Development and Validation of Subsyndromal Delirium Prediction Model in Patients With Advanced Malignant Tumor: A Case-Control Study.

BACKGROUND: Subsyndromal delirium (SSD) is a clinical manifestation between delirium and nondelirium. There is no established guideline for diagnosing SSD, with a few different tools used for diagnosis. OBJECTIVES: To construct and verify the risk prediction model for subdelirium syndrome in patients with advanced malignant tumors and explore its application value in risk prediction. METHODS: A total of 455 patients admitted to the Oncology Department in a tertiary grade A hospital in Hengyang City were recruited from December 2020 to May 2021. They were selected as the modeling group. The model was constructed by logistic regression. A total of 195 patients with advanced malignant tumors from June 2021 to July 2021 were selected to validate the developed model. RESULTS: The predictors incorporated into the model were opioids (odds ratio [OR], 1.818), sleep disorders (OR, 1.783), daily living ability score (OR, 0.969), and pain (OR, 1.810). In the modeling group, the Hosmer-Lemeshow goodness-of-fit test was P = .113, the area under the receiver operating characteristic curve was 0.884, the sensitivity was 0.820, and the specificity was 0.893. In the validation group, the Hosmer-Lemeshow goodness-of-fit test P = .108, the area under the receiver operating characteristic curve was 0.843, the Yuden index was 0.670, the sensitivity was 0.804, and the specificity was 0.866. CONCLUSIONS: This model has excellent precision in the risk prediction of subdelirium in patients with advanced malignant tumors. IMPLICATIONS FOR PRACTICE: The model we developed has a guiding significance for specialized tumor nurses to care for patients with advanced malignant tumors and improve their quality of life.

Circ_0087862 promotes tumorigenesis and glycolysis in colorectal cancer by sponging miR-296-3p to regulate PGK1 expression.

BACKGROUND: Circular RNAs (circRNAs) exert crucial roles in tumor progression of multiple cancers, including colorectal cancer (CRC). However, the functions of most circRNAs are not been fully elucidated. In this study, the role and mechanism of circ_0087862 in CRC were investigated. METHODS: The expression of circ_0087862, microRNA-296-3p (miR-296-3p) and phosphoglycerate kinase 1 (PGK1) was detected by quantitative real-time PCR (qRT-PCR). Cell Counting Kit-8 (CCK-8) assay and 5-ethynyl-2'-deoxyuridine (EdU) assay were used to assess cell proliferation. Flow cytometry was employed to analyze cell apoptosis. Transwell assay was employed to evaluate cell invasion. Western blot assay was employed to detect the level of related protein markers and PGK1. The glucose consumption, lactate production were tested by corresponding kits. The relationship between miR-296-3p and circ_0087862 or PGK1 was verified by dual-luciferase reporter assay or RNA immunoprecipitation (RIP) assay. The in vivo function of circ_0087862 was examined by xenograft mice model. RESULTS: The expression levels of circ_0087862 and PGK1 were up-regulated in CRC tissues and cells, while miR-296-3p was down-regulated. Circ_0087862 silencing suppressed cell proliferation, invasion and glycolysis and promoted cell apoptosis in CRC cells. Circ_0087862 targeted miR-296-3p in CRC cells. MiR-296-3p inhibition reversed circ_0087862 silencing-mediated inhibition effect on cell proliferation, invasion and glycolysis, as well as the promotion effect on cell apoptosis. PGK1 was a target of miR-296-3p, and the overexpression of PGK1 attenuated miR-296-3p-mediated tumor suppression effect on CRC progression. Moreover, knockdown of circ_0087862 inhibited tumorigenesis in vivo. CONCLUSION: Circ_0087862 promoted CRC progression via miR-296-3p/PGK1 axis and might act as a potential target for CRC therapy.

Risk model and factors for prediction of response to neoadjuvant chemotherapy in patients with advanced gastric cancer-a two-center cohort study.

OBJECTIVE: Due to inconsistency in neoadjuvant chemotherapy (NACT) response in advanced gastric cancer (GC), the indications remain the source of controversy. This study focused on identifying factors related to NACT chemosensitivity and providing the best treatment for GC cases. METHODS: Clinical data in 867 GC cases treated with neoadjuvant chemotherapy were downloaded from two medical centers between January 2014 and December 2020, and analyzed by logistic regression and the least absolute shrinkage and selection operator (LASSO) for identifying potential factors that predicted NACT response and might be incorporated in constructing the prediction nomogram. RESULTS: After the inclusion and exclusion criteria were applied, totally 460 cases were enrolled, among which, 307 were males (66.74%) whereas 153 were females (33.26%), with the age of 24-77 (average, 59.37 ± 10.60) years. Consistent with RECIST standard, 242 patients were classified into effective group (PR or CR) while 218 were into ineffective group (PD or SD), with the effective rate of 52.61%. In training set, LASSO and logistic regression analysis showed that five risk factors were significantly associated with NACT effectiveness, including tumor location, Smoking history, T and N stages, and differentiation. In terms of our prediction model, its C-index was 0.842. Moreover, calibration curve showed that the model-predicted results were in good consistence with actual results. Validation based on internal and external validation sets exhibited consistency between training set results and ours. CONCLUSIONS: This study identified five risk factors which were significantly associated with NACT response, including smoking history, clinical T stage, clinical N stage, tumor location and differentiation. The prediction model that exhibited satisfying ability to predict NACT effectiveness was constructed, which may be adopted for identifying the best therapeutic strategy for advanced GC by gastrointestinal surgeons.

RASSF1A inhibits epithelial-mesenchymal transition of gastric cancer cells by downregulating P-JNK.

Gastric cancer (GC) is one of the most common gastrointestinal tumors. In this study, we assessed the biological role of Ras association domain family 1 isoform A (RASSF1A) in GC cells. Expressions of RASSF1A and the relationship of RASSF1A with epithelial-mesenchymal transformation (EMT)-related proteins were assessed in five cell lines using Western blot. GC cells with RASSF1A overexpression were used to study sensitivity to cisplatin, migration, invasion, and the expression of EMT-associated biomarkers. GC cells showed profound downregulation of RASSF1A expression compared with normal human gastric mucosal cells. High RASSF1A expression was associated with increased overall survival. Overexpression of RASSF1A regulates GC cells activity and the expression of EMT-associated biomarkers. RASSF1A regulates E-cadherin and Vimentin through P-JNK pathway. Our results revealed that RASSF1A can inhibit the proliferation, migration, and invasion of GC cells via E-cadherin. Our study provides insights for further research on GC.

Circ_0005758 impedes gastric cancer progression through miR-1229-3p/GCNT4 feedback loop.

Circular RNAs (circRNAs) have been reported to have roles in the carcinogenesis of gastric cancer (GC). Circ_0005758 was discovered to be decreased in GC, here, the detailed functions and molecular mechanism of circ_0005758 in GC progression were investigated. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to measure the levels of genes and proteins. The biological functions of circ_0005758 on GC progression were investigated by using in vitro assays, including 5-ethynyl-2'-deoxyuridine (EDU), transwell, tube formation and flow cytometry, and in vivo murine xenograft model. The binding between miR-1229-3p and circ_0005758 or GCNT4 (Glucosaminyl (N-Acetyl) Transferase 4) was confirmed using dual-luciferase reporter assay and pull-down assay. Circ_0005758 expression was decreased in GC tissues and cells, re-expression of circ_0005758 induced apoptosis and suppressed proliferation, migration, invasion and angiogenesis in GC cells in vitro, and impeded xenograft tumor growth in nude mice. Mechanistically, circ_0005758 sequestered miR-1229-3p to release GCNT4 expression, indicating the circ_0005758/miR-1229-3p/GCNT4 competing endogenous RNA (ceRNA) network GC cells. Besides, an increased miR-1229-3p level and a decreased GCNT4 expression were observed in GC. Rescue experiments demonstrated that miR-1229-3p up-regulation or GCNT4 down-regulation attenuated the anticancer effects of circ_0005758 re-expression on GC cells. Circ_0005758 acts as a tumor suppressor to impede gastric cancer progression via miR-1229-3p/GCNT4 axis, implying that therapeutic targeting of circ_0005758 may better to prevent gastric cancer.

Identification of MATN3 as a Novel Prognostic Biomarker for Gastric Cancer through Comprehensive TCGA and GEO Data Mining.

Gastric cancer (GC) is still a vital malignant cancer across the world with unsatisfactory prognostic results. Matrilin-3 (MATN3) is a member of the extracellular matrix (ECM) protein family. The present research intends to explore the expression level of MATN3 in patients with GC and to explore the prognosis significance of MATN3. In this study, we observed that the MATN3 expression was remarkably upregulated in GC samples in contrast to noncancer samples. Clinical analyses unveiled that high MATN3 expression was related to age, tumor status, and clinical stages. Survival analyses unveiled that patients with high MATN3 expression displayed a poorer overall survival and progression-free survival than those with low MATN3 expression. The AUC of the relevant ROC curve for 1 year, 3 years, and 5 years of survival is 0.571, 0.596, and 0.720, separately. Multivariate assays revealed that MATN3 expression and stage were independent predictors of poor prognosis of GC patients. A meta-analysis unveiled that high MATN3 expression was tightly associated with better overall survival. Overall, our data indicated that MATN3 may have a diagnostic and prognostic value for patients with advanced gastric cancer and assist to improve clinical outcomes for GC patients.

RASSF1A: A promising target for the diagnosis and treatment of cancer.

The Ras association domain family 1 isoform A (RASSF1A), a tumor suppressor, regulates several tumor-related signaling pathways and interferes with diverse cellular processes. RASSF1A is frequently demonstrated to be inactivated by hypermethylation in numerous types of solid cancers. It is also associated with lymph node metastasis, vascular invasion, and chemo-resistance. Therefore, reactivation of RASSF1A may be a viable strategy to block tumor progress and reverse drug resistance. In this review, we have summarized the clinical value of RASSF1A for screening, staging, and therapeutic management of human malignancies. We also highlighted the potential mechanism of RASSF1A in chemo-resistance, which may help identify novel drugs in the future.

Inhibition of epithelial­mesenchymal transition in gastric cancer cells by miR­711­mediated downregulation of CD44 expression.

Gastric cancer is a common malignancy worldwide. The prognosis of early stage gastric cancer patients has significantly improved in recent years. However, in progressive stage gastric cancer patients, the prognosis remains relatively poor due to tumor metastases. In our previous study, we showed that the expression of miR­711 in gastric cancer tissues is low, and restoration of miR­711 inhibited the invasion and migration and the occurrence of epithelial­mesenchymal transition (EMT) in gastric cancer cells. Yet, the mechanisms involved in these processes remain unknown. In the present study, we demonstrated that miR­711­mediated downregulation of CD44 expression inhibited EMT of gastric cancer cells in vitro and in vivo by downregulating vimentin protein expression and upregulating E­cadherin protein expression through transfection, qRT­PCR and western blotting. Therefore, miR­711 may provide a promising target for EMT­related therapy for gastric cancer.

Bioinformatic analysis suggests that UGT2B15 activates the Hippo­YAP signaling pathway leading to the pathogenesis of gastric cancer.

Gastric cancer (GC) is one of the most common malignancies that threatens human health. As the molecular mechanisms unerlying GC are not completely understood, identification of genes related to GC could provide new insights into gene function as well as potential treatment targets. We discovered that UGT2B15 may contribute to the pathogenesis and progression of GC using GEO data and bioinformatic analysis. Using TCGA data, UGT2B15 mRNA was found to be significantly overexpressed in GC tissues; patients with higher UGT2B15 had a poorer prognosis. It was further discovered that UGT2B15 and FOXA1 were both upregulated, and UGT2B15 and Foxa1 were positively correlated in GC. It is known that Foxa1 is a vital threshold to activate the Hippo­YAP signaling pathway. In addition, we suggest that a potential molecular mechanisms includes UGT2B15 which may upregulate Foxa1, activate the Hippo­YAP signaling pathway and contribute to the development of GC. Taken together, our findings demonstrate that UGT2B15 may be an oncogene in GC and is a promising therapeutic target for cancer treatment.