Blood urea nitrogen to albumin ratio is a novel predictor of fatal outcome for patients with severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is associated with a high death rate and lacks a targeted therapy plan. The ratio of blood urea nitrogen to albumin, known as BAR, is a valuable method for assessing the outlook of various infectious diseases. The objective of this research was to evaluate the effectiveness of BAR in forecasting the outcome of individuals with SFTS. Four hundred and thirty-seven patients with SFTS from two clinical centers were included in this study according to inclusion and exclusion criteria. Clinical characteristics and test parameters of SFTS patients were analyzed between survival and fatal groups. Least absolute shrinkage and selection operator (LASSO) regression and Cox regression suggested that BAR might serve as a standalone prognostic indicator for patients with SFTS in the initial phase (hazard ratio = 18.669, 95% confidence interval [CI]: 8.558-40.725, p < 0.001). And BAR had a better predictive effectiveness in clinical outcomes in patients with SFTS with an AUC of 0.832 (95% CI: 0.788-0.876, p < 0.001), a cutoff value of 0.19, a sensitivity of 0.812, and a specificity of 0.726 compared to C-reactive protein, procalcitonin, and platelet to lymphocyte ratio via receiver operating characteristic curve. KM (Kaplan Meier) curves demonstrated that high level of BAR was associated with poor survival condition in patients with SFTS. Furthermore, the high level of BAR was associated with long hospital stays and test paraments of kidney, liver, and coagulation function in survival patients. So, BAR could be used as a promising early warning biomarker of adverse outcomes in patients with SFTS.

Cholesterol metabolism in tumor microenvironment: cancer hallmarks and therapeutic opportunities.

Cholesterol is crucial for cell survival and growth, and dysregulation of cholesterol homeostasis has been linked to the development of cancer. The tumor microenvironment (TME) facilitates tumor cell survival and growth, and crosstalk between cholesterol metabolism and the TME contributes to tumorigenesis and tumor progression. Targeting cholesterol metabolism has demonstrated significant antitumor effects in preclinical and clinical studies. In this review, we discuss the regulatory mechanisms of cholesterol homeostasis and the impact of its dysregulation on the hallmarks of cancer. We also describe how cholesterol metabolism reprograms the TME across seven specialized microenvironments. Furthermore, we discuss the potential of targeting cholesterol metabolism as a therapeutic strategy for tumors. This approach not only exerts antitumor effects in monotherapy and combination therapy but also mitigates the adverse effects associated with conventional tumor therapy. Finally, we outline the unresolved questions and suggest potential avenues for future investigations on cholesterol metabolism in relation to cancer.

Diagnosis of colorectal cancer based on folate receptor-positive circulating tumor cell analysis: a retrospective cohort study.

BACKGROUND: Early diagnosis and treatment are crucial to improve the prognosis of colorectal cancer (CRC). At present, there is a lack of an accurate CRC screening factor. We conducted folate receptor-positive circulating tumor cell analysis (FR + CTC analysis) in distinguishing CRC from benign colorectal diseases to evaluate the diagnostic efficiency. METHODS: Clinical data of patients admitted to The First Affiliated Hospital of Anhui Medical University from January 2021 to July 2022 were retrospectively collected. Levels of FR + CTC and other indicators were analyzed. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of these molecular biomarkers. RESULTS: Data of 103 patients with CRC and 54 patients with benign colorectal diseases were collected. FR + CTC levels were observed significantly higher in CRC patients than in patients with benign colorectal diseases (P < 0.001). FR + CTC level was correlated with tumor diameter, differentiation, T-stage, pathological stage, clinical stage, and intravascular tumor thrombus in patients with CRC (P < 0.05). The optimal cutoff value of FR + CTC level for diagnosing CRC patients was 7.66 FU/3 ml, with a sensitivity of 85.4%, a specificity of 74.1%, and an Area Under Curve (AUC) of 0.855 (95% CI 0.77-0.923). In < 50-years old patients with CRC, the diagnostic efficiency of FR + CTC was excellent, with an AUC of 0.936 (95% CI 0.877-0.995). CONCLUSION: FR + CTC counting has excellent diagnostic efficiency in screening of CRC. FR + CTC count can also predict the tumor stage of CRC patients before surgery, and guide the choice of treatment.

Advantage of log odds of positive lymph nodes in prognostic evaluation of patients with early-onset colon cancer.

BACKGROUND: Colon cancer (CC) is one of the most common cancers of the digestive tract, the third most common cancer worldwide, and the second most common cause of cancer-related deaths. Previous studies have demonstrated a higher risk of lymph node metastasis (LNM) in young patients with CC. It might be reasonable to treat patients with early-onset locally advanced CC with extended lymph node dissection. However, few studies have focused on early-onset CC (ECC) patients with LNM. At present, the methods of predicting and evaluating the prognosis of ECC patients with LNM are controversial. AIM: To compare the prognostic values of four lymph node staging indices and establish the best nomogram for patients with ECC. METHODS: From the data of patients with CC obtained from the Surveillance, Epidemiology, and End Results (SEER) database, data of young patients with ECC (≤ 50 years old) was screened. Patients with unknown data were excluded from the study, while the remaining patients were included. The patients were randomly divided into a training group (train) and a testing group (test) in the ratio of 7:3, while building the model. The model was constructed by the training group and verified by the testing group. Using multiple Cox regression models to compare the prediction efficiency of LNM indicators, nomograms were built based on the best model selected for overall survival (OS) and cause-specific survival (CSS). In the two groups, the performance of the nomogram was evaluated by constructing a calibration plot, time-dependent area under the curve (AUC), and decision curve analysis. Finally, the patients were grouped based on the risk score predicted by the prognosis model, and the survival curve was constructed after comparing the survival status of the high and low-risk groups. RESULTS: Records of 26922 ECC patients were screened from the SEER database. N classification, positive lymph nodes (PLN), lymph node ratio (LNR) and log odds of PLN (LODDS) were considered to be independent predictors of OS and CSS. In addition, independent risk factors for OS included gender, race, marital status, primary site, histology, grade, T, and M classification, while the independent prognostic factors for CSS included race, marital status, primary site, grade, T, and M classification. The prediction model including LODDS is composed of minimal Akaike information criterion, maximal concordance indexes, and AUCs. Factors including gender, race, marital status, primary site, histology, grade, T, M classification, and LODDS were integrated into the OS nomogram, while race, marital status, primary site, grade, T, M classification, and LODDS were included into the CSS nomogram. The nomogram representing both cohorts had been successfully verified in terms of prediction accuracy and clinical practicability. CONCLUSION: LODDS is superior to N-stage, PLN, and LNR of ECC. The nomogram containing LODDS might be helpful in tumor evaluation and clinical decision-making, since it provides an appropriate prediction of ECC.

Correction to "Interleukin-34 promotes the proliferation and epithelial-mesenchymal transition of gastric cancer cells".

[This corrects the article on p. 1968 in vol. 14, PMID: 36310707.].

Prediction of overall survival after radical gastrectomy using nomograms created by tumor markers.

Prediction of prognosis after radical resection of gastric cancer has not been well established. Therefore, we aimed to establish a prognostic model based on a new score system of patients with gastric cancer. A total of 1235 patients who underwent curative gastrectomy at our hospital from October 2015 to April 2017 were included in this study. Univariate and multivariate analyses were used to screen for prognostic risk factors. Construction of the nomogram was based on Cox proportional hazard regression models. The construction of the new score models was analyzed by the receiver operating characteristic curve (ROC curve), calibration curve, and decision curve. Multivariate analysis showed that tumor size, T, N, carcinoembryonic antigen, CA125, and CA19-9 were independent prognostic factors. The new score model had a greater AUC (The area under the ROC curve) than other systems, and the C-index of the nomogram was highly reliable for evaluating the survival of patients with gastric cancer. Based on the tumor markers and other clinical indicators, we developed a precise model to predict the prognosis of patients with gastric cancer after radical surgery. This score system can be helpful to both surgeons and patients.

Prognostic significance of post-preoperative tumor markers increments in patients with non-metastatic gastric cancer.

PURPOSE: Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are the most common tumor markers detected before and after gastric cancer (GC) surgery. However, the impact of post-preoperative CEA/CA19-9 increments on prognosis of GC remains unclear. In addition, there is no research incorporating post-preoperative CEA/CA19-9 increments into the prognostic model. METHODS: Patients who underwent radical gastrectomy for GC at the First Affiliated Hospital of Anhui Medical University and Anhui Provincial Hospital from January 2013 to December 2017 were enrolled and divided into the discovery and validation cohort. Prognostic value of post-preoperative CEA/CA19-9 increments and preoperative CEA/CA199 levels were assessed by Kaplan-Meier log-rank analysis and compared by time-dependent receiver operating characteristic (t-ROC) curves. Multivariate Cox regression analysis was applied to establish the nomogram. The performance of the prognostic model was validated by the concordance index (C-index), calibration curve, and ROC curve analysis. RESULTS: A total of 562 GC patients were included in this study. Overall survival (OS) rates decreased with an increasing number of incremental tumor markers after surgery. The t-ROC curves implied that the prognostic ability of the number of incremental post-preoperative tumor markers was superior to that of the number of positive preoperative tumor markers. Cox regression analysis suggested that the number of incremental post-preoperative tumor markers was an independent prognostic factor. The nomogram incorporated with the post-preoperative CEA/CA19-9 increments showed reliable accuracy. CONCLUSIONS: Incremental post-preoperative CEA/CA19-9 were indicator of poor prognosis of GC. The prognostic value of post-preoperative CEA/CA19-9 increments exceed that of preoperative CEA/CA19-9 levels.

Effects and mechanisms of trifluridine alone or in combination with cryptotanshinone in inhibiting malignant biological behavior of gastric cancer.

BACKGROUND: The incidence of gastric cancer (GC) ranks fourth among all malignant tumors worldwide, and the fatality rate ranks second among all malignant tumors. Several Chinese traditional medicines have been used in the treatment of advanced gastric cancer. This study aims to investigate the effect of combinational use of natural product cryptotanshinone (CTS) with anti-cancer drug trifluorothymidine (FTD) in GC. METHODS: Cell Counting Kit-8 assay was used to detect the inhibitory effect of the combinational or separate use of FTD and CTS on the growth of HGC-27 and AGS GC cells. The combined index of FTD and CTS was calculated using CompuSyn software. To understand the mechanism, we applied flow cytometry to study the cell cycle and cell apoptosis after treatment. We also investigated the amount of FTD incorporated into the DNA by immunofluorescence assay. The expression of relevant proteins was monitored using western blot. Furthermore, the effect of using TAS-102 in combination with CTS was studied in xenograft tumor nude mice model. RESULTS: FTD and CTS inhibited the growth of GC cells in a dose-dependent manner, respectively. They both exhibited low to sub-micromolar potency in HGC-27 and AGS cells. The combination of FTD and CTS showed synergistic anticancer effect in HGC-27 cells and AGS cells. Our mechanism studies indicate that FTD could block HGC-27 cells at G2/M phase, while CTS could block HGC-27 cells at G1/G0 phase, while FTD combined with CTS could mainly block HGC-27 cells at G2 phase. FTD in combination with CTS significantly increased the apoptosis of HGC-27 cells. We observed that CTS treatment increased the incorporation of FTD into the DNA HGC-27 cell. FTD treatment activated STAT3 phosphorylation in HGC-27 cells, while CTS treatment down-regulated the concentration of p-STAT3. Interestingly, the combination of CTS and FTD reduced STAT3 phosphorylation induced by FTD. In the in vivo experiments, we observed that the combination of TAS-102 with CTS was significantly more potent than TAS-102 on tumor growth inhibition. CONCLUSIONS: FTD combined with CTS has a synergistic anti-gastric cancer effect as shown by in vitro and in vivo experiments, and the combined treatment of FTD and CTS will be a promising treatment option for advanced gastric cancer.

Nomogram established using risk factors of early gastric cancer for predicting the lymph node metastasis.

BACKGROUND: For the prognosis of patients with early gastric cancer (EGC), lymph node metastasis (LNM) plays a crucial role. A thorough and precise evaluation of the patient for LNM is now required. AIM: To determine the factors influencing LNM and to construct a prediction model of LNM for EGC patients. METHODS: Clinical information and pathology data of 2217 EGC patients downloaded from the Surveillance, Epidemiology, and End Results database were collected and analyzed. Based on a 7:3 ratio, 1550 people were categorized into training sets and 667 people were assigned to testing sets, randomly. Based on the factors influencing LNM determined by the training sets, the nomogram was drawn and verified. RESULTS: Based on multivariate analysis, age at diagnosis, histology type, grade, T-stage, and size were risk factors of LNM for EGC. Besides, nomogram was drawn to predict the risk of LNM for EGC patients. Among the categorical variables, the effect of grade (well, moderate, and poor) was the most significant prognosis factor. For training sets and testing sets, respectively, area under the receiver-operating characteristic curve of nomograms were 0.751 [95% confidence interval (CI): 0.721-0.782] and 0.786 (95%CI: 0.742-0.830). In addition, the calibration curves showed that the prediction model of LNM had good consistency. CONCLUSION: Age at diagnosis, histology type, grade, T-stage, and tumor size were independent variables for LNM in EGC. Based on the above risk factors, prediction model may offer some guiding implications for the choice of subsequent therapeutic approaches for EGC.

Efficacy and outcome of extensive intraoperative peritoneal lavage plus surgery vs surgery alone with advanced gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors. After resection, one of the major problems is its peritoneal dissemination and recurrence. Some free cancer cells may still exist after resection. In addition, the surgery itself may lead to the dissemination of tumor cells. Therefore, it is necessary to remove residual tumor cells. Recently, some researchers found that extensive intraoperative peritoneal lavage (EIPL) plus intraperitoneal chemotherapy can improve the prognosis of patients and eradicate peritoneal free cancer for GC patients. However, few studies explored the safety and long-term outcome of EIPL after curative gastrectomy. AIM: To evaluate the efficacy and long-term outcome of advanced GC patients treated with EIPL. METHODS: According to the inclusion and exclusion criteria, a total of 150 patients with advanced GC were enrolled in this study. The patients were randomly allocated to two groups. All patients received laparotomy. For the non-EIPL group, peritoneal lavage was washed using no more than 3 L of warm saline. In the EIPL group, patients received 10 L or more of saline (1 L at a time) before the closure of the abdomen. The surviving rate analysis was compared by the Kaplan-Meier method. The prognostic factors were carried out using the Cox appropriate hazard pattern. RESULTS: The basic information in the EIPL group and the non-EIPL group had no significant difference. The median follow-up time was 30 mo (range: 0-45 mo). The 1- and 3-year overall survival (OS) rates were 71.0% and 26.5%, respectively. The symptoms of ileus and abdominal abscess appeared more frequently in the non-EIPL group (P < 0.05). For the OS of patients, the EIPL, Borrmann classification, tumor size, N stage, T stage and vascular invasion were significant indicators. Then multivariate analysis revealed that EIPL, tumor size, vascular invasion, N stage and T stage were independent prognostic factors. The prognosis of the EIPL group was better than the non-EIPL group (P < 0.001). The 3-year survival rate of the EIPL group (38.4%) was higher than the non-EIPL group (21.7%). For the recurrence-free survival (RFS) of patients, the risk factor of RFS included EIPL, N stage, vascular invasion, type of surgery, tumor location, Borrmann classification, and tumor size. EIPL and tumor size were independent risk factors. The RFS curve of the EIPL group was better than the non-EIPL group (P = 0.004), and the recurrence rate of the EIPL group (24.7%) was lower than the non-EIPL group (46.4%). The overall recurrence rate and peritoneum recurrence rate in the EIPL group was lower than the non-EIPL group (P < 0.05). CONCLUSION: EIPL can reduce the possibility of perioperative complications including ileus and abdominal abscess. In addition, the overall survival curve and RFS curve were better in the EIPL group.

F-box and leucine-rich repeat 6 promotes gastric cancer progression via the promotion of epithelial-mesenchymal transition.

BACKGROUND: F-box and leucine-rich repeat 6 (FBXL6) have reportedly been associated with several cancer types. However, the role and mechanisms of FBXL6 in gastric cancer (GC) require further elucidation. AIM: To investigate the effect of FBXL6 in GC tissues and cells and the underlying mechanisms. METHODS: TCGA and GEO database analysis was performed to evaluate the expression of FBXL6 in GC tissues and adjacent normal tissues. Reverse transcription-quantitative polymerase chain reaction, immunofluorescence, and western blotting were used to detect the expression of FBXL6 in GC tissue and cell lines. Cell clone formation, 5-ethynyl-2'-deoxyuridine (EdU) assays, CCK-8, transwell migration assay, and wound healing assays were performed to evaluate the malignant biological behavior in GC cell lines after transfection with FBXL6-shRNA and the overexpression of FBXL6 plasmids. Furthermore, in vivo tumor assays were performed to prove whether FBXL6 promoted cell proliferation in vivo. RESULTS: FBXL6 expression was upregulated more in tumor tissues than in adjacent normal tissues and positively associated with clinicopathological characteristics. The outcomes of CCK-8, clone formation, and Edu assays demonstrated that FBXL6 knockdown inhibited cell proliferation, whereas upregulation of FBXL6 promoted proliferation in GC cells. Additionally, the transwell migration assay revealed that FBXL6 knockdown suppressed migration and invasion, whereas the overexpression of FBXL6 showed the opposite results. Through the subcutaneous tumor implantation assay, it was evident that the knockdown of FBXL6 inhibited GC graft tumor growth in vivo. Western blotting showed that the effects of FBXL6 on the expression of the proteins associated with the epithelial-mesenchymal transition-associated proteins in GC cells. CONCLUSION: Silencing of FBXL6 inactivated the EMT pathway to suppress GC malignancy in vitro. FBXL6 can potentially be used for the diagnosis and targeted therapy of patients with GC.

Development and validation of a novel nomogram for predicting overall survival in gastric cancer based on inflammatory markers.

BACKGROUND: Nearly 66% of occurrences of gastric cancer (GC), which has the second-highest death rate of all cancers, arise in developing countries. In several cancers, the predictive significance of inflammatory markers has been established. AIM: To identify clinical characteristics and develop a specific nomogram to determine overall survival for GC patients. METHODS: Nine hundred and four GC patients treated at the First Affiliated Hospital of Anhui Medical University between January 2010 and January 2013 were recruited. Prognostic risk variables were screened for Cox analysis. The C index, receiver operator characteristic (ROC) curve, and decision curve analysis were used to evaluate the nomogram. RESULTS: Tumor node metastasis stage, carcinoembryonic antigen, systemic immune-inflammation index, and age were identified as independent predictive variables by multivariate analysis. Systemic immune-inflammation index value was superior to that of other inflammatory indicators. The ROC indicated the nomogram had a higher area under the curve than other factors, and its C-index for assessing the validation and training groups of GC patients was extremely reliable. CONCLUSION: We created a novel nomogram to forecast the prognosis of GC patients following curative gastrectomy based on blood markers and other characteristics. Both surgeons and patients can benefit significantly from this new scoring system.

Interleukin-34 promotes the proliferation and epithelial-mesenchymal transition of gastric cancer cells.

BACKGROUND: Interleukin (IL)-34 is a pro-inflammatory cytokine involved in tumor development. The role of IL-34 in the proliferation and epithelial-mesenchymal transition (EMT) of gastric cancer (GC) remains to be investigated. AIM: To investigate whether and how IL-34 affects the proliferation of GC cells and EMT. METHODS: Using immunohistochemical staining, the expression of IL-34 protein was detected in 60 paired GC and normal paracancerous tissues and the relationship between IL-34 and clinicopathological factors was analyzed. The expression of IL-34 mRNA and protein in normal gastric epithelial cell lines and GC was detected using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. Stable IL-34 knockdown and overexpression in AGS cell lines were established by lentiviral infection and validated by qRT-PCR and western blotting. The cholecystokinin-8 assay, clone formation assay, cell scratch assay, and transwell system were used to detect GC cell proliferation, clone formation, migration, and invasion capacity, respectively. The effects of IL-34 on the growth of GC transplant tumors were assessed using a subcutaneous transplant tumor assay in nude mice. The effects of IL-34 on the expression level of EMT-associated proteins in AGS cells were examined by western blotting. RESULTS: Expression of IL-34 protein and mRNA was higher in GC cell lines than in GES-1 cells. Compared to matched normal paraneoplastic tissues, the expression of IL-34 protein was higher in 60 GC tissues, which was correlated with tumor size, T-stage, N-stage, tumor, node and metastasis stage, and degree of differentiation. Knockdown of IL-34 expression inhibited the proliferation, clone formation, migration, and invasion of AGS cells, while overexpression of IL-34 promoted cell proliferation, clone formation, migration, and invasion. Furthermore, the reduction of IL-34 promoted the expression of E-cadherin in AGS cells but inhibited the expression of vimentin and N-cadherin. Overexpression of IL-34 inhibited E-cadherin expression but promoted expression of vimentin and N-cadherin in AGS cells. Overexpression of IL-34 promoted the growth of subcutaneous transplanted tumors in nude mice. CONCLUSION: IL-34 expression is increased in GC tissues and cell lines compared to normal gastric tissues or cell lines. In GC cells, IL-34 promoted proliferation, clone formation, migration, and invasion by regulating EMT-related protein expression cells. Interference with IL-34 may represent a novel strategy for diagnosis and targeted therapy of GC.

Model established based on blood markers predicts overall survival in patients after radical resection of types II and III adenocarcinoma of the esophagogastric junction.

BACKGROUND: In recent years, the incidence of types II and III adenocarcinoma of the esophagogastric junction (AEG) has shown an obvious upward trend worldwide. The prognostic prediction after radical resection of AEG has not been well established. AIM: To establish a prognostic model for AEG (types II and III) based on routine markers. METHODS: A total of 355 patients who underwent curative AEG at The First Affiliated Hospital of Anhui Medical University from January 2014 to June 2015 were retrospectively included in this study. Univariate and multivariate analyses were performed to identify the independent risk factors. A nomogram was constructed based on Cox proportional hazards models. The new score models was analyzed by C index and calibration curves. The receiver operating characteristic (ROC) curve was used to compare the predictive accuracy of the scoring system and tumor-node-metastasis (TNM) stage. Overall survival was calculated using the Kaplan-Meier curve amongst different risk AEG patients. RESULTS: Multivariate analysis showed that TNM stage (hazard ratio [HR] = 2.286, P = 0.008), neutrophil-to-lymphocyte ratio (HR = 2.979, P = 0.001), and body mass index (HR = 0.626, P = 0.026) were independent prognostic factors. The new scoring system had a higher concordance index (0.697), and the calibration curves of the nomogram were reliable. The area under the ROC curve of the new score model (3-year: 0.725, 95% confidence interval [CI]: 0.676-0.777; 5-year: 0.758, 95%CI: 0.708-0.807) was larger than that of TNM staging (3-year: 0.630, 95%CI: 0.585-0.684; 5-year: 0.665, 95%CI: 0.616-0.715). CONCLUSION: Based on the serum markers and other clinical indicators, we have developed a precise model to predict the prognosis of patients with AEG (types II and III). The new prognostic nomogram could effectively enhance the predictive value of the TNM staging system. This scoring system can be advantageous and helpful for surgeons and patients.

Prognostic factors for disease-free survival in postoperative patients with hepatocellular carcinoma and construction of a nomogram model.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and has a high risk of invasion and metastasis along with a poor prognosis. AIM: To investigate the independent predictive markers for disease-free survival (DFS) in patients with HCC and establish a trustworthy nomogram. METHODS: In this study, 445 patients who were hospitalized in The First Affiliated Hospital of Anhui Medical College between December 2009 and December 2014 were retrospectively examined. The survival curve was plotted using the Kaplan-Meier method and survival was determined using the log-rank test. To identify the prognostic variables, multivariate Cox regression analyses were carried out. To predict the DFS in patients with HCC, a nomogram was created. C-indices and receiver operator characteristic curves were used to evaluate the nomogram's performance. Decision curve analysis (DCA) was used to evaluate the clinical application value of the nomogram. RESULTS: Longer DFS was observed in patients with the following characteristics: elderly, I-II stage, and no history of hepatitis B. The calibration curve showed that this nomogram was reliable and had a higher area under the curve value than the tumor node metastasis (TNM) stage. Moreover, the DCA curve revealed that the nomogram had good clinical applicability in predicting 3- and 5-year DFS in HCC patients after surgery. CONCLUSION: Age, TNM stage, and history of hepatitis B infection were independent factors for DFS in HCC patients, and a novel nomogram for DFS of HCC patients was created and validated.

Cryptotanshinone inhibits cytotoxin-associated gene A-associated development of gastric cancer and mucosal erosions.

BACKGROUND: Approximately 90% of new cases of noncardiac gastric cancer (GC) are related to Helicobacter pylori (H. pylori), and cytotoxin-associated gene A (CagA) is one of the main pathogenic factors. Recent studies have shown that the pharmacological effects of cryptotanshinone (CTS) can be used to treat a variety of tumors. However, the effects of CTS on H. pylori, especially CagA+ strain-induced gastric mucosal lesions, on the development of GC is unknown. AIM: To assess the role of CTS in CagA-induced proliferation and metastasis of GC cells, and determine if CagA+ H. pylori strains causes pathological changes in the gastric mucosa of mice. METHODS: The effects of CTS on the proliferation of GC cells were assessed using the Cell Counting Kit-8 (CCK-8) assay, and the abnormal growth, migration and invasion caused by CagA were detected by CCK-8 and transwell assays. After transfection with pSR-HA-CagA and treatment with CTS, proliferation and metastasis were evaluated by CCK-8 and transwell assays, respectively, and the expression of Src homology 2 (SH2) domain-containing phosphatase 2 (SHP2) and phosphorylated SHP2 (p-SHP2) was detected using western blotting in AGS cells. The enzyme-linked immunosorbent assay was used to determine the immunoglobulin G (IgG) level against CagA in patient serum. Mice were divided into four groups and administered H. pylori strains (CagA+ or CagA-) and CTS (or PBS) intragastrically, and establishment of the chronic infection model was verified using polymerase chain reaction and sequencing of isolated strains. Hematoxylin and eosin staining was used to assess mucosal erosion in the stomach and toxicity to the liver and kidney. RESULTS: CTS inhibited the growth of GC cells in dose- and time-dependent manners. Overexpression of CagA promoted the growth, migration, and invasion of GC cells. Importantly, we demonstrated that CTS significantly inhibited the CagA-induced abnormal proliferation, migration, and invasion of GC cells. Moreover, the expression of p-SHP2 protein in tumor tissue was related to the expression of IgG against CagA in the serum of GC patients. Additionally, CTS suppressed the protein expression levels of both SHP2 and p-SHP2 in GC cells. CTS suppressed CagA+ H. pylori strain-induced mucosal erosion in the stomach of mice but had no obvious effects on the CagA- H. pylori strain group. CONCLUSION: CTS inhibited CagA-induced proliferation and the epithelial-mesenchymal transition of GC cells in vitro, and CagA+ H. pylori strains caused mucosal erosions of the stomach in vivo by decreasing the protein expression of SHP2.

Identification of a ferroptosis-related gene signature predictive model in colon cancer.

BACKGROUND: The prognosis of colon cancer (CC) is challenging to predict due to its highly heterogeneous nature. Ferroptosis, an iron-dependent form of cell death, has roles in various cancers; however, the correlation between ferroptosis-related genes (FRGs) and prognosis in CC remains unclear. METHODS: The expression profiles of FRGs and relevant clinical information were retrieved from the Cancer Genome Atlas (TCGA) database. Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression model were performed to build a prognostic model in TCGA cohort. RESULTS: Ten FRGs, five of which had mutation rates ≥ 3%, were found to be related to the overall survival (OS) of patients with CC. Patients were divided into high- and low-risk groups based on the results of Cox regression and LASSO analysis. Patients in the low-risk group had a significantly longer survival time than patients in the high-risk group (P < 0.001). Enrichment analyses in different risk groups showed that the altered genes were associated with the extracellular matrix, fatty acid metabolism, and peroxisome. Age, risk score, T stage, N stage, and M stage were independent predictors of patient OS based on the results of Cox analysis. Finally, a nomogram was constructed to predict 1-, 3-, and 5-year OS of patients with CC based on the above five independent factors. CONCLUSION: A novel FRG model can be used for prognostic prediction in CC and may be helpful for individualized treatment.

Overexpression of GSE1 Related to Trastuzumab Resistance in Gastric Cancer Cells.

Gastric cancer is one of the most prevalent human cancers with poor prognosis. Trastuzumab is a well-used targeted drug for gastric cancer with HER2 amplification. Trastuzumab resistance restrains the clinical use of trastuzumab. In this study, we reported human Gse1 coiled-coil protein (GSE1) promoted trastuzumab resistance in HER2-positive gastric cancer cells. Acquired trastuzumab-resistant gastric cancer cells overexpressed GSE1, and depletion of GSE1 decreased the trastuzumab resistance of trastuzumab-resistant gastric cancer cells. BCL-2 was a downstream gene positively regulated by GSE1 and also performed promoting the role of trastuzumab resistance in HER2-positive gastric cancer cells. A high level of GSE1 was associated with a high risk of tumor lymph node metastasis and higher clinical stage in HER2-positive gastric cancer patients. GSE1 was a potential target that could be used for HER2-positive gastric cancer therapy.

Proteome Analyses Reveal S100A11, S100P, and RBM25 Are Tumor Biomarkers in Colorectal Cancer.

PURPOSE: The prognosis for colorectal cancer (CRC) patients is drastically impacted by the presence of lymph node or liver metastases at diagnosis or resection. On this basis it is sought to identify novel proteins as biomarkers and determinants of CRC metastasis. EXPERIMENTAL DESIGN: Proteomic analyses are undertaken using primary tissues from ten Chinese CRC patients presenting with or without liver metastases and immunohistochemistry used to validate selected proteins in an independent patient cohort. RESULTS: Comparing CRC against paired normal adjacent tissues identifies 1559 differentially expressed proteins (DEPs) with 974 upregulated and 585 downregulated proteins, respectively. The highest number of DEPs is selectively associated with metastatic tumors (519 upregulated and 267 downregulated proteins, respectively) with a smaller number of unique DEPs identified only in non-metastatic CRC cases (116 upregulated and 29 downregulated proteins, respectively). The remaining DEPs are commonly expressed in both non-metastatic and metastatic tumors. The upregulation of three representative DEPs (S100A11, S100P, and RBM25) is confirmed using immunohistochemistry against 154 CRC tissues embedded in a tissue microarray. CONCLUSIONS AND CLINICAL RELEVANCE: The data reveal both previously identified CRC biomarkers along with novel candidates which provide a ready resource of DEPs in CRC for further investigation.