Development and validation of a novel scoring system based on a nomogram for predicting inadequate bowel preparation.

BACKGROUND AND AIMS: Adequate bowel preparation (BP) is crucial for the diagnosis of colorectal diseases. Identifying patients at risk of inadequate BP allows for targeted interventions and improved outcomes. We aimed to develop a model for predicting inadequate BP based on preparation-related factors. METHODS: Adult outpatients scheduled for colonoscopy between May 2022 and October 2022 were enrolled. One set (N = 913) was used to develop and internally validate the predictive model. The primary predictive model was displayed as a nomogram and then modified into a novel scoring system, which was externally validated in an independent set (N = 177). Inadequate BP was defined as a Boston Bowel Preparedness Scale (BBPS) score of less than 2 for any colonic segment. The model was evaluated by the receiver operating characteristic (ROC) curve, calibration plots, and decision curve analysis (DCA). RESULTS: Independent factors included in the prediction model were stool frequency ≤ 5 (15 points), preparation-to-colonoscopy interval ≥ 5 h (15 points), incomplete dosage (100 points), non-split dose (90 points), unrestricted diet (88 points), no additional water intake (15 points), and last stool appearance as an opaque liquid (0-80 points). The training set exhibited the following performance metrics for identifying BP failure: area under the curve (AUC) of 0.818, accuracy (ACC) of 0.818, positive likelihood ratio (PLR) of 2.397, negative likelihood ratio (NLR) of 0.162, positive predictive value (PPV) of 0.850, and negative predictive value (NPV) of 0.723. In the internal validation set, these metrics were 0.747, 0.776, 2.099, 0.278, 0.866, and 0.538, respectively. The external validation set showed values of 0.728, 0.757, 2.10, 0.247, 0.782, and 0.704, respectively, indicating strong discriminative ability. Calibration curves demonstrated close agreement, and DCA indicated superior clinical benefits at a threshold probability of 0.73 in the training cohort and 0.75 in the validation cohort for this model. CONCLUSIONS: This novel scoring system was developed from a prospective study and externally validated in an independent set based on 7 easily accessible variables, demonstrating robust performance in predicting inadequate BP.

Overexpression of CENPL mRNA potentially regulated by miR-340-3p predicts the prognosis of pancreatic cancer patients.

BACKGROUND: In our previous study it was found that CENPL was overexpressed in hepatocellular carcinoma and significantly predicted patient's prognosis. However, the expression and prognostic value of CENPL in other gastrointestinal tumors remain unknown. Therefore, we investigated the expression and prognostic value of CENPL in esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), pancreatic adenocarcinoma (PAAD), colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ). METHODS: In this study, Oncomine, GEPIA, OncoLnc, TIMER, cBioPortal, miRWalk and ENCORI databases were used to analyze the level of CENPL mRNA, prognostic value and potential regulatory mechanism of CENPL mRNA in tumors. The CENPL expression and clinicopathological data regarding PAAD were from the UCSC Xena database and univariate and multivariate Cox regression analyses were performed using R (Version 3.6.3). Immunohistochemical staining was used to verify the expression of CENPL protein in clinical specimens. Cytoscape (Version: 3.7.2) was used to visualize microRNA (miRNA) that potentially regulates CENPL. RESULTS: Gene differential expression analysis showed that CENPL mRNA was significantly overexpressed in ESCA, STAD, PAAD, COAD and READ (p < 0.01). The overexpression of CENPL mRNA was significantly correlated with the poor prognosis of PAAD patients (p < 0.05). However, there was no significant correlation between the level of CENPL mRNA and the prognosis of ESCA, STAD, COAD and READ patients (p > 0.05). Univariate and multivariate Cox regression analyses suggested that CENPL was a prognostic risk factor for PAAD. The mutation rate of CENPL in PAAD was 2.2% (17/850). There was no significant correlation between the CENPL expression and the infiltration levels of immune cells in PAAD (|Cor|< 0.5). Immunohistochemical staining showed that CENPL was overexpressed in 42% (11/26) of PAAD specimens, which was significantly higher compared with that in the normal tissues. The expression of miR-340-3p and miR-484 in PAAD were significantly lower than in the normal tissues (p < 0.05) and PAAD patients with lower expression of miR-340-3p had poorer prognosis (p < 0.05). CONCLUSION: CENPL potentially regulated by miR-340-3p, is overexpressed in PAAD and predicts patient's prognosis, suggestive of a diagnostic and prognostic value in PAAD patients.

The upregulation of CLGN in hepatocellular carcinoma is potentially regulated by hsa-miR-194-3p and associated with patient progression.

Background: Patients with hepatocellular carcinoma (HCC) have poor prognosis, especially in advanced stages. Targeted therapy is the main treatment for advanced HCC patients, but the optimal targets for HCC remain poorly understood. The main purpose of this study was to identify potential novel prognostic markers and therapeutic targets. Methods: Firstly, differentially expressed genes (DEGs) in HCC were identified from the Gene Expression Omnibus (GEO) database. The expression, significance in prognosis, and potential mechanisms of DEGs were analyzed using GEPIA, TIMER, HPA, Kaplan Meier Plotter, CBioPortal, miRWalk, TargetScan, and ENCORI databases. Immunohistochemical staining was used to determine the protein expression levels of potential candidate genes. Results: The mRNA levels of MND1, STXBP6, and CLGN were significantly increased in HCC (p< 0.01). HCC patients with elevated CLGN mRNA levels had poorer overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and disease-specific survival (DSS) (p < 0.05). Higher MND1 mRNA levels significantly correlated with poorer DFS in HCC patients (p< 0.05). However, there was no significant correlation between STXBP6 expression and prognosis of HCC (p> 0.05). Further analysis revealed that patients with elevated CLGN mRNA expression in advanced pathology stages had poorer prognosis (p< 0.01). In addition, CLGN protein levels were elevated in HCC compared to their levels in normal tissues. The mRNA levels of CLGN had no significant correlation with the abundance of six common tumor infiltrating lymphocytes in HCC (COR < 0.5). Moreover, the mutation rate of CLGN was less than 1% in HCC patients (10/1089). Finally, the expression level of hsa-miR-194-3p in HCC was significantly lower than that in normal tissues (p < 0.05), and prognosis of HCC with low expression of hsa-miR-194 was poor (p < 0.05). Conclusion: The upregulation of CLGN in HCC is significantly associated with poor patient prognosis, especially in the advanced stages, and may be regulated by hsa-miR-194-3p. These findings suggest that CLGN may be closely related to the progression of HCC, and is a potential therapeutic target and prognostic indicator for patients with advanced HCC.

High mRNA Expression of CENPL and Its Significance in Prognosis of Hepatocellular Carcinoma Patients.

Centromere proteins (CENPs) are the main constituent proteins of kinetochore, which are essential for cell division. In recent years, several studies have revealed that several CENPs were aberrantly expressed in hepatocellular carcinoma (HCC). However, numerous centromere proteins have not been studied in HCC. In this study, we used databases of Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), the Kaplan-Meier Plotter, cBioPortal, the Human Protein Atlas (HPA), and TIMER (Tumor Immune Estimation Resource) and immunohistochemical staining of clinical specimens to investigate the expression of 15 major centromere proteins in HCC to evaluate their potential prognostic value. We found that the mRNA levels of 4 out of 15 centromere proteins (CENPL, CENPQ, CENPR, and CENPU) were significantly higher in HCC than in normal tissues, and their mRNA levels were associated with the tumor stages (p values < 0.01). Patients with higher mRNA levels of CENPL had poorer overall survival, progression-free survival, relapse-free survival, and disease-specific survival (p values < 0.05). Furthermore, the higher levels of CENPL mRNA were associated with worse overall survival in males without hepatitis virus infection (p values < 0.05). The protein expression level of CENPL in human HCC tissue was higher than that in normal liver tissue. In addition, the expression of CENPL was positively correlated with the levels of the tumor-infiltrating lymphocytes. The results suggest that the high mRNA expression of CENPL may be a potential predictor of prognosis in HCC patients.

Correlationship between Ki67, VEGF, and p53 and Hepatocellular Carcinoma Recurrence in Liver Transplant Patients.

BACKGROUND AND AIMS: Patients with hepatocellular carcinoma (HCC) who undergo orthotopic liver transplantation (OLT) are at risk for posttransplant tumor recurrence. The aim of this study was to evaluate the correlation between the expression of Ki67, VEGF, and p53 in HCC and clinicopathological characteristics of HCC patients, as well as their predictive value for HCC recurrence after OLT. METHODS: 60 patients who underwent OLT and were found to have HCC in the liver explant. The expression of Ki67, VEGF, and p53 in HCC was detected by immunohistochemistry. RESULTS: Ki67 was associated with the tumor number and the grade of differentiation at baseline. VEGF was associated with the diameter and number of tumors, tumor differentiation, and lymph node metastasis. p53 was associated with the tumor diameter and tumor encapsulation. The expression of Ki67, VEGF, and p53 in HCC was correlated with the tumor recurrence after OLT, respectively. Among them, VEGF was an independent predictor for tumor recurrence after OLT. CONCLUSION: Ki67, VEGF, and p53 are associated with the recurrence of HCC after OLT. VEGF independently predicts the recurrence of HCC.