Prognostic Factor In Gastric Cancer Research Articles

A novel TGFbeta/TGILR axis mediates crosstalk between cancer-associated fibroblasts and tumor cells to drive gastric cancer progression

Transforming growth factor beta (TGFβ) signaling plays a critical role in tumorigenesis and metastasis. However, little is known about the biological function of TGFbeta-induced lncRNA in cancer. In this study, we discovered a novel TGFbeta-induced lncRNA, termed TGILR, whose function in cancer remains unknown to date. TGILR expression was directly activated by the canonical TGFbeta/SMAD3 signaling axis, and this activation is highly conserved in cancer. Clinical analysis showed that TGILR overexpression showed a significant correlation with lymph node metastasis and poor survival and was an independent prognostic factor in gastric cancer (GC). Depletion of TGILR caused an obvious inhibitory effect on GC cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) in vitro and in vivo. More importantly, we demonstrated that TGFbeta signaling in GC was overactivated due to cancer-associated fibroblast (CAF) infiltration. Mechanistically, increased level of CAF-secreted TGFbeta activates TGFbeta signaling, leading to TGILR overexpression in GC cells. Meanwhile, TGILR overexpression inhibited the microRNA biogenesis of miR-1306 and miR-33a by interacting with TARBP2 and reducing its protein stability, thereby promoting GC progression via TCF4-mediated EMT signaling. In conclusion, CAF infiltration drives GC metastasis and EMT signaling through activating TGFbeta/TGILR axis. Targeted blocking of CAF-derived TGFbeta should be a promising anticancer strategy in GC.

Stroma AReactive Invasion Front Areas (SARIFA) predict poor survival in adenocarcinomas of the stomach and gastrooesophageal junction: a validation study.

Recently, the presence of "Stroma AReactive Invasion Front Areas" (SARIFA) has been described as a promising adverse prognostic factor in gastric cancer. However, the validity of this approach still needs to be tested. The aim of this study was to independently assess the utility of the proposed method in a well-characterised cohort of primary resected adenocarcinomas of stomach and gastrooesophageal junction (n = 392). SARIFA status was analysed on routine slides of resection specimens. Cases were divided into SARIFA-positive and negative groups and analysed in relation to clinicopathological and survival data. SARIFA positivity was found in 15.1% (n = 59) cases and was significantly associated with Lauren phenotype (p < 0.001), pT (p = 0.001), pN (p = 0.018), UICC stage (p = 0.031), tumour budding (p = 0.002), overall survival (p < 0.001) and cancer-specific survival (p < 0.001). SARIFA-positive tumours had a worse prognosis in the multivariate setting (HR = 1.847, 95% CI: 1.300-2.624, p = 0.001). SARIFA status is an independent prognostic factor in gastric cancer, in particular in locally advanced tumours.

Expressions and Clinical Significance of Met and YAP in Gastric Cancer Tissue Microarray.

This study is aimed at investigating the expression of Met and YAP in gastric cancer and their impact on clinical prognosis. Tissue samples and clinical data were collected from 89 patients with gastric cancer. Immunohistochemistry was performed to quantify the expression of Met and YAP using tissue microarray. The correlation between the expressions of Met, YAP, and clinicopathological characteristics of patients was determined using a chi-square test. Survival analysis was conducted using the Kaplan-Meier method, while multivariate survival analysis was performed using the Cox proportional hazard model. Bioinformatics analysis was carried out by downloading chip data from TCGA. The expression levels of both Met and YAP were significantly higher in gastric cancer tissues compared to adjacent tissues (P < 0.001). Met expression showed a positive association with P53 and CD133, whereas YAP expression correlated positively with tumor grade and CD133 (P < 0.05). Pearson's analysis revealed a significant correlation between Met expression and VEGFR as well as CD133, while YAP expression correlated with Ki67 and VEGFR (P < 0.05). Patients with high levels of both Met and YAP exhibited decreased survival time (P < 0.01). Furthermore, Met expression, N stage, and VEGFR were identified as independent risk factors for gastric cancer prognosis (P < 0.05), whereas no such association was observed for YAP expression. Bioinformatics analysis demonstrated a significant correlation between the expressions of Met and YAP; both proteins were highly expressed in gastric cancer patients accompanied by markedly reduced survival time. The expressions of Met and YAP are closely associated with the survival outcomes as well as clinicopathological features in patients with gastric cancer. Moreover, our findings highlight that Met serves as an independent prognostic factor for gastric cancer.

Gastric Cancer With the Increased Nicotinamide N-methyltransferase-positive Stromal Cells Includes Unfavorable Prognosis-related Cancer-associated Fibroblasts.

"Stromal high expression" of Nicotinamide N-methyltransferase (NNMT), previously reported as a poor prognostic factor of gastric cancer, was based on immunohistochemical H-score. However, this could simply indicate an increase in cancer-associated fibroblasts (CAFs) because NNMT is positive for fibroblasts. To verify this, the proportion and staining intensity of stromal NNMT-positive stellate/spindle cells were evaluated separately and examined for its association with related proteins (H3K4me3, H3K27me3, and LOXL2). Immunohistochemistry for NNMT, H3K4me3, H3K27me3, and LOXL2 was performed on 521 tissue microarrays of gastric cancer. Cancer stromal stellate/spindle cells were evaluated according to morphology, proportion, and stain intensity of NNMT, loss of H3K4me3 and H3K27me3, and stain intensity of LOXL2. Their associations with clinicopathological characteristics and overall survival were examined. Higher staining intensity of NNMT was not related to a poorer prognosis. However, higher proportion of NNMT-positive stellate/spindle cells indirectly contributed to a poor prognosis. It was associated with CAF-like morphology and a global decrease in H3K4me3/H3K27me3, which were both associated with high LOXL2 expression. These three factors were independent poor prognostic factors. In addition, in the LOXL2-high group, prognosis significantly deteriorated with the presence of a global decrease in H3K4me3/H3K27me3. The higher proportion of NNMT-positive cancer stromal cells in gastric cancer serves as an indicator for identifying unfavorable prognostic CAFs that show a global decrease in H3K4me3/H3K27me3. This facilitates research on the nature of these cells and their characteristics.

Abstract 5133: Gastric cancer carrying FAT4 mutations associated with favorable prognosis in comparison to wild-type: Results from Real-World Cohorts

Abstract Introduction: Gastric cancer (GC) is a complex and heterogeneous disease with variable clinical outcomes. Identifying prognostic factors that can reliably predict patient outcomes is crucial for personalized treatment strategies. In this study, we aimed to investigate the impact of mutations in the FAT4 gene as potential prognostic factors in gastric cancer. Methods: We conducted a comprehensive analysis of genomic data from a cohort of 236 gastric cancer patients to identify mutations in the FAT4 gene and validated it using the TCGA cohort. The mutational landscape of FAT4 was analyzed using next-generation sequencing (NGS) techniques. Clinical data, including patient demographics, tumor characteristics, and survival outcomes, were collected and correlated with the presence of FAT4 cadherin mutations. Results: In the real-world cohort, the occurrence of mutations of FAT4 was 19.1% (45/236), while in the TCGA cohort, it was 21.0% (89/423). Specifically, the mutation rates in the single cadherin functional domain of FAT4 were 10.2% (24/236) in the real-world cohort and 8.0% (34/423) in the TCGA cohort. The mutation rates for multiple cadherin sites were 2.5% (6/236) and 2.1% (9/423) in the real-world and TCGA cohorts, respectively. Survival analysis revealed that patients with FAT4 mutations had a significantly better prognosis compared to those with wild-type FAT4 (p=0.0357). Patients with multiple cadherin mutations had a better prognosis compared to those with single cadherin mutations in real-world cohorts (p=0.0651). No significant difference was observed in the TCGA cohort between single and multiple cadherin mutations (p = 0.2003), although FAT4 mutations exhibited a significant improvement in prognosis compared to wild-type patients in the TCGA cohort (p = 0.0226). Conclusion: Our findings indicate that FAT4 mutations confer a favorable prognosis in gastric cancer patients. The presence of FAT4 mutations was associated with improved survival compared to patients with wild-type FAT4. These findings underscore the potential value of FAT4 mutation status as a prognostic factor, guiding personalized treatment approaches for individuals with gastric cancer. Citation Format: Shu Wang, Haoyuan Wang, Yuxuan Ma, Yuhao Wang, Yan Zhao, Chaosheng Peng, Weiming Duan, Feilong Zhao, Jianjun Yang. Gastric cancer carrying FAT4 mutations associated with favorable prognosis in comparison to wild-type: Results from Real-World Cohorts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5133.

Preoperative prediction of lymphovascular and perineural invasion in gastric cancer using spectral computed tomography imaging and machine learning.

Lymphovascular invasion (LVI) and perineural invasion (PNI) are important prognostic factors for gastric cancer (GC) that indicate an increased risk of metastasis and poor outcomes. Accurate preoperative prediction of LVI/PNI status could help clinicians identify high-risk patients and guide treatment decisions. However, prior models using conventional computed tomography (CT) images to predict LVI or PNI separately have had limited accuracy. Spectral CT provides quantitative enhancement parameters that may better capture tumor invasion. We hypothesized that a predictive model combining clinical and spectral CT parameters would accurately preoperatively predict LVI/PNI status in GC patients. To develop and test a machine learning model that fuses spectral CT parameters and clinical indicators to predict LVI/PNI status accurately. This study used a retrospective dataset involving 257 GC patients (training cohort, n = 172; validation cohort, n = 85). First, several clinical indicators, including serum tumor markers, CT-TN stages and CT-detected extramural vein invasion (CT-EMVI), were extracted, as were quantitative spectral CT parameters from the delineated tumor regions. Next, a two-step feature selection approach using correlation-based methods and information gain ranking inside a 10-fold cross-validation loop was utilized to select informative clinical and spectral CT parameters. A logistic regression (LR)-based nomogram model was subsequently constructed to predict LVI/PNI status, and its performance was evaluated using the area under the receiver operating characteristic curve (AUC). In both the training and validation cohorts, CT T3-4 stage, CT-N positive status, and CT-EMVI positive status are more prevalent in the LVI/PNI-positive group and these differences are statistically significant (P < 0.05). LR analysis of the training group showed preoperative CT-T stage, CT-EMVI, single-energy CT values of 70 keV of venous phase (VP-70 keV), and the ratio of standardized iodine concentration of equilibrium phase (EP-NIC) were independent influencing factors. The AUCs of VP-70 keV and EP-NIC were 0.888 and 0.824, respectively, which were slightly greater than those of CT-T and CT-EMVI (AUC = 0.793, 0.762). The nomogram combining CT-T stage, CT-EMVI, VP-70 keV and EP-NIC yielded AUCs of 0.918 (0.866-0.954) and 0.874 (0.784-0.936) in the training and validation cohorts, which are significantly higher than using each of single independent factors (P < 0.05). The study found that using portal venous and EP spectral CT parameters allows effective preoperative detection of LVI/PNI in GC, with accuracy boosted by integrating clinical markers.

The association and clinicopathological significance of Integrin alphavbeta6 and Rac1 expression in gastric carcinoma.

The present study investigate the expression and correlation of ITGB6 and Rac1 proteins in gastric cancer tissues. By exploring the clinical significance and functions of these proteins, we aimed to gain further insights into the mechanisms underlying gastric cancer development. In this study, a total of 198 patients diagnosed with gastric cancer and who underwent gastrectomy between July 2010 to October 2012 were included. The median follow-up time was 52.00 months. To evaluate the factors influencing overall survival, Kaplan-Meier survival curve analysis and Cox regression analysis were conducted. Furthermore, an independent prognostic factor-based nomogram was constructed and validated to predict survival outcomes in gastric cancer patients. In addition, in vitro experiments including CCK8 and Transwell assays were conducted to explore the roles of ITGB6 and Rac1 in gastric cancer. The expression levels of ITGB6 and Rac1 in gastric cancerous and paraneoplastic tissues were detected by immunohistochemistry. The correlation and clinical significance of the two proteins were also investigated. ITGB6 expression showed significant associations with tumor size (P=0.030), pathological grading (P=0.013), location (P=0.031), N stage (P=0.002), and clinical stage (P=0.002). Additionally, we found that tumor size (P=0.013), tumor's anatomical location (P=0.031), N stage (P=0.002), clinical stage (P=0.035), and survival status (P<0.001) were significantly associated with the expression of Rac1. ITGB6 was moderately correlated with Rac1 (r=0.285, P<0.001). Both the Kaplan-Meier survival analysis and Cox regression model analysis demonstrated that the presence of positive expression of ITGB6 and Rac1 proteins served as independent prognostic factors for gastric cancer. These findings highlight the potential of ITGB6 and Rac1 as valuable markers for predicting the prognosis of gastric cancer patients (HR=2.212 P<0.001 and HR=2.073 P=0.001), with a significant poorer trend for 5-year survival (P<0.0001, respectively, the log-rank test). Additionally, subsequent in vitro experiments preliminarily demonstrated that ITGB6 and Rac1 promoted the proliferation, migration and invasion of gastric cancer cells, and ITGB6 may functions via targeting Rac1. ITGB6 and Rac1 are indicators of poor prognosis and tumor progression in gastric cancer patients. The potential signaling pathways associated with both may provide useful targets for the prevention and treatment of gastric cancer.

CA19‑9 is a significant prognostic factor in stage III gastric cancer patients undergoing radical gastrectomy

BackgroundDue to the great heterogeneity of gastric cancer (GC), the prognosis of patients within a stage is very different. Therefore, it is necessary to identify the high risk factors for postoperative recurrence and metastasis and take appropriate therapeutic strategies to improve the prognosis of patients. In this study, we aimed to explore the prognostic significance of preoperative and postoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen 19 − 9 (CA19-9) and carbohydrate antigen 72 − 4 (CA72-4) in patients with stage I, II and III GC who underwent radical gastrectomy.MethodsA total of 580 patients who underwent curative surgical resection and had not received neoadjuvant chemotherapy were included in this study. The relationship between clinicopathological features and recurrence was analysed. Survival analysis was performed by Kaplan–Meier curve. Univariate and multivariate Cox regression analyses were performed to determine prognostic factors in GC patients.ResultsAmong patients with stage III GC, the recurrence free survival (RFS) and overall survival (OS) of patients with CA19-9>35 U/mL were significantly lower than those with CA19-9 ≤ 35 U/mL; CA19-9 was always a significant independent marker. CEA and CA72-4 were sometime useful to predict RFS or OS alternatively in the pre- or postoperative period. The only other independent significant factors for prognosis in our study were lymph node metastases for RFS and postoperative adjuvant chemotherapy for OS.ConclusionPreoperative and postoperative CA19-9 values are independent risk factors for predicting prognosis in stage III GC after curative gastrectomy.

Ensemble Deep Learning Model to Predict Lymphovascular Invasion in Gastric Cancer.

Lymphovascular invasion (LVI) is one of the most important prognostic factors in gastric cancer as it indicates a higher likelihood of lymph node metastasis and poorer overall outcome for the patient. Despite its importance, the detection of LVI(+) in histopathology specimens of gastric cancer can be a challenging task for pathologists as invasion can be subtle and difficult to discern. Herein, we propose a deep learning-based LVI(+) detection method using H&E-stained whole-slide images. The ConViT model showed the best performance in terms of both AUROC and AURPC among the classification models (AUROC: 0.9796; AUPRC: 0.9648). The AUROC and AUPRC of YOLOX computed based on the augmented patch-level confidence score were slightly lower (AUROC: -0.0094; AUPRC: -0.0225) than those of the ConViT classification model. With weighted averaging of the patch-level confidence scores, the ensemble model exhibited the best AUROC, AUPRC, and F1 scores of 0.9880, 0.9769, and 0.9280, respectively. The proposed model is expected to contribute to precision medicine by potentially saving examination-related time and labor and reducing disagreements among pathologists.

Significance of Preoperative Tooth Loss in Patients Who Underwent Gastrectomy for Gastric Cancer.

The relationship between gastric cancer and oral health has been reported in several studies. This study aimed to determine the relationship between the postoperative prognosis of gastric cancer and oral health using preoperative tooth loss as a simple index. We conducted a single-center retrospective cohort study. Patients were divided into two groups according to the number of tooth losses. The survival curve was constructed using the Kaplan-Meier method. We also performed univariate and multivariate analyses of overall survival based on Cox proportional hazard regression to determine prognostic factors. A total of 191 patients were divided into two groups: those with seven or more tooth losses and those with less than seven tooth losses. The three-year overall survival rate was 71.5% in the group with seven or more tooth losses and 87.0% in the group with less than seven tooth losses. The group with seven or more tooth losses had a significantly lower overall survival rate compared to the group with less than seven tooth losses (p=0.0014). However, in multivariate analysis, tooth loss was not identified as an independent prognostic factor whereas age, clinical T stage, CEA level, and serum albumin level were independent poor prognostic factors. Preoperative tooth loss was not a prognostic factor for gastric cancer after gastrectomy, but tooth loss may be a simple and useful method for evaluating frailty in patients.

CSK may be a potential prognostic biomarker reflecting the immune status of gastric cancer.

C-terminal Src kinase (CSK), a sarcoma (Src) homologous family kinase, is one of the most important negative regulators. It acts as a tumor suppressor by inhibiting the activity of Src family tyrosine kinases. Paradoxically, CSK is highly expressed in a variety of common tumors. Therefore, we report the expression profile of CSK in pan-cancer patients, focusing on the prognostic value, immune infiltration pattern, and biological function of CSK in gastric cancer. We used the TCGA database to analyze CSK expression, clinical relevance, prognostic significance, assessment of the tumor immune microenvironment, and GO and Kegg enrichment analysis based on co-expressed genes using a bioinformatics approach. CSK is a protective factor in gastric cancer, and its expression correlates with the level of immune cell infiltration and immune checkpoint molecules. Our findings suggest that CSK is an independent prognostic factor in gastric cancer and may predict molecular targeting and immunotherapy and provide ideas for its therapeutic strategy.

Analysis of Related Risk Factors and Prognostic Factors of Gastric Cancer with Liver Metastasis: A SEER and External Validation Based Study.

Gastric cancer (GC) has a poor prognosis, particularly in patients with liver metastasis (LM). This study aims to identify relevant factors associated with the occurrence of LM in GC patients and factors influencing the prognosis of gastric cancer with liver metastasis (GCLM) patients, in addition to developing diagnostic and prognostic nomograms specifically. Overall, 6184 training data were from the Surveillance, Epidemiology, and End Results (SEER) database from 2011 to 2015. 1527 validation data were from our hospital between January 2018 and December 2022. Logistic regression was used to identify the risk factors associated with the occurrence of LM in GC patients, Cox regression was used to confirm the prognostic factors of GCLM patients. Two nomogram models were established to predict the risk and overall survival (OS) of patients with GCLM. The performance of the two models was evaluated using the area under the curve (AUC), concordance index (C-index), and calibration curves. A nomogram included five independent factors from multivariate logistic regression: sex, lymph node removal, chemotherapy, T stage and N stage were constructed to calculate the possibility of LM. Internal and external verifications of AUC were 0.786 and 0.885, respectively. The other nomogram included four independent factors from multivariate Cox regression: surgery at primary site, surgery at other site, chemotherapy, and N stage were constructed to predict OS. C-index for internal and external validations were 0.714 and 0.702, respectively, and the calibration curves demonstrated the robust discriminative ability of the models. Based on the SEER database and validation data, we defined effective nomogram models to predict risk and OS in patients with GCLM. They have important value in clinical decision-making and personalized treatment.

OGC O07 The prognostic role of positive peritoneal cytology in gastric cancer

Abstract Background Locally advanced non-metastatic gastric cancer is primarily managed with surgical resection and peri-operative oncological therapies. Positive peritoneal cytology is often considered to be indicative of disseminated malignancy. We have previously shown that conversion from positive (Cy+) to negative (Cy0) cytology with systemic therapy, and absence of macroscopic disease, improves survival. With the advent of novel chemo- and radiotherapy regimes as well as immunotherapy, we recognise a lack of current understanding of the role of peritoneal cytology as a prognostic factor. Our study aims to determine the role of positive peritoneal cytology as a prognostic factor in gastric cancer. Methods This is an international multi-centre retrospective cohort study including high-volume, gastric cancer tertiary referral centres. Adult patients without macroscopic metastatic disease who underwent peritoneal cytology, and subsequently multi-modality treatment including surgical resection between 2011 and 2021 were included. The primary outcome measure is overall survival at 1, 3 and 5 years. Secondary outcome measures include recurrence-free survival at 1, 3 and 5 years; 30-day and 90-day major postoperative morbidity; and subset survival analyses were performed in patients who converted to Cy0 in restaging laparoscopy after neoadjuvant therapy. Statistical analysis was performed using R software. Results This is an interim analysis of the data of 280 patients with a mean age of 64.9 (0.72). 231 patients received pre-operative chemotherapy. 51.0% underwent open gastrectomy (41.2% laparoscopic and 4.64% robotic). 55% of patients underwent a total gastrectomy. 25.9% patients had positive cytology on laparoscopy, while 9.71% had indeterminate cytology. There was significant variation in the sites of peritoneal washings (Figure 1). So far, only 1 patient has shown conversion from positive to negative cytology after oncological therapy. At 1 year, the mortality rate was 41.5% (figure 2), while the recurrence rate was 41.4%. Conclusions In this interim report, we demonstrate significant heterogeneity in the way peritoneal cytology is performed, and the peri-operative management of this cohort. The POPEC study closes to patient recruitment at the end of August 2023, and thus at AUGIS we plan to report on the final findings of this study with an anticipated sample size of over 1000 patients.

Risk factors and clinical significances for retropancreatic lymph node metastasis in gastric cancer patients.

The incidence of retropancreatic lymph node metastasis in gastric cancer patients is not negligible. The aim of present study was to determine the risk factors for retropancreatic lymph node (LN) metastasis and to investigate its clinical significance. Clinical pathologic data of 237 patients with gastric cancer between June 2012 and June 2017 were analyzed retrospectively. 14 patients (5.9%) had retropancreatic LN metastases. The median survival of patients with and without retropancreatic LN metastasis was 13.1 and 25.7 months. According to univariate analysis; tumor size ≥ 8 cm, Bormann type III/IV, undifferentiated type, presence of angiolymphatic invasion, depth of invasion (pT4), N3 stage, No. 3, No. 7, No. 8, No. 9, and No. 12p LN metastasis was found to be associated with retropancreatic LN metastasis. According to multivariate analysis; tumor size ≥ 8 cm, Bormann type III/IV, undifferentiated type, pT4, N3 stage, No. 9 LN metastasis, and No. 12p LN metastasis were found to be independent prognostic variables for retropancreatic LN metastasis. Retropancreatic LN metastasis is a poor prognostic factor for gastric cancer. Tumor size (≥ 8 cm), Bormann type III/IV, undifferentiated tumor, pT4, N3 stage, and No. 9 and No. 12p LN metastasis are risk factors for metastasis to retropancreatic lymph node.

GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progresses of gastric cancer

Glutamate-ammonia ligase (GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer.

Nomogram Based on Body Composition and Prognostic Nutritional Index Predicts Survival After Curative Resection of Gastric Cancer

This study aimed to identify independent prognostic factors for gastric cancer (GC) patients after curative resection using quantitative computed tomography (QCT) combined with prognostic nutritional index (PNI), and to develop a nomogram prediction model for individualized prognosis. This study retrospectively analyzed 119 patients with GC who underwent curative resection from January 2016 to March 2018. The patients' preoperative clinical pathological data were recorded, and all patients underwent QCT scans before and after curative resection to obtain QCT parameters: bone mineral density (BMD), skeletal muscle area (SMA), visceral fat area (VFA), subcutaneous fat area (SFA) and CT fat fraction (CTFF), then relative rate of change in each parameter (ΔBMD, ΔSMA, ΔVFA, ΔSFA, ΔCTFF) was calculated after time normalization. Multivariate Cox proportional hazards was used to establish a nomogram model that based on independent prognostic factors. The concordance index (C-index), area under the time-dependent receiver operating characteristic (ROC) curve and clinical decision curve were used to evaluate the predictive performance and clinical benefit of the nomogram model． RESULTS: This study found that ΔCTFF, ΔVFA, ΔBMD and PNI are independent prognostic factors for overall survival (OS)(hazard ratio: 1.034, 0.895, 0.976, 2.951, respectively, all p<0.05). The established nomogram model could predict the area under the ROC curveof OS at 1, 3and 5 years as 0.816, 0.815 and 0.881, respectively. The C-index was 0.743 (95% CI, 0.684-0.801), and the decision curve analysis showed that this model has good clinical net benefit. The nomogram model based on body composition and PNI is reliable in predicting the individualized survival of underwent curative resection for GC patients.

Postoperative ratio of C-reactive protein to albumin is an independent prognostic factor for gastric cancer

ObjectiveThe role of postoperative of the ratio of c-reactive protein to albumin (CRP/Alb ratio) in the prognosis of gastric cancer is rarely evaluated. Our purpose was to investigate the correlation of the postoperative CRP/Alb ratio and long-term prognosis of gastric cancer.MethodsWe enrolled 430 patients who suffered from radical gastrectomy. The commonly used inflammatory indices, clinical-pathological characteristics and oncologic outcomes were recorded. The median was used to the cut-off value for preoperative and postoperative CRP/Alb ratio, respectively. Kaplan–Meier analysis and Cox proportional hazards regression model were performed to determine its prognostic significance.ResultsIn univariate analysis, there were significant differences were observed in overall survival (OS) according to perioperative CRP/Alb ratio, c-reactive protein (CRP), serum albumin (Alb), respectively. According to the multivariate analysis, higher postoperative CRP/Alb ratio (HR 2.03, 95% CI 1.55–2.66, P < 0.001), lower postoperative albumin (Alb), higher preoperative c-reactive protein (CRP) and higher postoperative CRP were indicated a shorter overall survival.ConclusionPostoperative inflammatory factors in patients with gastric cancer should be pay attention, especially postoperative CRP/Alb ratio may be an independent predictor of long-term prognosis of gastric cancer.

Prognostic value of a predictive model comprising preoperative inflammatory response and nutritional indexes in patients with gastric cancer

Objective: To investigate the prognostic value of preoperative inflammatory and nutritional condition detection in the postoperative survival, and establish a prognostic model for predicting the survival of patients with gastric cancer. Methods: The clinicopathological data of 1123 patients with gastric cancer who had undergone radical gastrectomy in Tianjin Medical University Cancer Institute & Hospital from January 2005 to December 2014 were retrospectively analyzed. Patients with history of other malignancy, with history of gastrectomy, who had received preoperative treatment, who died during the initial hospital stay or first postoperative month, and missing clinical and pathological information were excluded. Cox univariate and multivariate analyses were used to identify independent clinicopathological factors associated with the survival of these gastric cancer patients. Cox univariate analysis was used to identify preoperative inflammatory and nutritional indexes related to the survival of patients with gastric cancer after radical gastrectomy. Moreover, the Cox proportional regression model for multivariate survival analysis (forward stepwise regression method based on maximum likelihood estimation) was used. The independent clinicopathological factors that affect survival were incorporated into the following three new prognostic models: (1) an inflammatory model: significant preoperative inflammatory indexes identified through clinical and univariate analysis; (2) a nutritional model: significant preoperative nutritional indexes identified through clinical and univariate analysis; and (3) combined inflammatory/nutritional model: significant preoperative inflammatory and nutritional indexes identified through clinical and univariate analysis. A model that comprised only pT and pN stages in tumor TNM staging was used as a control model. The integrated area under the receiver operating characteristic curve (iAUC) and C-index were used to evaluate the discrimination of the model. Model fitting was evaluated by Akaike information criterion analysis. Calibration curves were used to assess agreement between the predicted probabilities and actual probabilities at 3-year or 5-year overall survival (OS). Results: The study cohort comprised 1 123 patients with gastric cancer. The mean age was 58.9±11.6 years, and 783 were males. According to univariate analysis, age, surgical procedure, extent of lymph node dissection, tumor location, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and nerve invasion were associated with 5-year OS after radical gastrectomy for gastric cancer (all P<0.050). Multivariate analysis further identified age (HR: 1.18, 95%CI: 1.03-1.36, P=0.019), maximum tumor size (HR: 1.19, 95%CI: 1.03-1.38, P=0.022), number of examined lymph nodes (HR: 0.79, 95%CI: 0.68-0.92, P=0.003), pT stage (HR: 1.40, 95%CI: 1.26-1.55, P<0.001) and pN stage (HR: 1.28, 95%CI: 1.21-1.35, P<0.001) as independent prognostic factors for OS of gastric cancer patients. Additionally, according to univariate survival analysis, the preoperative inflammatory markers of neutrophil count, percentage of neutrophils, neutrophil/lymphocyte ratio, platelet/neutrophil ratio and preoperative nutritional indicators of serum albumin and body mass index were potential prognostic factors for gastric cancer (all P<0.05). On the basis of the above results, three models for prediction of prognosis were constructed. Variables included in the three models are as follows. (1) Inflammatory model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, and neutrophil-lymphocyte ratio; (2) nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and serum albumin; and (3) combined inflammatory/nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, neutrophil-lymphocyte ratio, and serum albumin. We found that the predictive accuracy of the combined inflammatory/nutritional model, which incorporates both inflammatory indicators and nutrition indicators (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.698),was superior to that of the inflammation model (iAUC: 0.662, 95% CI: 0.673-0.706;C-index: 0.675), nutritional model (iAUC: 0.666, 95% CI: 0.642-0.698, C-index: 0.672), and TNM staging control model (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.658). Furthermore, the combined inflammatory/nutritional model had better fitting performance (AIC: 10 762) than the inflammatory model (AIC: 10 834), nutritional model (AIC: 10 810), and TNM staging control model (AIC: 10 974). Conclusions: Preoperative percentage of neutrophils, NLR, and BMI have predictive value for the prognosis of gastric cancer patients. The inflammatory / nutritional model can be used to predict the survival and prognosis of gastric cancer patients on an individualized basis.

Application and significance of circRNA and high throughput sequencing in different metastatic pathways of gastric cancer

In this study, we will explore the expression profile of circular RNA (cRNA) in gastric cancer tissues and plasma in order to evaluate its potential as a molecular marker for the detection of gastric cancer. Additionally, we will research the expression profile of cRNA in normal gastric tissue. Reverse transcription drop digital polymerase chain reaction (RT ddPCR), circRNA expression profiling, the prediction of circRNA-microRNA interactions, the design of a method for RT ddPCR, as well as the analysis of clinicopathological factors and survival outcomes are all included in the recommended approach. The results of the research indicate that some circRNAs have a distinct expression pattern in the plasma and tissues of patients with gastric cancer. In addition, a quantitative RT ddPCR approach was created, and the identification of certain circRNAs that are connected with clinicopathological factors and prognosis was accomplished. The results of this study provide significant new insights into the ability of circRNAs to function not only as diagnostic markers but also as independent prognostic factors for gastric cancer. In addition, a dye-based RT ddPCR method is shown to be an effective and economical technique for the detection of plasma circRNA.

The high expression of glial cell line-derived neurotrophic factor receptor alpha Ⅱ (GFRA2) as a predictor of poor prognosis in gastric cancer patients: A survival and regression analysis approach

Gastric cancer has high mortality rates worldwide. Therefore, there is a need to identify prognostic biomarkers. This study evaluated the association between GFRA2 expression levels with clinicopathological features and prognosis in gastric cancer using data extracted from The Cancer Genome Atlas (TCGA) database and a series of algorithms. Survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were used to analyze the association between different clinical features and survival. Single-sample gene set enrichment analysis (GSEA) was used to examine the correlation between GFRA2 expression and immune infiltration. The results showed that the expression of GFRA2 in tumor samples was significantly lower than that in normal samples. High expression of GFRA2 was significantly associated with histological type, histologic grade, and worse overall survival, disease-specific survival, and progression-free survival. The univariate Cox analysis showed that the expression of GFRA2 was significantly correlated with T stage, N stage, M stage, and age. The multivariate analysis identified GFRA2 expression as an independent prognostic factor for gastric cancer. GSEA showed that GFRA2 might regulate the calcium signaling pathway, focus adhesion, olfactory conduction, the extracellular matrix glycoproteins, and response to the Leishmania parasitic infection. GFRA2 showed a significant moderate positive correlation with the infiltration of mast cells. In summary, a high expression of GFRA2 may contribute to poor survival in gastric cancer patients and could be used as a potential prognostic biomarker.