immune functions compared to the HBsAg(−) group. Anti‐HBV treatment may improve the prognosis of HBV‐infected NPC patients. [ABSTRACT FROM AUTHOR]

Introduction: The solute carrier family 12 member 5 (SLC12A5) gene is playing a putative oncogenic role in colorectal carcinoma. However, the status of SLC12A5 amplification and expression in ovarian carcinoma and its potential clinical and/or prognostic significance has not yet been investigated. Methods: In the present study, semi-quantitative staining and fluorescence in situ hybridization were used to investigate SLC12A5 protein expression and gene amplification levels. Samples were obtained from archival, formalin-fixed, paraffin-embedded pathological specimens consisting of 30 normal ovaries, 30 ovarian cystadenomas, 30 borderline ovarian tumors, and 147 invasive ovarian carcinomas. SLC12A5 immunohistochemical staining results, pathological parameters, and patient prognosis were then evaluated using various statistical models. Patient survival rate was also assessed using receiver-operator curve analysis. Results: Our results revealed no SLC12A5 protein overexpression in normal ovaries. However, 7% of cystadenomas had SLC12A5 protein overexpression along with 17% of borderline tumors and 37% of ovarian carcinomas (P<0.01). Amplification of SLC12A5 was detected in 10.3% of ovarian carcinomas. Further correlational analyses showed that SLC12A5 protein overexpression in ovarian carcinomas was significantly associated with ascending histological grade, pT/pN/pM status, as well as FIGO stage (P<0.05). A subsequent univariate survival analysis of our ovarian carcinoma cohorts resulted in a significant association between SLC12A5 protein overexpression and decreased patient survival (44.3 and 85.9 months for high and low SLC12A5 protein expression, respectively; P<0.001). Importantly, additional multivariate analysis revealed that SLC12A5 protein expression was a significant, independent prognostic factor for overall survival in ovarian carcinoma patients (P=0.003). Conclusions: Collectively, these findings support the conclusion that SLC12A5 protein overexpression could indicate an invasive and/or aggressive phenotype of ovarian carcinoma. Future work will need to investigate whether SLC12A5 protein can serve as an independent prognostic molecular marker in patients with ovarian carcinoma. [ABSTRACT FROM AUTHOR]

Objective: Two distinct forms of FMS-like tyrosine kinase 3 (FLT3) mutations, internal tandem duplication (ITD) in the juxtamembrane domain and point mutation within the activation loop of the tyrosine kinase domain (TKD), have been identified in considerable number of patients with AML. This study was aimed to analyze the impacts of these mutations on clinical outcomes, and assess the efficacy of different therapeutic regimens (allo-HSCT, sorafenib, or conventional chemotherapy) for AML patients with FLT3 mutations after the standard induction therapy. Materials and methods: We analyzed DNA samples from 158 consecutive de novo AML patients (18-60 years, excluding APL) with FLT3 mutations between July 2010 and October 2015. Results: We found that AML patients with FLT3-TKD mutations have more favorable clinical outcomes than those with FLT3-ITD mutations. We also found that allo-HSCT therapy subgroup achieved longer OS and RFS than non-allo-HSCT therapy subgroup for FLT3-ITD positive patients (p < 0.001, p = 0.071). However, compared with the clinical outcomes in nonprimary refractory patients, sorafenib did not show an obvious beneficial effect for the primary refractory patients. Further study on a large scale is still recommended. Conclusions: FLT3-TKD-mutated AML patients have more favorable clinical outcomes than those with FLT3-ITD mutations. Allo-HSCT therapy subgroup achieved longer OS and RFS than non-allo-HSCT therapy subgroup for FLT3-ITD positive patients. Compared with the clinical outcomes in non-primary refractory patients, sorafenib did not show an obvious beneficial effect for the primary refractory patients. [ABSTRACT FROM AUTHOR]

Loss of CRY2 confers aggressive phenotypes to breast cancer. However, the mechanism of its downregulation and its prognostic value in breast cancer are still not clear. Our data mining in TCGA breast cancer cohort (TCGA-BRCA) showed that the luminal A subtype of breast cancer had the highest CRY2 expression, while the basal-like subtype had the lowest CRY2 expression. The ER+ group had significantly higher CRY2 expression than the ER- group. Demethylation treatment using 5-AZA-dC significantly restored CRY2 expression in MDA-MB-231 and BT549 cells. Co-expression analysis in TCGA-BRCA showed a strong negative correlation between CRY2 and FOXM1 (Pearson's r = −0.62). FOXM1 overexpression in MCF-7 cells reduced CRY2 expression, while FOXM1 knockdown in MDA-MB-231 cells increased CRY2 expression. Demethylation significantly abrogated FOXM1 induced CRY2 suppression in MCF-7 cells. Bioinformatic scanning predicted a common FOXM1 binding site in CRY2 transcript 1 and transcript 2 promoter. The following studies confirmed that through binding with DNMT3b, FOXM1 can bind to CRY2 promoter and enhance methylation in this region. Univariate analysis based on Cox proportional hazards model and the following NPI and AOL adjusted studies in bc-GenExMiner 4.0 showed that high CRY2 expression was an independent indicator of reduced risk of metastatic relapse (MR) in ER+ breast cancer patients, but not in ER- breast cancer. With these findings, we infer that FOXM1 is a negative regulator of CRY2 in breast cancer via enhancing methylation in CRY2 promoter and its high expression is an independent predictor of favorable MR-free survival in ER+ breast cancer patients. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to report the outcomes of patients undergoing vesicovaginal fistula (VVF) repair to identify prognostic factors. Materials and Methods: Patients who underwent VVF repair between January 2009 and October 2015 were reviewed. Primary outcome was fistula closure at 3 months. Results: A total of 123 patients and 139 procedures of VVF repair were reviewed. The overall success rate was 85.6%. There were no significant differences in age (p = 0.476), etiology (p = 0.900), fistula duration (p = 0.491) and number of repairs (p = 0.509) between success and fail group. Moderate or severe perifistula fibrosis and multiple fistula were associated with failure in repair of fistula (70.8 vs. 93.4%, p < 0.001; 62.5 vs. 88.6%, p = 0.005). No difference was seen in success rate of vaginal and abdominal approaches (86.0 vs. 85.0%, p = 0.800). Logistic regression analysis identified fistula number (p = 0.003) and perifistula fibrosis (p = 0.002) as 2 independent prognostic factors. Medium/large fistulas were 3.2 times more likely to fail in repair than small fistulas (OR 3.2, 95% CI 0.95-10.6, p = 0.061). Conclusions: Fistula number and perifistula fibrosis were 2 independent prognostic factors for fistula repair. Unsuccessful closure was more likely in medium/large VVF. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinicopathologic features, diagonsis and prognosis of testicular borderline mucinous tumor. Methods One case of testicular borderline mucinous tumor tissue was prepared for EnVision two-step immunohistochemical staining, and the pertinent literature was reviewed. Results The right testis grew gradually with occasional pain. Histologically, the boundary of the tumor tissues was clear, the capsule was complete, the tumor was consisted of multiple cavities, the cavities were lined by intestinal-type epithelium, some were single-layer columnar epithelium, some were papillary proliferation and pseudostratification with mild-moderate nuclear atypia were present. There was no solid cell nests, stromal invasion or pathologic mitosis. Immunophenotype: PCK, CEA, CA19-9 were positive in tumor epithelium, the scattered neuroendocrine cells stained with CgA, Actin was positive in the smooth muscle around the tumor epithelium. Ki-67 showed 45% of labeled nuclei of tumor cells. VIMENTIN, PSMA, PLAP, AFP, Calretinin, MC, Syn were carried out with negative results. Conclusions The primary testicular mucinous tumor is rare, but as for the existing data, this type of testicular tumor resembles the ovarian counterparts, exhibits the same morphologic spectrum, classification, and the prognosis is probably the same. It is very important for the differential diagnosis to closely link the clinical characteristics and imageological detection. [ABSTRACT FROM AUTHOR]

Sex-determining region Y-related high mobility group box 4 (SOX4) has been proven to serve as a critical role in cancer development and progression. However, little is known about the pathological role of SOX4 in breast cancer patients. The purpose of this study is to measure the expression of SOX4 in breast cancer patients and to explore the clinical significance of SOX4. Using RT-PCR and Western blot, messenger RNA (mRNA) and protein expression of SOX4 were measured in breast cancer tissues and adjacent normal mammary tissues. The relationship of SOX4 expression with clinical characteristics of 148 breast cancer patients was analyzed by immunohistochemistry. In the present study, our results indicated that SOX4 mRNA and protein were highly expressed in breast cancer tissues compared with adjacent normal mammary tissues and positively correlated with clinical stage (I-II vs. III-IV; P = 0.008), T classification (T1-T2 vs. T3-T4; P = 0.013), N classification (N0-N1 vs. N2-N3; P < 0.001), M classification (M0 vs. M1; P = 0.001), estrogen receptor (negative vs. positive; P = 0.029), progesterone receptor (negative vs. positive; P = 0.004), and histological grade (G1 vs. G2-G3; P = 0.033) in breast cancer patients. Furthermore, we also found that SOX4 protein overexpression was an unfavorable prognostic factor in breast cancer patients ( P < 0.001), regardless of clinical stage, tumor size, lymph node metastasis, and distant metastasis. Finally, high SOX4 expression was an independent poor prognostic factor for pancreatic patients through multivariate analysis ( P = 0.033). In conclusion, SOX4 overexpression serves as an unfavorable prognostic biomarker in breast cancer patients. [ABSTRACT FROM AUTHOR]

Objective To detect the expression of prostate-specific Membrane Antigen (PSMA), and α-methylacyl CoA Racemase (AMACR) in prostate carcinoma and explore its significance in the development of prostate carcinoma. Method The expression of PSMA, and AMACR was detected by immunohistochemistry. Results (1) The expression levels of PSMA were higher in prostate carcinoma (Pca) than those in benign prostatic hyperplasia (BPH) (P = 0.000) and high grade prostatic intraepithelial neoplasia (HGPIN) (P = 0.005), there was no correlation between Gleason score, prognosisand the expression of PSMA (P > 0.05). 2. The expression levels of AMACR in BPH were obviously lower than those of in HGPIN (P = 0.000) and Pca (P = 0.000), the expression of AMACR was negatively correlated with Gleason score (P = 0.005, rs = -0.430) ; and was not correlated with prognosis (P > 0.05). Conclusion PSMA and AMACR play a role in the development of prostate carcinoma, but could not be as predictors of prognosis. [ABSTRACT FROM AUTHOR]

Abstract: The prognostic value of absolute lymphocyte count (ALC) has been a recent matter of debate in childhood acute lymphoblastic leukemia (ALL). In the current study, ALCs at the time of diagnosis (ALC-0), after 7 days of initial therapy (ALC-8) and at interim of the induction therapy (ALC-22) were examined in Chinese children with B-cell precursor (BCP) ALL and correlated with the level of minimal residual disease (MRD) at day 22 of induction therapy. Medical and laboratory records of 140 patients diagnosed with childhood BCP ALL were retrieved and analyzed. ALC-22 is significantly correlated with MRD level at day 22 of therapy and can be a good prognostic factor for childhood BCP-ALL. Furthermore, lymphocyte count at initial diagnosis is correlated with MRD level at day 22 in childhood BCP-ALL with the immnunophenotype of CD19pos/CD10pos/CD34pos/CD45neg and role as a new prognostic factor was determined. [Copyright &y& Elsevier]

Abstract: Objective: The forkhead box M1 (FOXM1) transcription factor plays crucial roles in regulating the proliferation, differentiation, and transformation of cells. Overexpression of FOXM1 is associated with a variety of aggressive solid carcinomas, including cervical cancer. However, the precise role and molecular mechanism responsible for the aggressive action of FOXM1 in cervical cancer remain unclear. This study investigated the cellular and molecular aggressive function of FOXM1 in cervical cancer. Methods: The FOXM1 gene and protein expression profiles were determined by quantitative polymerase chain reaction, Western blotting and immunohistochemical staining, and other cellular and molecular approaches including gene transfection, short hairpin RNA interference (RNAi), and wound‐healing, migration, and invasion assays. Results: FOXM1 expression was significantly up-regulated at both mRNA and protein levels in early-stage cervical cancer, compared to cervical intraepithelial neoplasia and normal cervical tissues. High levels of FOXM1 expression were significantly associated with aggression in cervical cancer, and were an independent prognostic factor for poor survival in early-stage cervical cancer patients. Moreover, enforced expression of FOXM1 increased migration and invasion of cancer cells, whereas RNAi-mediated knockdown of FOXM1 had the opposite effect. In addition, up-regulation of FOXM1 increased the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 in vitro and in vivo, and activated the Akt/glycogen synthase kinase-3β/Snail pathway, resulting in the promotion of migration and invasion of cervical cancer cells. Conclusions: These results suggest that FOXM1 up-regulation is associated with poor prognosis in early-stage cervical cancer, and therefore it may act as a prognostic marker and a new potential target for cervical cancer treatment. [Copyright &y& Elsevier]

This study aims to investigate the expression and significance of EphA2 and EphrinA-1 in human gastric adenocarcinoma progression and prognosis. The expression of EphA2 and EphrinA-1 was detected in the cell lines and tissues of gastric adenocarcinoma. Different expression levels of EphA2 and EphrinA-1 were found in two cell lines. The expression of EphA2 and EphrinA-1 was significantly higher in gastric adenocarcinoma tissues than in normal tissues. Statistical analysis showed a significant correlation of EphA2 expression with the depth of tumor invasion, tumor-node-metastasis (TNM) stages, and lymph node metastasis. EphrinA-1 over-expression was significantly correlated with TNM stages and lymph node metastasis, while EphA2 expression was found to be an independent prognostic factor of postoperative gastric adenocarcinoma. In conclusion, the increased expression of EphA2 and EphrinA-1 plays an important role in the progression of human gastric adenocarcinoma, in which elevated EphA2 expression is an independent factor that indicates poor prognosis in postoperative gastric adenocarcinoma. [ABSTRACT FROM AUTHOR]

Abstract: Therapeutic hypothermia is a promising treatment for patients with severe traumatic brain injury (TBI). We present here the results of a study in which noninvasive selective brain cooling (SBC) was achieved using a head cap and neckband. Ninety patients with severe TBI were divided into a normothermia control group (n =45) and a SBC group (n =45), whose brain temperature was maintained at 33–35°C for 3 days using a combination of head and neck cooling. At 24, 48 and 72h after injury, the mean intracranial pressure (ICP) values of the patients who underwent SBC were lower than those of the normothermia controls (19.14±2.33, 19.72±1.73 and 17.29±2.07 mmHg, versus 23.41±2.51, 20.97±1.86, and 20.13±1.87 mmHg, respectively, P <0.01). There was a significant difference in the neurological recovery of the two groups at the 6-month follow-up after TBI. Good neurological outcome (Glasgow Outcome Scale score of 4 to 5) rates 6 months after injury were 68.9% for the SBC group, and 46.7% for the control group (P <0.05). There were no complications resulting in severe sequelae. In conclusion, the noninvasive SBC described here is a safe method of administering therapeutic hypothermia, which can reduce ICP and improve prognosis without severe complications in patients with severe TBI. [Copyright &y& Elsevier]

Hyperprogressive disease (HPD) is an unexpected response pattern observed in immune checkpoint therapy and associated with poor prognosis in several cancers. Such patients can't benefit from immunotherapy and even experience a rapid disease progression. At present, many researchers have explored the HPD phenomenon, but there is no consensual definition of HPD in different studies. The incidence of HPD is about 4%-29% in various tumors. Many studies demonstrated that HPD was associated with worse prognosis, but the mechanism of HPD has not yet been fully clarified. Predictive factors in patients with HPD before treatment is one of the keys to managing patients receiving immune checkpoint inhibitors. Some factors, such as MDM2/4 amplification, EGFR mutations, and old age may be risk factors for HPD, but the results are discordant in different studies. Performing imaging evaluation and biopsy as early as possible is the main method to avoid the iatrogenic injury of immunotherapy at present. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is a common malignant tumour type of the digestive system. Long non-coding RNA (lncRNA) c-Myc upregulated (MYU), also known as VPS9 domain-containing 1 antisense 1, was recently discovered. However, the expression of lncRNA MYU in ESCC and its role in tumour progression have remained elusive. In the present study, the expression of lncRNA MYU, Ki-67 and the epithelial-mesenchymal transition-related proteins E-cadherin and Vimentin in ESCC tissues was detected by reverse transcription-quantitative PCR. The expression of Ki-67, E-cadherin and Vimentin in ESCC tissues was also detected by immunohistochemistry. A small interfering RNA plasmid was employed to establish a TE-2 cell line with knockdown on lncRNA MYU. The results indicated that the expression of lncRNA MYU was higher in ESCC tissues than in normal adjacent tissues and that upregulation of lncRNA MYU was a potential biomarker for poor prognosis. The results also suggested that the expression levels of lncRNA MYU were correlated with the histological grade, lymph node metastasis and TNM stage (P<0.05). Silencing of lncRNA MYU expression inhibited the proliferation, migration and invasion, while the expression of lncRNA MYU increased as cell proliferation increased. In addition, the mRNA expression of Vimentin and Ki-67 was decreased in TE-2 cells after lncRNA MYU was knocked down, while E-cadherin mRNA expression was elevated. In conclusion, the present results indicated that lncRNA MYU may regulate the proliferation, migration and invasion of ESCC cells, and may serve as a prognostic biomarker for ESCC. [ABSTRACT FROM AUTHOR]

Abstract: Aim: WD40 repeat-containing 62 (WDR62) is a centrosome-associated gene involved in cell cycling and proliferation. However, the role of WDR62 in human malignancies remains unknown. The present study aimed to identify the role, if any, of WDR62 in the pathogenesis of human gastric cancer (GC). Methods: WDR62 expression in 372 cases of human GC and eight GC cell lines was determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), immunohistochemistry and Western blotting. Correlations between WDR62 expression and clinicopathological characteristics, as well as GC prognosis were determined. WDR62 regulation of GC cell proliferation, invasion, migration and cell cycle distribution were studied both in vitro and in vivo. Results: WDR62 expression was significantly increased in GC tissues and cell lines and was associated with poor differentiation and prognosis of GC. WDR62 expression was elevated in GC multidrug resistant cells. Suppressing WDR62 significantly decreased cell proliferation and induced G2/M phase arrest of GC cells. Consistently, WDR62 knockdown inhibited gastric carcinogenesis in nude mice. Regulation of Akt/p38-mitogen-activated protein kinase (MAPK)/multidrug resistance gene 1 (MDR1) expression and activation by WDR62 contributed to the chemoresistance of GC cells. WDR62 overexpresses in GC and the suppression of WDR62 inhibits GC cell growth by inducing G2/M cell cycle arrest. Conclusion: WDR62 may be a novel prognostic marker and a potential chemotherapy target for GC. [Copyright &y& Elsevier]

Abstract: This study was designed to investigate the association of HAb18G/CD147 expression and localization with clinicopathological parameters and prognosis in NSCLC. Two hundred and eight (208) specimens of surgically resected NSCLC were stained by immunohistochemistry utilizing mouse anti-human HAb18G/CD147 monoclonal antibody. High levels of HAb18G/CD147 expression were associated with male gender, smoking history, tumor position, distant metastasis status, and clinical stage (p <0.05) in squamous cell carcinoma. In adenocarcinomas, HAb18G/CD147 expression was associated with male gender, tumor diameter, differentiation, lymph node status, distant metastasis status, and clinical stage (p <0.05). HAb18G/CD147 expression with higher PU was predominantly localized in the tumor cell membranes rather than in cytoplasms. In squamous cell carcinomas, membranous localization of HAb18G/CD147 was linked to distant metastasis status and TNM stage (p <0.05). Cytoplasmic localization of HAb18G/CD147 was associated with male gender and smoking history. In adenocarcinomas, membranous localization of HAb18G/CD147 correlated with tumor diameter, differentiation and distant metastasis (p <0.05). Univariate analysis indicated that patients with high HAb18G/CD147 expression and membranous localization predicted poor prognosis in both squamous cell carcinomas and adenocarcinomas. Multivariate analysis showed that lymph node status (HR=1.762, 95%CI 1.105–2.811, p =0.017), distant metastasis status (HR=3.789, 95%CI 2.196–6.539, p =0.000), expression (HR=6.632, 95%CI 2.457–17.904, p =0.000), and localization (HR=0.520, 95%CI 0.341–0.794, p =0.002) were good or excellent independent predictors of patient survival. HAb18G/CD147 is a biomarker characterizing progression and survival of NSCLC. More importantly, its cellular localizations should be considered in the analysis of clinicopathological characteristics and prognostic factors in NSCLC. [Copyright &y& Elsevier]

Abstract: Flow cytometry based minimal residual disease (MRD) was evaluated for outcome prediction in childhood acute myeloid leukemia (AML). The median levels of MRD in relapsed and nonrelapsed patients were different after the first induction (0.64% vs. 0.18%, P =0.030). A cutoff level of ≥0.25% after the first course of induction was correlated with a high risk of relapse in both univariate analysis (5-year cumulative incidence of relapse: 66.8% vs. 21.2%, P =0.002) and multivariate analyses (hazard ratio: 3.70, 95% CI, 1.23–11.08, P =0.020). Our results showed that MRD level after the first induction therapy provides important information for risk assessment in childhood AML. [Copyright &y& Elsevier]

Objective: To investigate the contribution of cellular senescence to the progression and prognosis of myelodysplastic syndrome (MDS). Materials and Methods: We have analyzed the expression of p16INK4a in bone marrow mononuclear cells or CD34+ cells from 53 patients with MDS, 12 acute myeloid leukemia (AML), and 11 healthy controls. Additionally, We have assessed quantitatively senescence-associated β-galactosidase (SA-β-gal) staining on bone marrow mononuclear cells from MDS and AML patients, HL60 and SHI-1 leukemia cell lines, and healthy control cells. Results: An upregulated expression of senescence-associated molecular marker p16INK4a was found in MDS compared with healthy controls, while a lower expression of p16INK4a was observed in AML compared with healthy controls. International Prognostic Scoring System score was negatively correlated with the percentage of p16INK4a-positive cells. The SA-β-gal activity measured by mean percentage of positive cells was significantly higher in MDS cases when compared with controls. Meanwhile, percentage of SA-β-gal–positive cells was also remarkably higher in dysplastic cells of MDS when compared to nondysplastic cells from MDS. Conclusions: These results of our present study suggested an accelerated cellular senescence occurred in MDS, and the cellular senescence may be involved in the progression and prognosis of MDS. [Copyright &y& Elsevier]

Background Low bone mass in patients with adolescent idiopathic scoliosis has been well reported. Poor bone quality was regarded as a new and unique prognostic factor in aggravating curve progression. However, the potential biomechanical correlation between them remains unclear. Methods Three-dimensional finite element models of idiopathic scoliotic spine with different bone mineral status were created for axial loading simulation. An axial load of 3 different body weights was applied on different bone mineral mass models. The mechanical responses of the vertebral cortical and cancellous bone, facet joints, end plate, and intervertebral disc were analyzed. Results Accompanied with the low bone mineral status, thoracic scoliosis produced asymmetric and higher stress in the cortical bone, lumbar facet joints, and end plate at the concave side of the thoracic structure curve. Stress increased in the disc at the apex of the scoliosis, whereas it mildly decreased in the L4-5 and L5-S1 disc. Body weight gain increased the stress in scoliotic spine structures in all bone mineral statues. Conclusions Biomechanical simulations indicated that low bone mineral mass might aggravate curve progression and induce more serious lumbar compensatory scoliosis in patients with adolescent idiopathic scoliosis. Weight gain was also a risk factor for curve progression. [ABSTRACT FROM AUTHOR]