ITGA2 overexpression inhibits DNA repair and confers sensitivity to radiotherapies in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a dismal disease with a 5-year survival rate of less than 10%, despite the recent advances in chemoradiotherapy. The sensitivity of the PDAC patients to chemoradiotherapy varies widely, especially to radiotherapy, suggesting the need for more elucidation of the underlying mechanisms. In this study, a novel function of the nuclear ITGA2, the alpha subunit of transmembrane collagen receptor integrin alpha-2/beta-1, regulating the DNA damage response (DDR), was identified. First, analyzing The Cancer Genome Atlas (TCGA) PDAC data set indicated that the expression status of ITGA2 was negatively correlated with the genome stability parameters. The study further demonstrated that ITGA2 specially inhibited the activity of the non-homologous end joining (NHEJ) pathway and conferred the sensitivity to radiotherapy in PDAC by restraining the recruitment of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to Ku70/80 heterodimer during DDR. Considering the overexpression of ITGA2 and its associated with the poor prognosis of PDAC patients, this study suggested that the ITGA2 expression status could be used as an indicator for radiotherapy and DNA damage reagents, and the radiotherapy in combination with the overexpression of ITGA2 might be a viable treatment strategy for the PDAC patients.

UBE3A activates the NOTCH pathway and promotes esophageal cancer progression by degradation of ZNF185.

Background: Esophageal cancer is the sixth-most common fatal malignant tumor worldwide. Little is known regarding the genetic drivers that influence targeted therapy outcomes in patients with esophageal cancer. Exploring the pathogenesis of this lethal tumor could provide clues for developing appropriate therapeutic drugs. Ubiquitin-protein ligase E3A (UBE3A) reportedly promotes or suppresses various types of malignant tumors. However, the cancer-related role of UBE3A in esophageal cancer remains unclear. Methods: The relationship of UBE3A with the clinicopathological features of pancreatic tumors was bioinformatically investigated in the TCGA dataset. The protein levels of UBE3A and ZNF185 were assessed by Western blot and immunohistochemistry. The role of UBE3A and ZNF185 in esophageal cancer growth was assessed by MTS assays, colony formation assays, and experiments in mouse xenograft models. The interaction between UBE3A and ZNF185 was investigated by co-immunoprecipitation. The relationship between UBE3A, ZNF185, and NOTCH signaling pathway was explored by Western blot and quantitative real-time PCR. Results: We found that UBE3A was upregulated in patients with esophageal cancer and enhanced the cellular progression of esophageal cancer. Moreover, we found that UBE3A degraded ZNF185 in esophageal cancer. Additionally, ZNF185 suppressed the progression of esophageal cancer by inactivating the NOTCH pathway. Conclusions: These data demonstrated that aberrant expression of UBE3A led to enhanced progression of esophageal cancer through the ZNF185/NOTCH signaling axis. Therefore, UBE3A might be an ideal therapeutic candidate for esophageal cancer.

The m6A-Related mRNA Signature Predicts the Prognosis of Pancreatic Cancer Patients.

N6-methyladenosine (m6A) has an important epitranscriptomic modification that controls cancer self-renewal and cell fate. The addition of m6A to mRNA is a reversible modification. The deposition of m6A is encoded by a methyltransferase complex involving three homologous factors, jargonized as "writers," "erasers," and "readers." However, their roles in pancreatic adenocarcinoma (PAAD) are underexploited. With the use of The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, we provided an mRNA signature that may improve the prognostic prediction of PAAD patients based on the genetic status of m6A regulators. PAAD patients with genetic alteration of m6A regulators had worse disease-free and overall survival. After comparing PAAD groups with/without genetic alteration of m6A regulators, we identified 196 differentially expressed genes (DEGs). Then, we generated a 16-mRNA signature score system through least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Multivariate cox regression analysis demonstrated that a high-risk score significantly correlates with poor prognosis. Moreover, time-dependent receiver operating characteristic (ROC) curves revealed it was effective in predicting the overall survival in both training and validation sets. PAH, ZPLD1, PPFIA3, and TNNT1 from our signature also exhibited an independent prognostic value. Collectively, these findings can improve the understanding of m6A modifications in PAAD and potentially guide therapies in PAAD patients.

A new scoring system can be applied to predict the organ failure related events in acute pancreatitis accurately and rapidly.

AIM: To establish a new scoring system to predict the organ failure (OF)-related events in acute pancreatitis (AP) with high accuracy and rapidity. BACKGROUND: AP is a complicated immunological response that leads to multiple organ failure，but no single scoring system has so far effectively predicted the severity of OF-related events in AP. METHODS: The research utilized a retrospective study including 1076 AP patients to establish the new scoring system and a prospective study of another 138 patients to verify it. All the laboratory parameters were measured at admission (within 72 h of disease onset). Dunnett'T3 test, univariate and multivariate ordinal logistic regressions were performed. ROC curves were drawn to calculate the cut-off value of the chosen factors and to validate the predictive value of the system. RESULTS: Lactate dehydrogenase (LDH), creatinine (Cr), albumin (ALB) and calcium (Ca2+) made up the new system. The Area Under the Curve (AUC) of the system for OF was 0.904, and for persistent organ failure (POF) was 0.893 while that for death cases was 0.969. As a result, patients who scored 'zero' seemed to recover soon, who received a score '1-4' might have transient organ failure (TOF) but not POF. When the score was over 5, it was probable that patients would suffer POF, and even die if it exceeded 9. The test of the new scoring system proved it conducted well. CONCLUSION: The new scoring system can accurately and promptly predict the OF-related events in AP.

Prolonged survival time with surgical therapy in different types of thymoma: an analysis based on Surveillance Epidemiology and End Results Database.

BACKGROUND: Thymoma is the most common tumor within the anterior mediastinum though it is still a rare tumor disease. Surgery is considered to be one of the most important treatment methods for it, while radiotherapy and platinum-based chemotherapy are also in use. Based on the Surveillance, Epidemiology and End Results (SEER) database, we conducted our research and determined the value of operation in the treatment of thymoma. METHODS: In total, 1,587 patients with thymoma were selected out from the database. We grouped them according to type and stage of thymoma. We used cox-regression analysis to selected meaningful factors. Kaplan-Meier method was used for survival analysis. RESULTS: The mean survival times of patients with type A, B, C thymoma were 130.79, 123.81, 77.18 months orderly. Among all 1,587 patients, the mean survival time of those treated with surgery was 124.92 months, while it was 65.03 months for those without surgery treatment (P<0.05). Within each group of patients with the same kind of and same stage thymoma, who got surgical treatment had a longer survival period (P<0.05). CONCLUSIONS: Type c thymoma had the worst prognosis. Patients who received surgical treatment had longer survival time. And it didn't matter what type or what stage of thymoma.

The product value of serum albumin and prothrombin time activity could be a useful biomarker for severity prediction in AP: An ordinal retrospective study.

AIM: To appraise the predictive function of 'the product value of serum albumin and prothrombin time activity' (PAA) on admission for the organ failure related events of acute pancreatitis (AP). BACKGROUND: 789 patients with AP were included in this retrospective study. 468 patients generated transient organ failure (TOF). 242 were diagnosed with persistent organ failure (POF), of which 63 patients died. STUDY: All the values of laboratory parameters were measured upon admission to hospital. Dunnett'T3 test, Uni- and multi-variate ordinal logistic regression were used. ROC curve was utilized to evaluate the ultimate predictive values. RESULTS: Among the patients with 4 different levels of severity of acute pancreatitis, PAA observably reduced as the disease aggravated (32.20 vs 29.56 vs 23.54 vs 17.89). PAA was also an independent risk factor for the aggravation of AP (OR: 0.873, 95% CI: 0.848, 0.899; p < 0.01). The Area Under the Curve (AUC) of PAA for OF was 0.828 (0.783, 0.872), 0.828 for POF (0.790, 0.865) and 0.905 for death cases (0.862, 0.948). CONCLUSION: The product value of serum albumin and prothrombin time activity is a good predictor of the severity, especially the events related to organ failure of acute pancreatitis.

Prognostic value of progesterone receptor in solid pseudopapillary neoplasm of the pancreas: evaluation of a pooled case series.

BACKGROUND: The role of progesterone receptor (PR) has been reported in a series of pancreatic cysts. However, the relationship between PR and prognosis of solid pseudopapillary neoplasm of the pancreas (SPNP) has not been elucidated so far. The aim of our study was to evaluate the prognostic value of PR in SPNP. METHODS: A total of 76 patients with SPNP treated in our institution from January 2012 to December 2017 were included. Demographic parameters, laboratory data, pathologic information and clinical outcomes were analyzed by the use of survival analysis. In addition, a pooled case series was performed to evaluate the results. RESULTS: The institutional data included 76 patients (17 male and 59 female) ranging from 8 to 90 years (median, 30 years) in age. Kaplan-Meier survival analysis confirmed negative PR result was significantly associated with poorer disease-free survival (DFS) and disease-specific survival (DSS) (both P < 0.001). In the pooled analysis, a total of 62 studies comprising 214 patients with SPNP were included. After multivariable cox analysis, negative PR result remained an independent prognostic factor for SPNP (DFS HR: 14.50, 95% CI: 1.98-106.05, P = 0.008; DSS HR: 9.15, 95% CI: 1.89-44.17, P = 0.006). CONCLUSION: Our results indicated the role of PR in predicting adverse outcome of patients with SPNP and negative PR result may serve as a potential prognostic factor.

Correction: B7-H4 as an independent prognostic indicator of cancer patients: a meta-analysis.

[This corrects the article DOI: 10.18632/oncotarget.18566.].

B7-H4 as an independent prognostic indicator of cancer patients: a meta-analysis.

The expression of B7-H4 was observed in a variety of tumors, however the prognostic value in cancer was still controversial. Therefore, we conducted this meta-analysis to explore the potential role of B7-H4 in cancer prognostic prediction. Twenty-seven studies including 3771 patients were brought into the analysis according to the inclusion and exclusion criteria. The pooled results demonstrated that elevated B7-H4 predicted a poor OS (HR = 1.93, 95% CI 1.71-2.18, P < 0.001) and DFS (HR = 1.84, 95% CI 1.46-2.33, P < 0.001). Subgroup analysis showed that races, tumor types, sample sources, analysis types, sources of HR and sample sizes exhibited non-significant distinctions with OS (PS = 0.878, PS = 0.143, PS = 0.613, PS = 0.639, PS = 0.48 and PS = 0.528, respectively). PubMed, Embase and the Cochrane Library were searched up to April 7, 2017, to recognize the available studies for assessing the association between B7-H4 and cancer patients' outcome. We extracted the hazard ratio (HR), relative ratio (RR), odds ratio (OR) with their 95% confidence interval (CI) for overall survival (OS) or disease-free survival (DFS) as the effect size (ES) for the analysis. This meta-analysis demonstrates high expression of B7-H4 is a negative correlation with the outcome of cancer patients.

Decreased high density lipoprotein cholesterol is an independent predictor for persistent organ failure, pancreatic necrosis and mortality in acute pancreatitis.

High density lipoprotein cholesterol (HDL-C) has been reported as a significant indicator of systemic inflammation. The association underlying HDL-C and persistent organ failure (POF), pancreatic necrosis (PNec) and mortality in acute pancreatitis (AP) has not been evaluated. From 2007 to 2016, consecutive AP patients with admission lipid profiles assessment were included in this study. The association of HDL-C value and other lipids with outcomes was explored with Cox proportional regression models, which were adjusted for confounding factors. 1131 consecutive AP patients were clinically eligible. Overall, 17.9% of the patients developed with POF, 27.1% experienced PNec, and 6.7% died during hospitalization. Lower HDL-C median (<1.06 mmol/L) was identified as an independent prognostic factor of the outcomes. Moreover, there was a positive trend for the association across increasing HDL-C quartiles and POF, PNec and mortality after multivariable analysis (p values were <0.001, <0.001 and 0.043, respectively). The AUC of HDL-C for the outcomes were comparable to that of Ranson score for diagnosing POF (0.778 vs. 0.678; P < 0.001), PNec (0.734 vs. 0.701; P = 0.143) and mortality (0.768 vs. 0.745; P = 0.516). Decreased HDL-C value is an independent risk factor for the incidence of POF, PNec and in-hospital mortality in AP.

Serum albumin, a good indicator of persistent organ failure in acute pancreatitis.

BACKGROUND: To evaluate the predictive value of serum albumin (ALB) for persistent organ failure (POF) in acute pancreatitis (AP). METHODS: We selected 158 patients with AP in this retrospective study from Jan.1st, 2015 to Dec.31st, 2015. Forty-six patients were diagnosed with POF. All the values of laboratory parameters were measured upon admission to hospital. And 48 h after admission, we examined serum albumin of each patient again, called 'ALB2'. Uni-and multi-variate logistic regression were used to evaluate the impact of ALB to predict POF. RESULTS: The median age of the whole population was 48 years and 53.8% were male. The admission-time albumin of AP patients with POF was distinctly lower than patients without POF (28.9 (25.3-33.1) g/L vs. 38.5 (34.0-40.1) g/L, p < 0.001). In uni-variate analysis, WBC, PT, GLU, LDH, ALB, ALB2, BUN, Ca, HDL-C and Ranson were significantly associated with POF. After multivariate regression, ALB remained an independent prognostic factor for POF in AP (OR: 0.748, 95%CI: 0.645-0.868; p < 0.05). The AUC for ALB is 0.873 (0.808, 0.938), even larger than that for Ranson, 0.845 (0.634, 0.913). CONCLUSIONS: We identified serum albumin predictive to persistent organ failure in acute pancreatitis.

Platelet Distribution Width Levels Can Be a Predictor in the Diagnosis of Persistent Organ Failure in Acute Pancreatitis.

PURPOSE: The change of serum platelet indices such as platelet distribution width (PDW) has been reported in a series of inflammatory reaction and clinical diseases. However, the relationship between PDW and the incidence of persistent organ failure (POF) in acute pancreatitis (AP) has not been elucidated so far. MATERIALS AND METHODS: A total of 135 patients with AP admitted within 72 hours from symptom onset of AP at our center between December 2014 and January 2016 were included in this retrospective study. Demographic parameters on admission, organ failure assessment, laboratory data, and in-hospital mortality were compared between patients with and without POF. Multivariable logistic regression analyses were utilized to evaluate the predictive value of serum PDW for POF. RESULTS: 30 patients were diagnosed with POF. Compared to patients without POF, patients with POF showed a significantly higher value of serum PDW on admission (14.88 ± 2.24 versus 17.60 ± 1.96%, P < 0.001). After multivariable analysis, high PDW level remained a risk factor for POF (odds ratio 39.42, 95% CI: 8.64-179.77; P < 0.001). A PDW value of 16.45% predicted POF with an area under the curve (AUC) of 0.870, a sensitivity with 0.867, and a specificity with 0.771, respectively. CONCLUSIONS: Our results indicate that serum PDW on admission could be a predictive factor in AP with POF and may serve as a potential prognostic factor.