A non-linear ensemble model-based surgical risk calculator for mixed data from multiple surgical fields.

BACKGROUND: The misestimation of surgical risk is a serious threat to the lives of patients when implementing surgical risk calculator. Improving the accuracy of postoperative risk prediction has received much attention and many methods have been proposed to cope with this problem in the past decades. However, those linear approaches are inable to capture the non-linear interactions between risk factors, which have been proved to play an important role in the complex physiology of the human body, and thus may attenuate the performance of surgical risk calculators. METHODS: In this paper, we presented a new surgical risk calculator based on a non-linear ensemble algorithm named Gradient Boosting Decision Tree (GBDT) model, and explored the corresponding pipeline to support it. In order to improve the practicability of our approach, we designed three different modes to deal with different data situations. Meanwhile, considering that one of the obstacles to clinical acceptance of surgical risk calculators was that the model was too complex to be used in practice, we reduced the number of input risk factors according to the importance of them in GBDT. In addition, we also built some baseline models and similar models to compare with our approach. RESULTS: The data we used was three-year clinical data from Surgical Outcome Monitoring and Improvement Program (SOMIP) launched by the Hospital Authority of Hong Kong. In all experiments our approach shows excellent performance, among which the best result of area under curve (AUC), Hosmer-Lemeshow test ([Formula: see text]) and brier score (BS) can reach 0.902, 7.398 and 0.047 respectively. After feature reduction, the best result of AUC, [Formula: see text] and BS of our approach can still be maintained at 0.894, 7.638 and 0.060, respectively. In addition, we also performed multiple groups of comparative experiments. The results show that our approach has a stable advantage in each evaluation indicator. CONCLUSIONS: The experimental results demonstrate that NL-SRC can not only improve the accuracy of predicting the surgical risk of patients, but also effectively capture important risk factors and their interactions. Meanwhile, it also has excellent performance on the mixed data from multiple surgical fields.

Potential Diagnostic and Prognostic Values of CBX8 Expression in Liver Hepatocellular Carcinoma, Kidney Renal Clear Cell Carcinoma, and Ovarian Cancer: A Study Based on TCGA Data Mining.

Background: Chromobox protein homolog 8 (CBX8), a transcriptional repressor, participates in many biological processes in various carcinomas. Cell differentiation, aging, and cell cycle progression are examples of such processes. It is critical to investigate CBX8 expression and its relationship with clinicopathological characteristics in liver hepatocellular carcinoma (LIHC), kidney renal clear cell carcinoma (KIRC), and ovarian cancer (OV) to investigate CBX8's potential diagnostic and prognostic values. Methods: TCGA and CPTAC databases were used to compare the data between cancer and matched normal tissues on RNA and protein expression profiles and their relevant clinical information to determine the relationship between CBX8 and clinicopathological features. Kaplan-Meier analyses were used to assess CBX8 relationship's with disease-free survival (DFS), relapse-free survival (RFS), and overall survival (OS). The multivariate Cox regression analysis was used to identify independent risk factors which affect prognosis. DNA methylation and genetic changes and their impact on prognoses were evaluated by cBioPortal and MethSurv websites. Spearman's correlation was used to determine the relationship of CBX8 expression with somatic mutation. Tumor immune estimation resource (TIMER) was adopted to investigate the relationship between CBX8 and immune cell infiltration (ICI). CBX8-relevant genes and proteins are analyzed by EnhancedVolcano and STRING databases. The gene set enrichment analysis (GSEA) was performed to investigate the potential functions of CBX8. Results: CBX8 RNA and protein overexpression were confirmed in LIHC, KIRC, and OV (p < 0.05). High CBX8 was significantly related to the clinical features and poor prognoses. The CBX8 genetic alteration rate was 3%. DNA methylation was also associated with prognoses. CBX8 closely interacted with ICI, TMB, MSI, purity, and ploidy. GO analyses revealed that CBX8-associated genes were enriched in biological processes, cell cycle regulation, and molecular functions. KEGG analyses exhibited that CBX8 was gathered in signaling pathway regulation. GSEA revealed that cell cycle, DNA replication, and Wnt signaling pathways were differentially enriched in the high CBX8 expression group. Conclusions: CBX8 could be a potential diagnostic and prognostic biomarker for LIHC, KIRC, and OV cancers.

Prediction of residual/recurrent disease by HPV genotype after loop excision procedure for high-grade cervical intraepithelial neoplasia with negative margins.

AIMS: This study aims to evaluate whether the preconisation of high-risk human papillomavirus (HR-HPV) genotype and multiple HPV infection is predictive for residual/recurrent disease during the follow-up of high-grade cervical intraepithelial neoplasia (CIN) treated by loop electrosurgical excision procedure (LEEP) with negative margins. METHODS: Two hundred and thirty-six women (mean age 37; range 20-61) with CIN2/3 treated by LEEP conisation with negative margins confirmed by pathology examination of the surgical specimen were included. The cervical cells for HPV genotype testing by the polymerase chain reaction (PCR) were collected before, and 6, 12, 24 months after treatment, respectively. HPV genotype and multiple HPV infection were evaluated as possible predictors of residual/recurrent disease. RESULTS: Residual/recurrent disease was demonstrated by colposcopy-guided biopsy in 62 patients (26.3%) who underwent loop conisation with negative margins. Preoperative infection with either HPV16 (P = 0.007), HPV18 (P = 0.000), HPV33 (P = 0.001) or HPV45 (P = 0.019) was associated with higher rates of residual/recurrent lesions after conisation with negative margins. Preoperative infection with multiple HPV types was associated with the highest rate of residual/recurrent lesions compared with infection with single HPV type and HPV-negative cases (χ2 = 16.599, P < 0.001). CONCLUSIONS: Results demonstrate that the presence of HPV-16, 18, 33 and 45, as well as multiple HPV types pre-LEEP, is associated with higher rates of residual/recurrent disease after LEEP.

Association of iRhom1 and iRhom2 expression with prognosis in patients with cervical cancer and possible signaling pathways.

Several proteins in the iRhom family function as oncogenic regulators in certain cancers. However, the function of these proteins in cervical cancer (CC) is unknown. The relationship of iRhom1 and iRhom2 expression with the clinicopathological features and prognosis of patients with CC was investigated, and their possible molecular mechanisms were examined using in vitro experiments. The expression of iRhom1 and iRhom2 in CC samples of 83 patients was determined by immunohistochemistry (IHC), and the associations of their expression with the clinicopathological features of patients were determined. The relationship of iRhom1, iRhom2, and Ki­67 expression with survival rates was determined using Kaplan­Meier analysis and Cox regression analyses. HeLa cells were analyzed using MTT assays, cell cycle analysis, and apoptosis assays. The results revealed that CC tissues had higher levels of iRhom1 and iRhom2 than adjacent normal tissues. Increased expression of iRhom1, iRhom2, and K­i67 was significantly associated with tumor stage, size, and parametrium invasion. High expression of iRhom1, iRhom2 and Ki­67 was correlated with poor outcomes. Cancer stage and iRhom2 expression were independent prognostic indicators of CC. Knockdown of iRhom1 and iRhom2 in HeLa cells inhibited cell proliferation, promoted the G1 phase and relieved S­phase arrest, and induced apoptosis. Genomic microarray analysis indicated that iRhom2 knockdown altered several pathways with roles in oncogenesis, including the expression of five genes in the Wnt/ß­catenin pathway. Western blotting in HeLa cells revealed that iRhom1 knockdown significantly suppressed the expression of ß­catenin, Myc, p­EGFR and TGFBR2, and increased the expression of FAS; iRhom2 knockdown significantly suppressed the expression of ß­catenin, GSK3ß, p­EGFR and Myc. These results were consistent with the genomic microarray data. Collectively, the results indicated that iRhom1 and iRhom2 may function as oncogenes in CC and are potential therapeutic targets.

[Enhanced anti-tumor effect of dendritic cells modified by CIITA gene in hepatocellular carcinoma-bearing mice].

AIM: To study the effect of MHC class II transactivator(CIITA ) on the expression of MHC class I/II molecules, CD80 and CD86 molecules on dendritic cells(DCs), and explor the use of DCs modified by CIITA gene in the biotherapy of tumors. METHODS: We transfected the mouse CIITA gene by lipofectamine into DCs drived from mouse bone marrow. The expression of MHC class I/II, CD80, and CD86 molecules was detected by flow cytometry. 40 mice bearing hepatcellular carcinoma were divided into 4 groups: group 1 were treated with a para-tumor injection of PBS, group 2 DCs, group 3 modified DCs, and group 4 modified DCs pulsed with H22 tumor antigen. Then the anti-tumor effect of DCs modified by mCIITA was evaluated by measuring the tumor size. RESULTS: After transfection of mCIITA, the expression rate of MHC class I/II molecules of DCs increased from 74.2%/66.7% to 93.6%/91.4%, and that of CD80/CD86 increased from 52.3%/60.5% to 89.7%/91.5%. After immunization, the growth of H22 tumors in group 4 mice was significantly inhibited compared with that in other three groups (P<0.05 at 3, 4, 5, 6, and 7 weeks versus groups 1, 2; P<0.05 at 5, 6, 7 weeks versus group 3). CONCLUSION: The expression of MHC I/II, CD80 and CD86 on DCs was regulated markedly by transfection of mCIITA. mCIITA transfection also enhanced the anti-tumor effect of DCs. Our results provided a new method for biotherapy of tumors with DCs.