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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.
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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.
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Biomarcadores Tumorais , Neoplasias Gástricas , Humanos , Antígeno Carcinoembrionário , Prognóstico , Antígeno CA-19-9 , Neoplasias Gástricas/patologia , Estudos RetrospectivosRESUMO
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.
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Fenantrenos , Neoplasias Gástricas , Trifluridina , Humanos , Linhagem Celular Tumoral , Animais , Camundongos , Xenoenxertos , Transplante de Neoplasias , Trifluridina/administração & dosagem , Trifluridina/farmacologia , Fenantrenos/administração & dosagem , Fenantrenos/farmacologia , Proliferação de Células/efeitos dos fármacos , Camundongos Nus , Sinergismo Farmacológico , Apoptose/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Neoplasias Gástricas/tratamento farmacológicoRESUMO
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.
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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.
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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.
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Background: We aimed to investigate the association between the number of examined lymph nodes (ELNs) and accurate nodal staging and long-term survival in Siewert type II-III Adenocarcinoma of the Esophagogastric Junction (AEG) by using large population-based databases and determined the optimal ELN number threshold. Methods: Data on Stage I-III Siewert type II-III AEG patients from 2010 to 2014 respectively from the United States (US) SEER database and a Chinese large medical center institutional registry were analyzed for correlation between the ELN number and stage migration (node negative-to-positive) and overall survival (OS) by using multivariable-adjusted logistic and Cox regression models, respectively. The series of odds ratios (ORs), and hazard ratios (HRs) were fitted with a LOWESS smoother, and the structural breakpoints were determined by Chow test. The selected optimal cut point was then validated with the 2015 to 2016 SEER database. Results: Both the US cohort(n=1387) and China cohort(n=981) showed significantly increases from node-negative to node-positive disease (ORtheUS1.032,95%CI 1.017-1.046;ORChina1.034,95%CI 1.002-1.065) and enhancements in overall survival (HRtheUS0.970,95%CI 0.961-0.979;HRChina0.960,95%CI 0.940-0.980) with the increasing ELN number after controlling for confounders. Associations for both stage migration and overall survival were still significant in most subgroups' stratification. Cut point analysis showed a threshold ELN number of 18, which was validated both in the cohorts where it originated and in an independent SEER data cohort(n=379). Conclusions: More ELNs are associated with accurate nodal staging(negative-to-positive) as well as higher overall survival in resected Siewert types II-III AEG, We recommend 18 ELNs as the optimal cut point for the quality assessment of postoperative lymph node examination or prognostic stratification in clinical practice.
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Background: The risk factors of lymph node metastasis (LNM) in gastric cancer (GC) remain controversial. We aimed to identify risk factors of LNM in GC and construct a predictive model. Methods: A total of 1,337 resectable GC patients who underwent radical D2 lymphadenectomy at the first affiliated Hospital of Anhui Medical University from January 2011 to January 2014 were retrospectively analyzed and randomly divided into training and validation cohorts (n = 1,003 and n = 334, respectively) in a 3:1 ratio. Collecting indicators include age, gender, body mass index (BMI), tumor location, pathology, histological grade, tumor size, preoperative neutrophils to lymphocytes ratio (NLR), platelets to lymphocytes ratio (PLR), fibrinogen to albumin ratio (FAR), carcinoembryonic antigen (CEA), cancer antigen19-9 (CA19-9) and lymph nodes status. Significant risk factors were identified through univariate and multivariate logistic regression analysis, which were then included and presented as a nomogram. The performance of the model was assessed with receiver operating characteristic curves (ROC curves), calibration plots, and Decision curve analysis (DCA), and the risk groups were divided into low-and high-risk groups according to the cutoff value which was determined by the ROC curve. Results: BMI, histological grade, tumor size, CEA, and CA19-9 were enrolled in the model as independent risk factors of LNM. The model showed good resolution, with a C-index of 0.716 and 0.727 in the training and validation cohort, respectively, and good calibration. The cutoff value for predicted probability is 0.594, the proportion of patients with LNM in the high-risk group was significantly higher than that in the low-risk group. Decision curve analysis also indicated that the model had a good positive net gain. Conclusions: The nomogram-based prediction model developed in this study is stable with good resolution, reliability, and net gain. It can be used by clinicians to assess preoperative lymph node metastasis and risk stratification to develop individualized treatment plans.
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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.
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Currently, the postoperative prognosis of early stage gastric cancer (GC) is difficult to accurately predict. In particular, social factors are not frequently used in the prognostic assessment of early stage GC. Therefore, this study aimed to combine the clinical indicators and social factors to establish a predictive model for early stage GC based on a new scoring system. A total of 3647 patients with early stage GC from the Surveillance, Epidemiology, and End Results database were included in this study. A Kaplan-Meier survival analysis was used to compare differences in prognosis between different marital status, as an innovative prognostic indicator. Univariate and multivariate analyses were used to screen available prediction factors and then build a nomogram using the Cox proportional hazard regression model. The univariate analysis and multivariate analysis revealed that age at diagnosis, sex, histology, stage_T, surgery, tumor size, and marital status were independent prognostic factors of overall survival. Both the C-index and calibration curves confirmed that the nomogram had a great predictive effect on patient prognosis in training and testing sets. This nomogram based on clinical indicators and marital status can effectively help patients with early stage GC in the future.
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Neoplasias Gástricas , Humanos , Estado Civil , Nomogramas , Prognóstico , Programa de SEER , Neoplasias Gástricas/epidemiologiaRESUMO
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.
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BACKGROUND: The prognosis of patients with hepatocellular carcinoma (HCC) remains difficult to accurately predict. The purpose of this study was to establish a prognostic model for HCC based on a novel scoring system. METHODS: Five hundred and sixty patients who underwent a curative hepatectomy for treatment of HCC at our hospital between January 2007 and January 2014 were included in this study. Univariate and multivariate analyses were used to screen for prognostic risk factors. The nomogram construction was based on Cox proportional hazard regression models, and the development of the new scoring model was analyzed using receiver operating characteristic (ROC) curve analysis and then compared with other clinical indexes. The novel scoring system was then validated with an external dataset from a different medical institution. RESULTS: Multivariate analysis showed that tumor size, portal vein tumor thrombus (PVTT), invasion of adjacent tissues, microvascular invasion, and levels of fibrinogen and total bilirubin were independent prognostic factors. The new scoring model had higher area under the curve (AUC) values compared to other systems, and the C-index of the nomogram was highly consistent for evaluating the survival of HCC patients in the validation and training datasets, as well as the external validation dataset. CONCLUSIONS: Based on serum markers and other clinical indicators, a precise model to predict the prognosis of patients with HCC was developed. This novel scoring system can be an effective tool for both surgeons and patients.
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Gastric cancer (GC) is one of malignant tumors with high mortality and morbidity in the world. MicroRNA-122 (miR-122) acts as a tumor suppressor in a variety of cancers and has been found to be dominant in gastric adenocarcinoma. However, the specific biological function of miR-122-5p in GC is not completely clear. In this study, we found that miR-122-5p was low-expressed in GC tissues and cell lines by using qRT-PCR. Overexpression of miR-122-5p inhibited the proliferation, migration, and invasion of GC cells by using CCK-8 and transwell assays. On the contrary, downregulation of miR-122-5p promoted the proliferation, migration, and invasion of GC cells. In addition, we found that the expression of LYN, an Src family tyrosine kinase, was inversely correlated with miR-122-5p expression in GC tissues by using western blot analysis, immunohistochemistry, and qRT-PCR assays. Meanwhile, luciferase assay results indicated that LYN is a direct target of miR-122-5p in GC cells. Moreover, silencing LYN expression by its siRNA inhibited the proliferation, migration, and invasion of GC cells. Importantly, overexpression of LYN restored miR-122-5p-mediated inhibition of the proliferation, migration, and invasion of GC cells. Taken together, our results indicated miR-122-5p inhibited the proliferation, migration, and invasion by targeting LYN in GC.
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Movimento Celular/genética , Proliferação de Células/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , Neoplasias Gástricas/metabolismo , Quinases da Família src/genética , Quinases da Família src/metabolismo , Regiões 3' não Traduzidas/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Mimetismo Molecular/genética , Mutação , RNA Interferente Pequeno/genética , Neoplasias Gástricas/patologia , TransfecçãoRESUMO
The protein voltage-gated sodium channel Nav1.5 is highly upregulated in various types of cancer and, in general, promotes cancer cell invasiveness and metastatic progression. A previous study found that Nav1.5 was highly expressed in poorly differentiated oral squamous cell carcinoma (OSCC). However, whether Nav1.5 enhances invasiveness and metastasis of OSCC are still unknown. In this study, we found that Nav1.5 was highly expressed in OSCC cell lines compared with normal oral keratinocyte HOK cell line by using western blot analysis. CCK-8 assay results revealed that downregulation of Nav1.5 expression by its specific siRNA reduced proliferation of OSCC HSC-3 cells. Moreover, transwell assay results showed Nav1.5 knockdown significantly inhibited migration and invasion of HSC-3 cells. Meanwhile, qRT-PCR and western blot analysis results showed that epidermal growth factor (EGF) induced Nav1.5 expression in a time- and dose-dependent manner. In addition, EGF promoted proliferation, migration and invasion of HSC-3 cells. Importantly, the Nav1.5 inhibitor tetrodotoxin significantly inhibited the proliferation of HSC-3 cells and impeded the migration and invasion of HSC-3 cells. Furthermore, it was found that siRNA-mediated knockdown of Nav1.5 also lessened the proliferation of HSC-3 cells and blocked the migration and invasion of HSC-3 cells. Taken together, these results indicate that Nav1.5 is involved in the progression of OSCC and Nav1.5 promotes the proliferation, migration and invasion of OSCC cells.
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Carcinoma de Células Escamosas/genética , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Bucais/genética , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fator de Crescimento Epidérmico/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , Invasividade Neoplásica , Interferência de RNA , Bloqueadores dos Canais de Sódio/farmacologia , Tetrodotoxina/farmacologiaRESUMO
Interleukin-34 (IL-34) is a recently discovered cytokine that promotes tissue macrophage maturation and differentiation. We previously found that 1α,25-Dihydroxyvitamin D3 up-regulated IL-34 expression in SH-SY5Y neural cells. However, whether microRNA regulates IL-34 expression is not completely clear. By using on-line TargetScan and MiRanda software, we found that there was only one conserved microRNA-31 (miR-31) binding site in the 3' untranslated region (3'UTR) of IL-34 mRNA. Intriguingly, using qPCR we demonstrated that miR-31 levels were negatively correlated to IL-34 mRNA levels in different cell lines. By examining the effect of miR-31 on IL-34 3' UTR reporter luciferase activity and on IL-34 mRNA and argonaute RISC catalytic component 2 (AGO2) binding, it was found that miR-31 bound directly to IL-34 3'UTR and regulated the post-transcriptional expression of IL-34 in MGC-803 cells. Moreover, a miR-31 mimic significantly reduced IL-34 expression levels while a miR-31 inhibitor up-regulated IL-34 expression in KYSE-45 and HT-29 cells. Taken together, these results show that miR-31 negatively regulates IL-34 expression by directly binding to the IL-34 3' UTR in vitro.