Risk prediction of second primary malignancies in patients after rectal cancer: analysis based on SEER Program.

BACKGROUND: This study will focus on exploring the clinical characteristics of rectal cancer (RC) patients with Second Primary Malignancies (SPMs) and constructing a prognostic nomogram to provide clinical treatment decisions. METHODS: We determined the association between risk factors and overall survival (OS) while establishing a nomogram to forecast the further OS status of these patients via Cox regression analysis. Finally, we evaluated the performance of the prognostic nomogram to predict further OS status. RESULTS: Nine parameters were identified to establish the prognostic nomogram in this study, and, the C-index of the training set and validation set was 0.691 (95%CI, 0.662-0.720) and 0.731 (95%CI, 0.676-0.786), respectively. The calibration curve showed a high agreement between the predicted and actual results, and the receiver operating characteristic (ROC) curves verified the superiority of our model for clinical usefulness. In addition, the nomogram classification could more precisely differentiate risk subgroups and improved the discrimination of SPMs' prognosis. CONCLUSIONS: We systematically explored the clinical characteristics of SPMs after RC and constructed a satisfactory nomogram.

TMEM158 promotes pancreatic cancer aggressiveness by activation of TGFß1 and PI3K/AKT signaling pathway.

Pancreatic cancer (PC) is one of the most deadly digestive cancers world-wide, with a dismal five-year survival rate of <8%. Upregulation of transmembrane protein 158 (TMEM158) is known to facilitate the progression of several carcinomas. However, little is known concerning the potential roles of TMEM158 in PC. Herein, we first found that TMEM158 was significantly upregulated in PC samples as well as PC cell lines. The overexpression of TMEM158 was significantly correlated with advanced clinicopathologic features (including tumor size, TNM stage, and blood vessel invasion) and poorer prognosis of patients with PC in clinic. Evidenced based on a series of loss- and gain-of-function assays uncovered that TMEM158 enhanced PC cell proliferation, migration, and invasion by stimulating the progression of cell cycle, epithelial-mesenchymal transition, and MMP-2/9 production. Furthermore, mechanism-related investigations disclosed that activation of TGFß1 and PI3K/AKT signal might be responsible for TMEM158-triggered PC aggressiveness. Collectively, TMEM158 was upregulated in PC and promoted PC cell proliferation, migration, and invasion through the activation of TGFß1 and PI3K/AKT signaling pathways, highlighting its potential as a tumor promoter and a therapeutic target for PC.

PARP14 promotes the proliferation and gemcitabine chemoresistance of pancreatic cancer cells through activation of NF-κB pathway.

Pancreatic cancer (PC) is the most fatal gastrointestinal malignancy in the world, with a 5-year relative survival of only 8%. Poly(ADP-ribose) polymerase (PARP)14, a member of the macro-PARP subfamily proteins, has been reported to participate in various biologic and pathologic processes in multiple cancers. The roles and underlying molecular mechanisms of PARP14 in PC carcinogenesis, however, remain to be elucidated. In this study, we for the first time discovered that PARP14 was highly expressed in human primary PC specimens and significantly correlated with poor patient prognosis. Using loss-of-function studies in vitro and in vivo, we showed that the knockdown of PARP14 led to enhanced apoptosis, repressed proliferation, and gemcitabine (GEM) resistance of PC cells. Further investigations revealed that PARP14 was significantly overexpressed in GEM-resistant PC cells (SW1990/GZ). And silencing of PARP14 significantly reversed the GEM resistance of SW1990/GZ cells. To the mechanism, PARP14 could stimulate PC progression by the activation of nuclear factor-κB (NF-κB) signaling pathway. And inhibition of NF-κB signal could significantly reverse PARP14-overexpression triggered PC carcinogenesis. In conclusion, PARP14 could promote PC cell proliferation, antiapoptosis, and GEM resistance via NF-κB signaling pathway, highlighting its potential role as a therapeutic target for PC.

A non-synonymous SNP in the NOS2 associated with septic shock in patients with sepsis in Chinese populations.

Sepsis represents a systemic inflammatory response to infection and its sequelae include severe sepsis, septic shock, multiple organ dysfunction syndrome (MODS) and death. Studies in mice and humans indicate that the inducible nitric oxide synthase (iNOS, NOS2) plays an important role in the development of sepsis and its sequelae. It was reported that several single nucleotide polymorphisms (SNPs) within NOS2 could influence the production or activity of NOS2. In this study, we assessed whether SNPs within NOS2 gene were associated with severity of sepsis in Chinese populations. A case-control study was conducted, which included 299 and 280 unrelated patients with sepsis recruited from Liaoning and Jiangsu provinces in China, respectively. Six SNPs within NOS2 were genotyped using Sequenom MassARRAY system. The associations between the SNPs and risk of sepsis complications were estimated by a binary logistic regression model adjusted for confounding factors. Functional assay was performed to assess the biological significance. The GA + AA genotype of a non-synonymous SNP in the exon 16 of NOS2 (rs2297518: G>A) was significantly associated with increased susceptibility to septic shock compared with GG genotype in Liaoning population (OR = 3.29, 95% CI = 1.40-7.72, P = 0.0047). This association was confirmed in the Jiangsu population (OR = 3.49, 95% CI = 1.57-7.79, P = 0.0019). Furthermore, the functional assay performed in the immortalized lymphocyte cell lines indicated that the at-risk GA genotype had a tendency of higher NOS2 activity than the GG genotype (P = 0.32). Our findings suggest that the NOS2 rs2297518 may play a role in mediating the susceptibility to septic shock in patients with sepsis in Chinese populations.

A nomogram model based on the combination of the systemic immune-inflammation index and prognostic nutritional index predicts weight regain after laparoscopic sleeve gastrectomy.

BACKGROUND: The high rate of weight regain after laparoscopic sleeve gastrectomy is a great challenge. The systemic immune-inflammation index (SII; calculated by neutrophils, lymphocytes, and platelets) and prognostic nutritional index (PNI; calculated by albumin and lymphocytes) are widely used as prognostic factors in various diseases. OBJECTIVES: The objective of this study was to investigate independent the independent risk factors associated with weight regain in patients after laparoscopic sleeve gastrectomy. SETTING: A single-center retrospective study. METHODS: Weight regain was defined as the percentage of increase in body weight ≥10% in comparison with the nadir weight postoperatively. Eligible patients admitted to the bariatric center of our hospital were consecutively enrolled and grouped according to the occurrence of weight regain within 5 postoperative years. Univariate and multivariate logistic regression analyses were performed to assess potential risk factors. A nomogram model containing the risk factors was then constructed and evaluated by R. RESULTS: A total of 217 patients were enrolled, and 87 (40.1%) patients experienced weight regain. Univariate and logistic regression analyses indicated that depression (odds ratio [OR]: 2.51, 95% confidence interval [CI]: 1.20-5.22, P = .015), psychological counseling (OR: 2.27, 95% CI: 1.20-4.33, P = .017), preoperative C-reactive protein (OR: 2.20, 95% CI: 1.18-4.13, P = .012), and combination of SII-PNI scores (OR: .45, 95% CI: .31-.67, P < .001) were 4 independent risk factors for postoperative weight regain in laparoscopic sleeve gastrectomy patients. The area under the curve of the constructed nomogram model for predicting weight regain was .706. CONCLUSIONS: This study concluded that the combination of the SII-PNI was an independent risk factor for weight regain and that the nomogram model based on the combination of the SII-PNI had a good predictive value.

LEM domain containing 1 promotes pancreatic cancer growth and metastasis by p53 and mTORC1 signaling pathway.

Pancreatic cancer (PC) is a common type of malignancy originating from the epithelium of the pancreatic duct, with the most lethal feature and worst prognosis. LEM domain containing 1 (LEMD1) is overexpressed in multiple tumor tissues and plays a key role in cancer carcinogenesis and progression. However, little is known about the potential of LEMD1 in PC. In this study, we explored the clinical values, as well as the potential roles and mechanisms of LEMD1 in PC. We, for the first time, showed that LEMD1 was upregulated in PC and negatively correlated with the overall and disease-free survival of patients with PC. Of the function, LEMD1 knockdown inhibited cancer cell growth, migration and invasion, while LEMD1 overexpression promoted tumor aggressiveness. The tumor-promoting influences of LEMD1 in PC were also proved by in vivo assays. Mechanistically, GSEA identified that LEMD1 promoted PC aggressiveness, as well as affecting cell cycle dysregulation and apoptosis resistance, by p53 suppression and the activation of the mTORC1 signal pathway. In short, LEMD1 could serve as a valuable prognostic candidate and a potential therapeutic target of PC.Abbreviations: ATCC: American Type Culture Collection; CCK-8: Cell counting kit 8; CDK: Cyclin-dependent kinases; CTA: Cancer-testis antigen; DMEM: Dulbecco's Modified Eagle's Medium; ECL: enhanced chemiluminescence; FBS: Fetal bovine serum; GEO: Gene Expression Omnibus; LEMD1: LEM domain containing 1; mTOR: mammalian target of rapamycin; NC: Negative control; PC: Pancreatic cancer; PVDF: Polyvinylidene difluoride membranes; qRT-PCR: Quantitative real-time polymerase chain reaction; SDS-PAGE: Sodium dodecyl sulfate polyacrylamide gel electrophoresis; SD: Standard deviation; SKP2: S-Phase kinase-associated protein 2; TAA: Tumor-associated antigen; TBST: Tris-buffered Saline Tween-20; TCGA: The Cancer Genome Atlas.

Papillary Thyroid Microcarcinoma: A Nomogram Based on Clinical and Ultrasound Features to Improve the Prediction of Lymph Node Metastases in the Central Compartment.

Background: Accurate preoperative identification of central lymph node metastasis (CLNM) is essential for surgical protocol establishment for patients with papillary thyroid microcarcinoma (PTMC). We aimed to develop a clinical and ultrasound characteristics-based nomogram for predicting CLNM. Methods: Our study included 399 patients who were pathologically diagnosed with PTMC between January 2011 and June 2018. Clinical and ultrasound features were collected for univariate and multivariate analyses to determine risk factors of CLNM. A nomogram comprising the prognostic model to predict the CLNM was established, and internal validation in the cohort was performed. The Cox regression model was used to determine the risk factors for recurrence-free survival (RFS) and cumulative hazard was calculated to predict prognosis. Results: Three variables of clinical and US features as potential predictors including sex (odd ratio [OR] = 1.888, 95% confidence interval [CI], 1.160-3.075; P =0.011), tumor size (OR = 1.933, 95% CI, 1.250-2.990; P =0.003) and ETE (OR = 6.829, 95% CI, 3.250-14.350; P <0.001) were taken into account. The predictive nomogram was established by involving all the factors above used for preoperative prediction of CLNM in patients with PTMC. The nomogram showed excellent calibration in predicting CLNM, with area under curves (AUC) of 0.684 (95% CI, 0.635 to 0.774). Furthermore, tumor size, multifocality, presence of ETE, vascular invasion, and CLNM were the significant factors related to the RFS. Conclusion: Through this easy-to-use nomogram by combining clinical and US risk factor, the possibility of CLNM can be objectively quantified preoperatively. This prediction model may serve as a useful clinical tool to help clinicians determine an individual's risk of CLNM in PTMC, thus make individualized treatment plans accordingly.

Identification of prognostic significance of BIRC5 in breast cancer using integrative bioinformatics analysis.

AIMS: Baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) plays vital roles in carcinogenesis by influencing cell division and proliferation and by inhibiting apoptosis. However, the prognostic significance of BIRC5 remains unclear in breast cancer. METHODS: BIRC5 expression and methylation status were evaluated using the Oncomine and The Cancer Genome Atlas (TCGA) databases. The relevance between BIRC5 and different clinicopathological features as well as survival information was analyzed using the bc-GenExMiner database and Kaplan-Meier Plotter. BIRC5-drug interaction network was obtained using the Comparative Toxicogenomics Database. RESULTS: Based on the results from databases and own hospital data, BIRC5 was higher expressed in different breast cancer subtypes compared with the matched normal individuals. Hormone receptors were negatively correlated with BIRC5 expression, whereas the Scarff-Bloom-Richardson (SBR) grade, Nottingham Prognostic Index (NPI), human epidermal growth factor receptor-2 (HER-2) status, basal-like status, and triple-negative status were positively related to BIRC5 level in breast cancer samples with respect to normal tissues. High BIRC5 expression was responsible for shorter relapse-free survival, worse overall survival, reduced distant metastasis free survival, and increased risk of metastatic relapse event. BIRC5-drug interaction network indicated that several common drugs could modulate BIRC5 expression. Furthermore, a positive correlation between BIRC5 andcell-division cycle protein 20 (CDC20) gene was confirmed. CONCLUSION: BIRC5 may be adopted as a promising predictive marker and potential therapeutic target in breast cancer. Further large-scale studies are needed to more precisely confirm the value of BIRC5 in treatment of breast cancer.