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The clinical significance of the combination of neutrophil–lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) is unclear. This study investigated the predictive value of pretreatment NLR (pre-NLR) combined with pretreatment PLR (pre-PLR) for the survival and prognosis of nasopharyngeal carcinoma (NPC). A total of 765 patients with non-metastatic NPC from two hospitals were retrospectively analyzed. The pre-NLR-PLR groups were as follows: HRG, high pre-NLR and high pre-PLR. MRG, high pre-NLR and low pre-PLR or low pre-NLR and high pre-PLR. LRG, neither high pre-NLR nor high pre-PLR. Receiver operating characteristic (ROC) curves were used to identify the cutoff-value and discriminant performance of the model. We compared survival rates and factors affecting the prognosis among different groups. The 5-year overall survival (OS), local regional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) of NPC patients in HRG were significantly poorer than those in MRG and LRG. The pre-NLR-PLR score was positively correlated with T stage, clinical stage, ECOG, and pathological classification. Multivariate cox regression analysis showed that pre-NLR-PLR scoring system, ECOG, pre-ALB, pre-CRP and pre-LMR were independent risk factors affecting 5-year OS, LRRFS and DMFS. The ROC curve showed that area under the curve (AUC) values of pre-NLR-PLR of 5-year OS, LRRFS and DMFS were higher than those of pre-NLR and pre-PLR. pre-NLR-PLR is an independent risk factor for the prognosis of NPC. The pre-NLR-PLR scoring system can be used as an individualized clinical assessment tool to predict the prognosis of patients with non-metastatic NPC more accurately and easily. [ABSTRACT FROM AUTHOR]

Purpose. The purpose of the current study was to analyze the influence of radiological "disappearing liver metastasis" (DLM) on the efficacy and prognosis of patients with colorectal liver metastases (CRLM) undergoing conversion therapy. Methods. Patients with CRLM by the multidisciplinary team (MDT) of the First Affiliated Hospital of Chongqing Medical University were retrospectively enrolled from January 2014 to January 2021. The relationship between the occurrence and recurrence of DLM and different clinical factors was analyzed. Results. Thirty-five of the 113 patients (31.0%) with initially unresectable CRLM developed DLM, and of the 361 lesions, 177 disappeared (49.0%). Within 6 months, 6-12 months, and 12-24 months groups, the recurrence rate was 3.4%, 16.8%, and 34.8%, but there is no recurrence in after 24 months group. There was a statistical difference between chemotherapy alone and chemotherapy combined with the targeted therapy group on the occurrence of DLM (58.3% vs. 37.1%, P < 0.001). There were significant differences between <5 mm group and >10 mm group on occurrence of DLM（76.7% vs. 30.4%, P < 0.001) and between 5-10 mm group and >10 mm group also (70.0% vs. 30.4%, P < 0.001). Through univariate and multivariate analyses, it was concluded that age (P = 0.026 , 95 % CI = 3.690) and treatment regimens (P = 0.033 , 95 % CI = 2.703) had a significant influence on the progression-free survival (PFS) time of DLM. Conclusion. Younger patients, who use chemotherapy alone to achieve a therapeutic effect, might have better survival benefits when the lesions do not progress within 2 years after the appearance of DLMs. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a high mortality disease, the fifth most general cancer worldwide, and the second leading to cancer-related deaths, with more than 500,000 new patients diagnosed each year. First, the high expression of centromere M (CENPM) in mammary gland tissue of b-catenin transformed mice was identified. Materials and methods: In our study, we evaluated the expression of CENPM in hepatocellular carcinoma based on data obtained from an online database. Multivariate analysis showed that the expression of CENPM and M classification was an independent prognostic factor for patients with hepatocellular carcinoma. Results: Survival analysis showed that patients with high CENPM had a worse prognosis than patients with low CENPM (P < 0.01). A multivariate Cox regression hazard model showed that B cells, CD8+ T cells, macrophages, and dendritic cells infiltrated by immune cells were statistically significant in liver cancer (P < 0.05). Using the network, the 50 most frequently changed neighbor genes of CENPM were shown, and the most common change was RAD21 (18.3%). Conclusion: Our study found that the expression of CENPM was significantly increased in patients with hepatocellular carcinoma, and it was related to a variety of clinical characteristics, its correlation with the level of immune infiltration and poor prognosis, so CENPM can be used as a useful prognosis for patients’ markers and HCC. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC), is the fifth most common cancer in the world and the second most common cause of cancer-related deaths. Over 500,000 new HCC cases are diagnosed each year. Combining advanced genomic analysis with proteomic characterization not only has great potential in the discovery of useful biomarkers but also drives the development of new diagnostic methods.Methods: This study obtained proteomic data from Clinical Proteomic Tumor Analysis Consortium (CPTAC) and validated in The Cancer Proteome Atlas (TCPA) and TCGA dataset to identify HCC biomarkers and the dysfunctional of proteogenomics.Results: The CPTAC database contained data for 159 patients diagnosed with Hepatitis-B related HCC and 422 differentially expressed proteins (112 upregulated and 310 downregulated proteins). Restricting our analysis to the intersection in survival-related proteins between CPTAC and TCPA database revealed four coverage survival-related proteins including PCNA, MSH6, CDK1, and ASNS.Conclusion: This study established a novel protein signature for HCC prognosis prediction using data retrieved from online databases. However, the signatures need to be verified using independent cohorts and functional experiments. [ABSTRACT FROM AUTHOR]

High expression and role of tumor necrosis factor receptor 2 (TNFR2) in cancer progression and prognosis has been reported in several types of tumors. However, its role in esophageal carcinoma (EC) remains unknown. In the present study, TNFR2 expression in middle and lower thoracic esophageal squamous cell carcinoma (ESCC) was detected using immunohistochemistry (IHC). Chi‑square test revealed that TNFR2 was positively correlated with invasion depth, advanced clinical stage and low differentiation degree. Furthermore, survival analysis revealed that TNFR2 was positively correlated with poor overall survival (OS). Moreover, univariate COX regression analysis revealed that clinical stage, lymph node involvement, and invasion depth can affect the OS of ESCC patients, while multivariate COX regression analysis revealed that lymph node involvement and invasion depth can affect the OS of ESCC patients. In middle thoracic ESCC patients, TNFR2 was positively correlated with invasion depth, advanced clinical stage and poor OS. Furthermore, univariate and multivariate COX regression analysis both revealed that clinical stage, lymph node involvement, and invasion depth can affect OS. In lower thoracic ESCC patients, TNFR2 was positively correlated with low differentiation degree. Furthermore, the positive correlation of TNFR2 with poor OS did not reach statistical significance. In addition, univariate COX regression analysis revealed that only lymph node involvement could affect OS. All the results suggest that TNFR2 can play an important role in the progression and poor prognosis of ESCC patients. Moreover, the role of TNFR2 in the prognosis of middle thoracic ESCC patients was earlier and stronger than in lower thoracic ESCC patients. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the expression and prognostic value of microRNA-135a (miR-135a) and matrix metalloproteinase-13 (MMP-13) in serum of colon cancer (CC). A total of 117 cases of patients admitted to Sheng Li Oil Field Central Hospital from May 2015 to May 2017 were enrolled in the research group (RG), and 120 cases of subjects undergoing normal health examination were included in the control group (CG). The expression of miR-135 and MMP-13 in peripheral blood of the two groups were compared, and their values were analyzed. It was found that miR-135a was decreased and MMP-13 was increased in the RG (P<0.050), both of which were closely related to the pathological features and prognosis of CC (P<0.050), and was also significantly correlated with CEA (P<0.001). ROC curve analysis showed that both of them had great predictive value for the occurrence, prognosis and death of CC. In conclusion, miR-135a was low expressed in CC, while MMP-13 was increased in CC, suggesting that the combined detection of the two had a good diagnostic effect on the occurrence of CC, and was closely related to the prognosis of CCC patients, which might be an excellent potential indicator for the diagnosis and treatment of CC in the future. [ABSTRACT FROM AUTHOR]

Somatostatin analogues have recently been used as therapeutic targets for metastatic or surgically unresectable gastroenteropancreatic (GEP) neuroendocrine tumors (NETs), and associated somatostatin receptor (SSTR) expression has been well demonstrated in most GEP NETs, with the exception of rectal NETs. SSTR2 immunohistochemical expressions were evaluated in 350 surgically or endoscopically resected rectal NETs and compared to clinicopathologic factors. SSTR2 expression was observed in 234 (66.9%) rectal NET cases and associated tumors with smaller size (p = 0.001), low pT classification (p = 0.030), low AJCC tumor stage (p = 0.012), and absence of chromogranin expression (p = 0.009). Patients with rectal NET and SSTR2 expression had significantly better overall survival than those without SSTR2 expression both by univariable (p = 0.006) and multivariable (p = 0.014) analyses. In summary, approximately two-thirds of rectal NETs expressed SSTR2. SSTR2 expression was significantly associated with favorable behavior and good overall survival in patients with rectal NETs. Furthermore, SSTR2 expression can be used as prognostic factors. When metastatic disease occurs, SSTR2 expression can be used a possible target for somatostatin analogues. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC), one of the most common malignant tumors worldwide, ranks as the fifth most common cancer and has been the second most frequent cause of cancer-related death. RNA binding proteins (RBPs) are proteins that interact with different classes of RNA and are commonly detected in cells.Methods: We used RNA sequencing data from TCGA to display dysfunctional RBPs microenvironments and provide potential useful biomarkers for HCC diagnosis and prognosis.Results: 330 differently expressed RBPs (208 upregulated and 122 downregulated) were identified. KEGG were mainly enriched in RNA degradation, Influenza A, Hepatitis C, RIG-I-like receptor signaling pathway, Herpes simplex virus 1 infection and RNA transport. CBioPortal results demonstrated that these genes were altered in 50 samples out of 357 HCC patients (14%) and the amplification of BRCA1 was the largest frequent copy-number alteration.Conclusion: Based on the online database, we identified novel RBPs markers for the prognosis of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Papillary and non-papillary are two histological patterns of bladder carcinogenesis and are considered as dual-track oncogenic pathways, which have different genetic alterations. The TCGA-bladder cancer (BLCA) database contains clinicopathological, genomic and survival data from over 400 muscle-invasive bladder cancer patients. In this study, using data from this database, we performed a systematic screening of gene expression to identify the protein-coding gene that might have prognostic value in papillary and non-papillary muscle-invasive bladder cancer (MIBC). The data of patients with primary MIBC in TCGA-BLCA was acquired from the UCSC Xena project (http://xena.ucsc.edu) for re-analysis. By setting |log2 fold change|≥2 and adjusted p value <0.01 as the screening criteria, we found 751 significantly dysregulated genes, including 183 overexpressed and 568 downregulated genes. HMMR was identified as a potential prognostic marker with unique expression. Multivariate analysis showed that its expression was an independent prognostic indicator of shorter progression-free survival (PFS) (HR: 1.400, 95%CI: 1.021–1.920, p = 0.037) in the papillary subtype. ENST00000393915.8 and ENST00000358715.3, two transcripts that contain all 18 exons and encode the full length of HMMR , were significantly upregulated in cancer tissues compared with normal bladder tissues. None of the 17 CpG sites in its DNA locus was relevant to HMMR expression. 26/403 (6.5%) MIBC cases had HMMR gene-level amplification, which was associated with upregulated HMMR expression compared with the copy-neutral and deletion groups. Gene set enrichment analysis (GSEA) in papillary MIBC found that the high HMMR expression group was associated with upregulated genes enriched in multiple gene sets with well-established role in BC development, including G2M checkpoint, E2 F Targets, Myc Targets V1, Myc Targets V2 and Glycolysis. Based on these findings, we infer that HMMR expression might be a specific prognostic marker in terms of PFS in papillary MIBC. DNA amplification might be an important mechanism of its elevation. [ABSTRACT FROM AUTHOR]

Background: Primary cardiac sarcomas are rare and their clinicopathologic features are heterogeneous. Among them, particularly intimal sarcoma is a diagnostic challenge due to nonspecific histologic features. Recently, MDM2 amplification reported to be a characteristic genetic event in the intimal sarcoma. In this study, we aimed to identify the types and incidence of primary cardiac sarcomas that occurred over 25 years in tertiary medical institutions, and to find clinicopatholgical significance through reclassification of diagnoses using additional immunohistochemistry (IHC). Methods: We reviewed the primary cardiac sarcoma cases between January 1993 and June 2018 at Asan Medical Center, South Korea, with their clinicopathologic findings, and reclassified the subtypes, especially using IHC for MDM2 and then, analyzed the significance of prognosis. Results: Forty‐eight (6.8%) cases of a primary cardiac sarcoma were retrieved. The tumors most frequently involved the right atrium (n = 25, 52.1%), and the most frequent tumor subtype was angiosarcoma (n = 23, 47.9%). Seven cases (53.8%) were newly reclassified as an intimal sarcoma by IHC for MDM2. Twenty‐nine (60.4%) patients died of disease (mean, 19.8 months). Four patients underwent a heart transplantation and had a median survival of 26.8 months. This transplantation group tended to show good clinical outcomes in the earlier stages, but this was not statistically significant (p = 0.318). MDM2 positive intimal sarcoma showed the better overall survival (p = 0.003) than undifferentiated pleomorphic sarcoma. Adjuvant treatment is beneficial for patient survival (p < 0.001), particularly in angiosarcoma (p < 0.001), but not in intimal sarcoma (p = 0.154). Conclusion: Our study supports the use of adjuvant treatment in primary cardiac sarcoma, as it was associated with a significantly better overall survival rate. Further consideration of tumor histology may be important in determining the optimal use of adjuvant treatment for different types of sarcomas. Therefore, accurate diagnosis by MDM2 test is important condsidering patient's prognosis and treatment. [ABSTRACT FROM AUTHOR]

The transcriptional coactivator tafazzin (TAZ) serves pivotal roles in organ development, tumor initiation and tumor progression. However, to the best of our knowledge, the expression of TAZ and its clinical significance in human medulloblastoma have not been defined. The present study aimed to clarify the clinical and biological significance of TAZ expression in human medulloblastoma. Immunohistochemical staining for TAZ was performed with 72 medulloblastoma and three normal brain tissue samples. A high expression level of TAZ was detected in 65.28% of medulloblastoma tissues, whereas low expression was identified in the normal brain tissues. TAZ expression was significantly associated with medulloblastoma recurrence. However, the expression of TAZ was not associated with sex, age, tumor location, tumor maximal diameter and tumor histology. Furthermore, both the overall survival and tumor-free survival rate of patients with high levels of expression of TAZ were shorter compared with those of patients with tumors expressing low levels of TAZ. In univariate and multivariate Cox regression analyses, TAZ expression was identified as a significant prognostic factor for patients with medulloblastoma. Functionally, downregulation of TAZ inhibited the proliferation and tumor formation of medulloblastoma cells and the expression of cell-cycle associated proteins in Daoy cells. In conclusion, high expression of TAZ may serve as a prognostic marker for patients with medulloblastoma and TAZ may be a potential target for medulloblastoma therapy. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) play critical roles in the progression of laryngeal cancer (LC). In this study, we aimed to investigate whether miR-149 is associated with the prognosis of patients with LC. A total of 97 laryngeal squamous cell carcinoma patients who underwent tumor resection were included in our follow-up study. In vitro studies was performed in cancer cell line Hep-2 to explore the antitumor role of miR-149 in LC. We found that the expression of miR-149 was significantly lower in tumor tissues, compared with vocal cord polyp tissues (P<0.05). Kaplan-Meier analysis revealed that miR-149 expression status is significantly associated with survival duration (log rank test, P<0.05), and multivariate Cox regression analysis revealed that patients with low miR-149 expression had shorter survival times compared with patients with high miR-149 expression. In vitro studies revealed that the exogenous expression of miRNA-149 inhibits the proliferation of human Hep-2 cells and induces cell apoptosis. Our study suggests that miR-149 expression in laryngeal squamous cell carcinoma tissues is critically associated with the prognosis of patients, and the ectopic expression of miR-149 in Hep-2 cells inhibits proliferation and cell cycle progression. [ABSTRACT FROM AUTHOR]

Background. Epithelial ovarian cancer (EOC) is an extremely lethal gynecological malignancy and has the potential to benefit from the immune checkpoint blockade (ICB) therapy, whose efficacy highly depends on the complex tumor microenvironment (TME). Method and Result. We comprehensively analyze the landscape of TME and its prognostic value through immune infiltration analysis, somatic mutation analysis, and survival analysis. The results showed that high infiltration of immune cells predicts favorable clinical outcomes in EOC. Then, the detailed TME landscape of the EOC had been investigated through "xCell" algorithm, Gene set variation analysis (GSVA), cytokines expression analysis, and correlation analysis. It is observed that EOC patients with high infiltrating immune cells have an antitumor phenotype and are highly correlated with immune checkpoints. We further found that dendritic cells (DCs) may play a dominant role in promoting the infiltration of immune cells into TME and forming an antitumor immune phenotype. Finally, we conducted machine-learning Lasso regression, support vector machines (SVMs), and random forest, identifying six DC-related prognostic genes (CXCL9, VSIG4, ALOX5AP, TGFBI, UBD, and CXCL11). And DC-related risk stratify model had been well established and validated. Conclusion. High infiltration of immune cells predicted a better outcome and an antitumor phenotype in EOC, and the DCs might play a dominant role in the initiation of antitumor immune cells. The well-established risk model can be used for prognostic prediction in EOC. [ABSTRACT FROM AUTHOR]

We developed and assessed whether a novel neutrophil-to-hemoglobin and lymphocyte (NHL) score would improve the ability to predict clinical outcome compared with neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) in acute myocardial infarction (AMI). We examined 13,072 AMI patients from the Korean AMI Registry–National Institute of Health database. NHL score was calculated as follows: NHL score (U) = N/(Hb × L), where N, Hb, and L are baseline blood neutrophil, hemoglobin, and lymphocyte count. The primary outcome was the occurrence of major adverse cerebrocardiovascular events (MACCEs) at 2 years. The NLR, SII, and NHL score were independent predictors of 2-year MACCEs. The area under the curve of the NHL score (0.637) for predicting 2-year MACCEs was significantly higher compared with those of SII (0.589) and NLR (0.607). The NHL score significantly improved the reclassification and integrated discrimination compared with NLR (p < 0.0001) and SII (p < 0.0001). A high NHL score (≥ 0.35 U) was an independent predictor of 2-year MACCEs (adjusted hazard ratio, 1.41; 95% confidence interval, 1.29–1.55; p < 0.001). The NHL score could be a novel model for predicting long-term MACCEs in patients with AMI. [ABSTRACT FROM AUTHOR]

Background: Numerous reports on microRNAs have illustrated their role in tumor growth and metastasis. Recently, a new prognostic factor, miR‐125b‐2‐3p, has been identified for predicting chemotherapeutic sensitivity in advanced colorectal cancer (CRC). However, the specific mechanisms and biological functions of miR‐125b‐2‐3p in advanced CRC under chemotherapy have yet to be elucidated. Methods: MiR‐125b‐2‐3p expression was detected by real‐time PCR (RT‐PCR) in CRC tissues. The effects of miR‐125b‐2‐3p on the growth, metastasis, and drug sensitivity of CRC cells were tested in vitro and in vivo. Based on multiple databases, the upstream competitive endogenous RNAs (ceRNAs) and the downstream genes for miR‐125b‐2‐3p were predicted by bioinformatic analysis, followed by the experiments including luciferase reporter assays, western blot assays, and so on. Results: MiR‐125b‐2‐3p was significantly lowly expressed in the tissues and cell lines of CRC. Higher expression of miR‐125b‐2‐3p was associated with relatively lower proliferation rates and fewer metastases. Moreover, overexpressed miR‐125b‐2‐3p remarkably improved chemotherapeutic sensitivity of CRC in vivo and in vitro. Mechanistically, miR‐125b‐2‐3p was absorbed by long noncoding RNA (lncRNA) XIST regulating WEE1 G2 checkpoint kinase (WEE1) expression. The upregulation of miR‐125b‐2‐3p inhibited the proliferation and epithelial‐mesenchymal transition (EMT) of CRC induced by lncRNA XIST. Conclusions: Lower miR‐125b‐2‐3p expression resulted in lower sensitivity of CRC to chemotherapy and was correlated with poorer survival of CRC patients. LncRNA XIST promoted CRC metastasis acting as a ceRNA for miR‐125b‐2‐3p to mediate WEE1 expression. LncRNA XIST‐miR‐125b‐2‐3p‐WEE1 axis not only regulated CRC growth and metastasis but also contributed to chemotherapeutic resistance to CRC. [ABSTRACT FROM AUTHOR]

We developed and assessed whether a novel neutrophil-to-hemoglobin and lymphocyte (NHL) score would improve the ability to predict clinical outcome compared with neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) in acute myocardial infarction (AMI). We examined 13,072 AMI patients from the Korean AMI Registry–National Institute of Health database. NHL score was calculated as follows: NHL score (U) = N/(Hb × L), where N, Hb, and L are baseline blood neutrophil, hemoglobin, and lymphocyte count. The primary outcome was the occurrence of major adverse cerebrocardiovascular events (MACCEs) at 2 years. The NLR, SII, and NHL score were independent predictors of 2-year MACCEs. The area under the curve of the NHL score (0.637) for predicting 2-year MACCEs was significantly higher compared with those of SII (0.589) and NLR (0.607). The NHL score significantly improved the reclassification and integrated discrimination compared with NLR (p < 0.0001) and SII (p < 0.0001). A high NHL score (≥ 0.35 U) was an independent predictor of 2-year MACCEs (adjusted hazard ratio, 1.41; 95% confidence interval, 1.29–1.55; p < 0.001). The NHL score could be a novel model for predicting long-term MACCEs in patients with AMI. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) accounts for high mortality. RNA methylation has recently gained interest as markers in specific tumors. This study aimed to uncover the function of the roles of 25 RNA methylation regulators in GC. Methods: RNA sequence and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. "STRING" and R were performed to analyze the correlation among the methylase. COX and LASSO were performed to screen for prognostic associated RNA methylation regulators. A prognostic model was established based on the expression of methylase. RT-PCR and immunohistochemistry detected the expression of methylase in GC cells and tissue. Kaplan–Meier curve and Cox analysis were applied to evaluate the effectiveness of the model. Results: The prediction model was established based on the expression of m6A RNA methylation regulators FTO (fat mass and obesity-associated) and RBM15 (RNA binding motif protein 15). Based on the model, GC patients were divided into "high risk" and "low risk" groups to compare the differences in survival. The model was re-evaluated with the clinical data of our center. Conclusion: The two-methylase combination model was an independent prognostic factor of GC. [ABSTRACT FROM AUTHOR]

Background: To investigate the clinical significance of ubiquitin-specific peptidase 19 (USP19) expression in gastric cancer (GC) compared with that in normal tissues and gastric cell lines. Methods: USP19 protein expression was analyzed in 212 paired GC samples using immunohistochemical staining. Quantitative real-time PCR (qRT-PCR) and Western blotting were used to detect the level of USP19 in gastric cell lines. The biological functions of USP19 were investigated by MTT assay, colony-forming assay, wound healing assay and gelatin zymography, and apoptotic cells were detected by immunohistochemistry assays in SGC7901 xenograft models. Results: USP19 expression was significantly increased in GC cells and tissues, and the high level of USP19 expression was positively correlated with the Lauren's classification and poor prognosis. Moreover, USP19 was identified as a novel independent prognostic biomarker in GC patients. Enhanced USP19 expression promoted GC cell proliferation and metastasis through reduced cleaved caspase-3 and increased MMP2/MMP9 expression and promoted enzyme activity in the study, and verified the results through The Cancer Genome Atlas (TCGA) and bioinformatic websites from the Kaplan–Meier plotter (http://kmplot.com) and GEPIA (http://gepia2.cancer-pku.cn.). Conclusion: Our study suggests that USP19 promoted tumor progression by inducing MMP2/MMP9 expression and related enzyme activity. Hence, USP19 may be a valuable prognostic predictor for GC, and the USP19-MMP2/MMP9 axis could serve as a therapeutic target. [ABSTRACT FROM AUTHOR]

Intestinal inflammation and mucosal damage in Crohn’s disease (CD) are believed to progress even during clinical remission. We investigated the long-term prognosis of CD patients in clinical remission according to serum C-reactive protein (CRP) levels. This study included 339 CD patients in clinical remission (Crohn’s disease activity index < 150) for more than 6 months between January 2008 and December 2010. Clinical outcomes were compared between patients with normal and elevated CRP levels during clinical remission. During clinical remission, 150 patients had normal CRP consistently and 189 had elevated CRP at least once. During follow-up (median, 7.9 years [interquartile range, 6.8–8.0]), the Kaplan–Meier analysis with the log-rank test showed that normal CRP group had a longer CD-related hospitalization-free survival (P = 0.007) and a longer CD-related intestinal resection-free survival (P = 0.046) than elevated CRP group. In multivariate analysis, elevated CRP was significantly and independently associated with an increased risk of subsequent CD-related hospitalization (adjusted hazard ratio [aHR] 1.787, 95% confidence interval [CI]: 1.245–2.565, P = 0.002) and of subsequent CD-related intestinal resection (aHR 1.726, 95% CI: 1.003–2.969, P = 0.049). The most common reason for CD-related hospitalization was penetrating complications (35.6%). Even when CD patients are in clinical remission, elevated CRP is significantly associated with subsequent CD-related hospitalization and CD-related intestinal resection during follow-up. CD patients in clinical remission but elevated CRP should receive more careful attention and timely interventions to improve long-term outcomes. [ABSTRACT FROM AUTHOR]

Although early treatment of Crohn’s disease (CD) patients with anti-tumor necrosis factor (TNF) agents or immunomodulators (IMs) may improve long-term outcomes, especially those with poor prognostic factors, their effectiveness in Asians remains unclear. In this study, Korean patients with CD naïve to both intestinal surgery and intestinal complications, and with at least two risk factors for progression (diagnosis at age <40 years, systemic corticosteroid treatment <3 months after diagnosis, and perianal fistula at diagnosis) were retrospectively analyzed. Patients were classified into those who started anti-TNFs, or IMs but not anti-TNFs, within 2 years of diagnosis, and those who started anti-TNFs and/or IMs later. Their probabilities of intestinal surgery and intestinal complications were compared. A total of 670 patients were enrolled, 79 in the early anti-TNF, 286 in the early IM, and 305 in the late treatment group. Kaplan-Meier analysis with the log-rank test showed that from starting anti-TNFs/IMs, times to intestinal surgery (P < 0.001), stricturing complications (P = 0.002), and penetrating complications (P < 0.001) were significantly longer in the early anti-TNF/IM groups than in the late treatment group. Multivariate Cox regression analysis showed that, from starting anti-TNFs/IMs, late anti-TNF/IM treatment was independently associated with higher risks of intestinal surgery (adjusted hazard ratio [aHR] 2.321, 95% confidence interval [CI] 1.503–3.584, P < 0.001), behavioral progression (aHR 2.001, 95% CI 1.449–2.763, P < 0.001), stricturing complications (aHR 1.736, 95% CI 1.209–2.493, P = 0.003), and penetrating complications (aHR 3.315, 95% CI 2.094–5.249, P < 0.001) than early treatment. In conclusion, treatment of Asian CD patients having poor prognostic factors with anti-TNFs/IMs within 2 years of diagnosis is associated with better clinical outcomes than later treatment. [ABSTRACT FROM AUTHOR]

Background: Luminal subtype breast cancer accounts for a predominant number of breast cancers. Considering the heterogeneity of the disease, it is urgent to develop novel biomarkers to improve risk stratification and optimize therapy choices. Long non-coding RNA (lncRNA) represents an emerging and understudied class of transcripts that play a significant role in cancer biology. Growing knowledge of cancer-associated lncRNAs contributes to the development of molecular markers for prognosis evaluation and gene therapy. Materials and methods: Three pairs of primary luminal subtype breast cancer tissues and adjacent non-cancerous tissues were collected and sequenced. EBseq algorithm was used to identify differentially expressed lncRNAs. RNA sequencing data from The Cancer Genome Atlas (TCGA) database were used to validate the robustness of our RNA-seq results. Kaplan-Meier and Cox regression analyses were utilized to assess the association between the lncRNAs and overall survival of patients in TCGA cohort. Results: A total of 796 lncRNAs were significantly dysregulated in luminal subtype breast cancer, including 436 upregulated and 360 downregulated lncRNAs. Among them, FAM83H antisense RNA 1 (FAM83H-AS1) was the most upregulated lncRNA, whereas GSN antisense RNA 1 (GSN-AS1) was the most downregulated lncRNA. Moreover, we proved that the high expression level of FAM83H-AS1 indicated unfavorable prognosis not only in luminal subtype breast cancer but also in all subtype breast cancers. To the best of our knowledge, this is the first report indicating that FAM83H-AS1 was involved in luminal subtype breast cancer and was an independent prognostic indicator. Conclusion: Our study provides a rich resource to the research community for further identifying lncRNAs with diagnostic and therapeutic potentials and exploring biological function of lncRNAs in luminal subtype breast cancer. [ABSTRACT FROM AUTHOR]

Aims To explore the expression, methylation pattern, the prognostic value, and the biological consequences of CAMKK2 in gliomas. Methods The expression and methylation pattern of CAMKK2 was inferred and validated from mRNA expression profile (N = 866) and methylation profile (N = 426) of glioma tissue samples, and independent samples were used for further validation by IHC and pyrosequencing. To explore the function of CAMKK2 in gliomas, in vitro studies, colony formation assays and migration and invasion assays were performed. Results We found the upregulation of CAMKK2 in high-grade glioma samples was associated with promoter hypomethylation. An elevated expression of CAMKK2 was associated with worse prognosis. By in vitro assays, we demonstrated that CAMKK2 could promote cell migration, invasion, and proliferation. Conclusions The expression level of CAMKK2 could be regulated by promoter methylation. CAMKK2 serves as a prognostic marker in gliomas and could be a potential therapeutic target in gliomas. [ABSTRACT FROM AUTHOR]

Background: Hexokinase-2 (HK2) and Beta2-adrenergic receptor (Beta2AR) are overexpressed in hepatocellular carcinoma (HCC) tissues and associated with poor prognosis. However, the synergistic effect of HK2 and Beta2AR in HCC prognosis is not elucidated. The present study aims to investigate the association between HK2 and Beta2AR expressions in HCC tissues, and to evaluate the synergistic effect of HK2 and Beta2AR in HCC prognosis.Methods: Immunohistochemistry of HK2 and Beta2AR was performed on 155 paraffin embedded HCC samples retrieved from the archives of pathology department. Corresponding clinical data and prognostic data were collected through searching medical record systems, death registration systems and interviews with patient families. Spearman correlation test was performed to evaluate the association between HK2 and Beta2AR expression. Kaplan-Meier survival curves and Cox regressions were employed to evaluate HK2 and Beta2AR expression in HCC prognosis, respectively and synergistically.Results: 109 of 155 HCC patients reached the death point, the survival time of HCC patients was 46.23 ± 31.01 months after curative surgical resections of HCC. Kaplan-Meier survival analysis showed that large tumor size (more than 5 cm) (hazard ratio (HR) = 8.42, 95 % confidence interval (CI) = 3.81-18.59, P < 0.0001), advanced TNM stage (III and IV stages) (HR = 2.09, 95%CI = 1.21-3.62, P < 0.001) and AFP more than 20 μg/L (HR = 1.49, 95%CI = 1.02-2.18, P = 0.0302) were predictors for poor prognosis. HK2 and Beta2AR positive expression was detected in 66 (42.58) and 122 (78.71 %) HCC samples respectively. In univariate analysis, HK2(+) (HR = 2.70, 95%CI = 1.76-4.15, P < 0.0001) and Beta2AR(+) (HR = 4.61, 96%CI = 3.14-6.76, P < 0.0001) were associated with poor prognosis. In multivariate analysis, HK2(+) (P < 0.0001) and Beta2AR(+) (P < 0.0001) were also associated with poor prognosis. HK2(+)/Beta2AR(+) in HCC samples had poorer prognosis compared with HK2(-)/Beta2AR(-) in both univariate analysis (HR = 4.69, 95%CI = 2.91-7.57, P < 0.0001) and multivariate analysis (P < 0.0001). HK2(+)/Beta2AR(+) in HCC samples had poorer prognosis compared with HK2(-)/Beta2AR(+) in both univariate analysis (HR = 1.76, 95%CI = 1.17-2.64, P = 0.003) and multivariate analysis (P = 0.004).Conclusion: HK2 and Beta2AR play important roles in HCC progression. HK2 and Beta2AR expression in HCC is correlated positively. Beta2AR may increase HCC invasion and metastasis in collaboration with HK2. HK2 and Beta2AR can predict HCC prognosis both independently and synergistically. [ABSTRACT FROM AUTHOR]

Computed tomographic coronary angiography (CTCA) has prognostic value for early major adverse cardiac events (MACEs) after liver transplantation. However, the association between CTCA and long-term MACEs in liver transplant (LT) recipients remains unknown. We evaluated the association between CTCA and long-term MACEs within 5 years after living donor liver transplantation (LDLT). A total of 628 LDLT recipients who underwent CTCA were analyzed between 2010 and 2012. MACEs were investigated within 5 years after LDLT. The factors associated with long-term MACEs in transplant recipients were evaluated. Only 48 (7.6%) patients developed MACEs. In the Fine and Gray competing risk regression, a coronary artery calcium score (CACS) of >400 combined with obstructive coronary artery disease (CAD) (subdistribution hazard ratio: 5.01, 95% confidence interval: 2.37–10.58, p < 0.001), age (1.05, 1.01–1.10, p = 0.018), diabetes mellitus (2.43, 1.37–4.29, p = 0.002), dyslipidemia (2.45, 1.23–4.70, p = 0.023), and creatinine (1.19, 1.08–1.30, p < 0.001) were independently associated with long-term MACEs. CACS (>400) combined with obstructive CAD may be associated with MACEs within 5 years after LDLT, suggesting the importance of preoperative noninvasive CTCA in LT recipients. The evaluation of coronary artery stenosis on CTCA combined with CACS may have a prognostic value for long-term MACEs in LT recipients. [ABSTRACT FROM AUTHOR]