Survival In Gastric Cancer Research Articles

HLA-G high-expressor 3'UTR markers are linked to gastric cancer development and survival.

Gastric cancer ranks fifth in both world prevalence and lethality, with a 5-year survival of less than 30%. HLA-G, a non-classical class I HLA gene, has emerged as a potential marker for cancer susceptibility and prognosis due to its immunomodulatory properties. Its level of expression is regulated by polymorphisms in the 3' untranslated region (3'UTR) polymorphisms, which form various combined haplotypes (UTR-1 to -9). In this study, we examined HLA-G 3'UTR polymorphisms in paired tissue samples from 111 patients with gastric adenocarcinoma and 119 healthy controls. Polymorphism analysis was performed using PCR and Sanger sequencing, followed by statistical analysis using SNPStats software. Survival analysis was conducted using Kaplan-Meier curves and multivariate Cox regression models. High-expressor HLA-G 3'UTR haplotypes (UTR-1 and UTR-6) were significantly associated with gastric cancer susceptibility, indicating a potential role in tumor immune evasion. Additionally, the 14 base pair insertion/deletion polymorphism (14bp I/D) emerged as a prognostic marker, with D/D genotype carriers showing lower survival rates compared to I/D and I/I genotype carriers. Our study highlights the clinical relevance of HLA-G polymorphisms in gastric cancer, suggesting their potential as prognostic markers and therapeutic targets. Further elucidation of HLA-G-related pathways could lead to personalized treatment strategies and improved patient outcomes in gastric cancer.

Development and validation of a nomogram to predict the survival and estimate surgical benefits for gastric cancer with liver metastasis receiving primary tumor resection

BackgroundSurgical treatment has been widely controversial for gastric cancer accompanied by liver metastasis (GCLM). This paper aims to develop and validate a nomogram to predict the survival and estimate surgical benefits for GCLM patients.MethodsA total of 616 GCLM patients from the Surveillance, Epidemiology, and End Results Program (SEER) database and 74 GCLM patients receiving primary tumor resection (PTR) from the Chinese center were included in this study. Patients from the SEER database were divided into training set (with PTR) (n=493) and non-operative set (without PTR) (n=123). Patients undergoing PTR from China were included as external validation set. Independent risk factors associated with the overall survival of GCLM patients undergoing PTR were identified in the training set via log-rank test and Cox regression analysis. Afterwards, a comprehensive model and corresponding nomogram were constructed and validated by validation set.ResultsThe survival of patients undergoing PTR (n=493) was longer than that without PTR (n=123) (log-rank test, p<0.0001) in SEER cohort. T stage (HR=1.40, 95% CI=1.14, 1.73), differentiation grade (HR=1.47, 95% CI=1.17, 1.85), non-hepatic metastases (HR=1.69, 95% CI=1.29, 2.21), and adjuvant therapy (HR=0.34, 95% CI= 0.28, 0.42) were closely related with the survival of GCLM with PTR, and thus, a four-factor nomogram was established. However, GCLM patients receiving PTR in the high-risk subgroup (n=255) screened out by the nomogram did not have better survival outcomes compared with patients without PTR (n=123) (log-rank test, p=0.25).ConclusionsThe nomogram could predict survival of GCLM patients receiving PTR with acceptable accuracy. In addition, although PTR did improve the survival of whole GCLM patients, patients in the high-risk subgroup were unable to benefit from PTR, which could assist clinicians to make decisions for the treatment of GCLM.

Impact of gastrectomy on efficacy and safety of second‐line chemotherapy patients with advanced gastric cancer: Exploratory analysis of two randomized phase III trials

AbstractAimsSecond‐line chemotherapy (SLC) improves survival in advanced gastric cancer (AGC). Although many patients receiving SLC have undergone gastrectomy, the impact of gastrectomy on SLC remains unclear.Patients and MethodsThe objective was to evaluate the impact of gastrectomy on SLC for AGC. A total of 290 eligible patients registered in two randomized phase III trials evaluating SLC for patients with AGC was classified into the prior gastrectomy group (PGG; n = 187) or the no gastrectomy group (NGG; n = 103). We compared overall survival (OS), progression‐free survival (PFS), overall response rate (ORR), disease control rate (DCR), and safety between these two groups. Adjusted OS and adjusted PFS were estimated using inverse probability of treatment weighting (IPTW).ResultsThe PGG had better performance status (p = 0.001), more prior platinum agent (p < 0.001), and more frequent peritoneal metastasis (p = 0.006) than the NGG. The PGG had significantly better OS (13.8 vs. 9.3 mo; hazard ratio [HR]: 0.59; p < 0.001) and PFS (4.7 vs. 2.8 mo; HR: 0.58; p < 0.001) than the NGG. The PGG had significantly better adjusted OS (13.8 vs. 10.0 mo; IPTW HR: 0.66; p = 0.01) and adjusted PFS (4.3 vs. 3.2 mo; IPTW HR: 0.71; p = 0.027) than the NGG. No significant differences were observed in ORR and DCR. The incidence of Grade 3 or worse adverse events did not differ between the two groups except for a high incidence of anemia and diarrhea in the NGG.ConclusionPatients with previous gastrectomy are expected to have better survival outcomes when receiving second‐line irinotecan (IRI)‐based chemotherapy for AGC.

A CXCR4 partial agonist improves immunotherapy by targeting polymorphonuclear myeloid-derived suppressor cells and cancer-driven granulopoiesis.

Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are pathologically activated neutrophils that potently impair immunotherapy responses. The chemokine receptor CXCR4, a central regulator of hematopoiesis, represents an attractive PMN-MDSC target1. Here, we fused a secreted CXCR4 partial agonist TFF2 to mouse serum albumin (MSA) and demonstrated that TFF2-MSA peptide synergized with anti-PD-1 to induce tumor regression or eradication, inhibited distant metastases, and prolonged survival in multiple gastric cancer (GC) models. Using histidine decarboxylase (Hdc)-GFP transgenic mice to track PMN-MDSC in vivo , we found TFF2-MSA selectively reduced the immunosuppressive Hdc-GFP + CXCR4 hi tumor PMN-MDSCs while preserving proinflammatory neutrophils, thereby boosting CD8 + T cell-mediated anti-tumor response together with anti-PD-1. Furthermore, TFF2-MSA systemically reduced PMN-MDSCs and bone marrow granulopoiesis. In contrast, CXCR4 antagonism plus anti-PD-1 failed to provide a similar therapeutic benefit. In GC patients, expanded PMN-MDSCs containing a prominent CXCR4 + LOX-1 + subset are inversely correlated with the TFF2 level and CD8 + T cells in circulation. Collectively, our studies introduce a strategy of using CXCR4 partial agonism to restore anti-PD-1 sensitivity in GC by targeting PMN-MDSCs and granulopoiesis.

IGFL2 expression and surgical volume: Independent predictors of survival in gastric cancer.

This study aimed to assess the impact of surgeons' annual volume and insulin-like growth factor-like family member 2 (IGFL2) expression on gastric cancer prognosis. Clinicopathological data from 475 patients who underwent D2 lymph node dissection were analyzed. IGFL2 expression was evaluated using immunohistochemistry. Patients were divided into training (70%) and validation (30%) groups. Univariate and multivariate Cox regression identified risk factors for overall survival (OS) and disease-free survival (DFS), leading to a clinical prediction model. Model performance was evaluated using C-index. High IGFL2 expression and low surgical volume independently predicted poorer OS and DFS (hazard ratio = 2.13, 2.17, all P < .01). Surgeons performing >26 cases annually had higher OS and DFS (hazard ratio = 1.65, 1.58, all P < .01). Nomograms integrating surgical volume, IGFL2 expression, grade, TNM staging, and carcinoembryonic antigen showed superior predictive accuracy for OS and DFS compared to TNM alone, with robust C-indices and area under the curve values. Surgeons' annual volume and IGFL2 expression independently predict gastric cancer prognosis, emphasizing the need for specialized training and further research on IGFL2's molecular mechanisms to enhance patient outcomes.

Capecitabine enhances sensitivity to oxaliplatin in advanced gastric cancer and the effects on patients' FOXP1 and GGT levels

ObjectiveTo investigate the effect of capecitabine on the sensitivity of oxaliplatin and on the level of transcription factor forkhead box P1 (FOXP1) and gamma-glutamyl transpeptidase (GGT) in patients with intermediate and advanced gastric cancer. MethodsA total of 152 patients with intermediate and advanced gastric cancer diagnosed and treated in our hospital from April 2018 to May 2019 was selected as the research objects, and their clinical data were retrospectively analyzed. According to the different treatment methods, they were divided into the study group and the control group, with 76 cases in each group. The patients in the control group received with oxaliplatin, while the patients in the study group received with capecitabine on the basis of the control group. The therapeutic effect was evaluated according to the therapeutic effect evaluation criteria of solid tumors. The FOXP1 expression level in gastric cancer tissues was detected using immunohistochemistry. Serum levels of GGT were measured by chemiluminescence. The prognostic factors were analyzed by COX regression model, and the Kaplan-Meier survival curve was used to analyze the relationship between the influencing factors and the survival of gastric cancer. ResultsThe effective rate of capecitabine combined with oxaliplatin and oxaliplatin alone in the treatment of patients with intermediate and advanced gastric cancer were 94.74% and 76.32% respectively. Capecitabine enhanced the sensitivity of intermediate and advanced gastric cancer to oxaliplatin (P<0.05). Compared with adjacent normal tissues, the expression level of FOXP1 in gastric cancer tissues was lower (P<0.05). Before treatment, the expression of FOXP1 was low, and no significant difference was observed in the GGT level between the two groups (P>0.05). After treatment, the low expression rate of FOXP1 and serum GGT level were both significantly decreased, and those in the study group were lower than those in the control group (P<0.05). There was no difference in the incidence of adverse reactions between the two groups (P>0.05). The 1-year survival rates of the study group and the control group were 90.79% and 78.95%, while the 3-year survival rates of the study group and the control group were 75.00% and 51.32%, respectively. Both the 1-year and 3-year survival rate of the study group was higher than that in the control group (P<0.05). The 1-year survival rate of 152 patients with gastric cancer was 84.87% (129/152) and the 3-year survival rate was 63.17% (96/152). Age, tumor diameter, tumor-node-metastasis (TNM) stage, lymph node metastasis, chemotherapy regimen and the expression of FOXP1 and GGT had significant effects on the survival rate (P<0.05). Gastric cancer patients with age < 60 years, TNM stage of Ⅰ ∼ Ⅱ, lymph node metastasis N0 ∼ N1, high expression of FOXP1, GGT < 387.2, and combined with drug chemotherapy had higher survival rate. ConclusionCapecitabine effectively enhanced the sensitivity of intermediate and advanced gastric cancer to oxaliplatin, improved the therapeutic effect, reduced the proportion of patients with low FOXP1 expression rate and serum GGT level, decreased the recurrence rate and ameliorated the prognosis of patients.This is a retrospective study, all data were analyzed retrospectively. This research was approved by the Ethics Review Committees of Fuwai Central China Cardiovascular Hospital (approval number: 2023-EC-015).

Targeted dynamic phospho-proteogenomic analysis of gastric cancer cells suggests host immunity provides survival benefit

Despite of massive emergence of molecular targeting drugs, the mainstay of advanced gastric cancer (GC) therapy is DNA-damaging drugs. Using a reverse-phase protein array-based proteogenomic analysis of a panel of eight GC cell lines, we identified genetic alterations and signaling pathways, potentially associated with resistance to DNA-damaging drugs, including 5-fluorouracil (5FU), cisplatin, and etoposide. Resistance to cisplatin and etoposide, but not 5FU, was negatively associated with global copy number loss, vimentin expression, and caspase activity, which are considered hallmarks of previously established EMT subtype. The segregation of 19,392 protein expression time courses by sensitive and resistant cell lines for the drugs tested revealed that 5FU-resistant cell lines had lower changes in global protein dynamics, suggesting their robust protein level regulation, compared to their sensitive counterparts, whereas the cell lines that are resistant to other drugs showed increased protein dynamics in response to each drug. Despite faint global protein dynamics, 5FU-resistant cell lines showed increased STAT1 phosphorylation and PD-L1 expression in response to 5FU. In publicly available cohort data, expression of STAT1 and NFκB target genes induced by proinflammatory cytokines was associated with prolonged survival in GC. In our validation cohort, total lymphocyte count (TLC), rather than PD-L1 positivity, predicted a better relapse-free survival rate in GC patients with 5FU-based adjuvant chemotherapy than those with surgery alone. Moreover, TLC+ patients who had no survival benefit from adjuvant chemotherapy were discriminated by expression of IκBα, a potent negative regulator of NFκB. Collectively, our results suggest that 5FU resistance observed in cell lines may be overcome by host immunity or by combination therapy with immune checkpoint blockade.

Gastric Cancer Survival and Its Predictors in Nepal.

In Nepal, gastric cancer was the second most common cause of cancer deaths in males and the fifth most common cause of cancer deaths in females in 2020. Although gastric cancer is a significant public health problem, there have been no studies undertaken in Nepal to determine the survival and predictors of gastric cancer survival. A retrospective cohort study of gastric cancer patients at Bhaktapur Cancer Hospital in Kathmandu Valley, Nepal. Data were analysed from 817 new gastric cancer cases, diagnosed between January 2010 and December 2021. Survival rate was analyzed using Kaplan-Meyer methods, and predictors of gastric cancer survival were analyzed using Cox Regression methods. The median overall survival for gastric cancer patients was 19 months since diagnosis. The five-year survival rate was 12%. The predictors for survival were younger age, tumors located in the non-cardia, early stage, treatment by surgery, and treatment by chemotherapy. However, sex, histologic type, tumor grade, tumor subtype, and extent of cancer were not associated with survival. In Nepal, the overall survival of patients with gastric cancer was 12%, which is much lower than in high-income countries. Predictors of survival were patient age at diagnosis, the stage at diagnosis, the location of the tumor, and the treatment undertaken, both in Nepal and in high-income countries.

P11-6 Effects of trastuzumab therapy on overall survival in HER2-positive gastric cancer: a systematic review

P11-6 Effects of trastuzumab therapy on overall survival in HER2-positive gastric cancer: a systematic review

The impact of neighborhood socioeconomic deprivation on treatment and survival for patients with metastatic gastric cancer: An incidence-based retrospective cohort study.

110 Background: Studies have shown that socioeconomic deprivation (SED) is associated with reduced treatment and overall survival (OS) for gastric cancer. However, these studies have typically used large geographic areas for assessment of SED and aggregated all stages. Using a statewide cancer registry, the Area Deprivation Index, a granular measure of SED, was used to assess receipt of treatment and OS for metastatic gastric cancer patients. Methods: Using the incidence-based Florida Cancer Data System, gastric adenocarcinoma patients diagnosed from 2007-2015were identified (n=8,304). The Area Deprivation Index (ADI) is a composite measure of SED and validated dataset that ranks neighborhoods (census block groups) from 1-100 (higher scores=higher deprivation). Demographic, tumor, and treatment variables were assessed using descriptive statistics, regression, and survival analysis. Results: Overall, 3,050 stage IV patients met inclusion criteria; 53.9% were male and the median age was 67. When assessed by SED quartile, there were significant differences by race, ethnicity, insurance, and receipt of chemotherapy (p&lt;0.05). For the cohort, 55.3% of patients received chemotherapy. However, 61.3% of the lowest deprivation cohort received chemotherapy compared to 50.4% in the highest deprivation cohort (p&lt;0.001). After adjustment for potential confounders, the lowest deprivation quartile had increased odds of chemotherapy compared to the highest deprivation quintile (OR 1.52; 95% CI,1.20-1.92). Of patients who received chemotherapy, the median time in months to initiation was 1.1 (interquartile range 0.6-1.7). Median OS was 5.8 months. The median OS for the lowest and highest SED quartiles was 7.5 and 5.1 months, respectively (p&lt;0.001). For patients who received and did not receive chemotherapy, median OS was 10.0 and 1.9 months, respectively. The median OS of the lowest and highest SED quartiles for those who received chemotherapy was 11.3 and 8.8 months, respectively (p&lt;0.001). Conclusions: In an incidence-based, statewide cancer registry examining metastatic gastric cancer, just over half of patients received chemotherapy and median OS was poor. Additionally, higher SED was associated with lower odds of chemotherapy and worse OS. These data suggest that SED impacts metastatic gastric cancer outcomes and future studies are needed to understand the multilevel factors driving disparities. Lowest Deprivation Low Deprivation High Deprivation Highest Deprivation p-value N=752 N=780 N=747 N=718 Chemotherapy 0.003 No 262 (34.8%) 315 (40.4%) 306 (41.0%) 314 (43.7%) Yes 461 (61.3%) 424 (54.4%) 410 (54.9%) 362 (50.4%) Unknown 29 (3.9%) 41 (5.3%) 31 (4.1%) 42 (5.8%)

Network Pharmacology Study of Compound Ligustrazine in Gastric Cancer Therapy

To explore the potential role and mechanism of compound tetramethylpyrazine in gastric cancer therapy by using network pharmacology analysis combined with gene function annotation and clinical data analysis. SwissTargetPrediction database was used to screen the potential drug action sites of compound tetramethylpyrazine, and the OMIM and Genecard databases were used in combination to obtain gastric cancer-related targets. Intersection analysis was performed to identify potential therapeutic targets. Subsequently, the method of ClusterProfiler was used to perform functional annotation of the downstream targets of intersection. In addition, The Cancer Genome Atlas (TCGA) database was used to obtain the original data of gastric cancer patients, and the immune infiltration analysis, miRNA analysis, transcriptional regulation analysis of key genes, gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), nomogram model construction, and genome-wide association studies (GWAS) were performed. Through network pharmacological screening, we found 14 potential therapeutic targets through which tetramethylpyrazine acted on gastric cancer. Functional annotation showed that these targets were mainly involved in the pathways for hormone metabolism, drug metabolism, and signal transduction. Based on log rank test, the expression of the key genes, ELANE and MPO, showed significant difference in the comparison of gastric cancer survival curves (P<0.05), and were closely associated with immune cell infiltration. In addition, GSEA and GSVA results suggested that ELANE and MPO might influence the development of gastric cancer through multiple signaling pathways. In this study, by using multiple analysis methods in an integrated way, we found that ligustrazine may have therapeutic effects on gastric cancer by regulating the potential targets of ELANE and MPO, as well as the relevant signaling pathways.

Hispanic/Latino Ethnicity is an Independent Predictor of Worse Survival for Gastric Cancer in a Multicenter Safety-Net Patient Population.

Various population-based studies have shown Hispanic/Latino ethnicity is a risk factor for worse survival in patients with gastric cancer linked to disparate access to care. We aimed to address whether Hispanic patients treated within safety-net hospital systems continue to experience this survival deficit compared to non-Hispanic patients. We performed a retrospective cohort study comparing survival between Hispanic and non-Hispanic patients diagnosed with gastric adenocarcinoma between January 1, 2016 to December 31, 2020 within Los Angeles County's safety-net hospital system. Gastric cancer-specific survival was compared between the two cohorts using the Kaplan-Meier estimate and Cox proportional-hazards regression model. 448 patients who received care from five medical centers were included. 348 (77.7%) patients self-identified as Hispanic and 100 (22.3%) as non-Hispanic. Mean follow-up time was 2.0 years (median 0.91 years, IQR, 0.34-2.5 years). Hispanic patients were found to be diagnosed at a younger age (55.6 vs 60.7 years, p <0.01), demonstrate higher state area deprivation index (6.4 vs 5.0, p <0.01), and present with metastatic disease (59.8% vs 45%, p =0.04). After adjusting social and oncologic variables, Hispanic ethnicity remained an independent risk factor for worse survival (HR 1.56, [95% CI 1.06-2.28], p = 0.02). Hispanic patients treated within a large, multi-center safety-net hospital system experience worse survival compared to non-Hispanic patients. This suggests ethnic disparities exist within safety-net hospital systems, independent of known clinicopathologic factors. Improving outcomes for Hispanic patients with gastric cancer requires future efforts aimed at defining and addressing these unidentified barriers to care.

Sex disparity, prediagnosis lifestyle factors, and long-term survival of gastric cancer: a multi-center cohort study from China

BackgroundThis multi-center cohort study aimed to investigate whether sex and prediagnosis lifestyle affect the prognosis of gastric cancer.MethodsPatients with gastric cancer were from four gastric cancer cohorts of the National Cancer Center of China, The First Hospital of Lanzhou University, Lanzhou University Second Hospital, and Gansu Provincial Cancer Hospital. Prediagnosis lifestyle factors in our study included body mass index (BMI) at diagnosis, usual BMI, weight loss, the history of Helicobacter pylori (Hp) infection, and the status of smoking and drinking.ResultsFour gastric cancer cohorts with 29,779 gastric cancer patients were included. In total patients, female patients had a better prognosis than male patients (HR = 0.938, 95%CI: 0.881–0.999, P = 0.046). For prediagnosis lifestyle factors, BMI at diagnosis, usual BMI and the amount of smoking were statistically associated with the prognosis of gastric cancer patients. Female patients with smoking history had a poorer survival than non-smoking females (HR = 0.782, 95%CI: 0.616–0.993, P = 0.044). Tobacco consumption > 40 cigarettes per day (HR = 1.182, 95%CI: 1.035–1.350, P = 0.013) was independent adverse prognostic factors in male patients. Obesity paradox was observed only in male patients (BMI < 18.5, HR = 1.145, 95%CI: 1.019–1.286, P = 0.023; BMI: 23–27.4, HR = 0.875, 95%CI: 0.824–0.930, P < 0.001; BMI ≥ 27.5, HR = 0.807, 95%CI: 0.735–0.886, P < 0.001).ConclusionsSex and some prediagnosis lifestyle factors, including BMI at diagnosis, usual BMI and the amount of smoking, were associated with the prognosis of gastric cancer.

Multitask machine learning-based tumor-associated collagen signatures predict peritoneal recurrence and disease-free survival in gastric cancer.

Accurate prediction of peritoneal recurrence for gastric cancer (GC) is crucial in clinic. The collagen alterations in tumor microenvironment affect the migration and treatment response of cancer cells. Herein, we proposed multitask machine learning-based tumor-associated collagen signatures (TACS), which are composed of quantitative collagen features derived from multiphoton imaging, to simultaneously predict peritoneal recurrence (TACSPR) and disease-free survival (TACSDFS). Among 713 consecutive patients, with 275 in training cohort, 222 patients in internal validation cohort, and 216 patients in external validation cohort, we developed and validated a multitask machine learning model for simultaneously predicting peritoneal recurrence (TACSPR) and disease-free survival (TACSDFS). The accuracy of the model for prediction of peritoneal recurrence and prognosis as well as its association with adjuvant chemotherapy were evaluated. The TACSPR and TACSDFS were independently associated with peritoneal recurrence and disease-free survival in three cohorts, respectively (all P < 0.001). The TACSPR demonstrated a favorable performance for peritoneal recurrence in all three cohorts. In addition, the TACSDFS also showed a satisfactory accuracy for disease-free survival among included patients. For stage II and III diseases, adjuvant chemotherapy improved the survival of patients with low TACSPR and low TACSDFS, or high TACSPR and low TACSDFS, or low TACSPR and high TACSDFS, but had no impact on patients with high TACSPR and high TACSDFS. The multitask machine learning model allows accurate prediction of peritoneal recurrence and survival for GC and could distinguish patients who might benefit from adjuvant chemotherapy.

Histopathological response to chemotherapy and survival of mucinous type gastric cancer.

Data on the clinicopathological characteristics of mucinous gastric cancer (muc-GC) are limited. This study compares the clinical outcome and response to chemotherapy between patients with resectable muc-GC, intestinal (int-GC) and diffuse (dif-GC) gastric cancer. Patients from the D1/D2 study or the CRITICS trial were included in exploratory surgery-alone (SAtest) or chemotherapy test (CTtest) cohorts. Real-world data from the Netherlands Cancer Registry on patients treated between with surgery-alone (SAvalidation), and receiving preoperative chemotherapy with or without postoperative treatment (CTvalidation) were used for validation. Histopathological subtypes were extracted from pathology reports filed in the Dutch Pathology Registry and correlated with tumor regression grade (TRG) and relative survival (RS). In SAtest (n = 549) and SAvalidation (n = 8062) cohorts, muc-GC patients had a five-year RS of 39% and 31%, similar to or slightly better than dif-GC (43% and 29%, p = .52 and p = .011), but worse than int-GC (55% and 42%, p = .11 and p < .001). In CTtest (n = 651) and CTvalidation (n = 2889) cohorts, muc-GC showed favorable TRG (38% and 44% (near-)complete response) compared to int-GC (26% and 35%) and dif-GC (10% and 28%, p < .001 and p = .005). The 5-year RS in CTtest and CTvalidation cohorts for muc-GC (53% and 48%) and int-GC (58% and 59%) was significantly better compared to dif-GC (35% and 38%, p = .004 and p < .001). Recognizing and incorporating muc-GC into treatment decision-making of resectable GC can lead to more personalized and effective approaches, given its favorable response to preoperative chemotherapy in relation to int-GC and dif-GC and its favorable prognostic outcomes in relation to dif-GC.

Trends of older gastric cancer incidence, mortality, and survival in the highest gastric cancer risk area in China: 2010–2019 and prediction to 2024

BackgroundGastric cancer is a major health problem worldwide, with a high incidence among older adults. Given the aging overall population, it was crucial to understand the current burden and prospective trend of older gastric cancer. This study aimed to analyze the temporal trends of the incidence, mortality, and survival of older gastric cancer in the highest gastric cancer risk area in China from 2010 to 2019, and to predict the future burden of older gastric cancer up to 2024.MethodsThe study was conducted in Gansu province, an area characterized by the highest gastric cancer incidence and mortality in China. The registration data of gastric cancer incidence and mortality from 2010 to 2019 were pooled from registries in the Gansu Cancer Registration System, while survival data were collected from the First Hospital of Lanzhou University, Lanzhou University Second Hospital, and Gansu Cancer Hospital. Chinese standard population in 2000 and the Segi’s world standard population were applied to calculate the age-standardized rate. Joinpoint regression was used to analyze the average annual percentage change (AAPC) in cancer incidence and mortality. Autoregressive Integrated Moving Average (ARIMA) models were employed to generate forecasts for incidence and mortality from 2020 to 2024.ResultsBased on registry data from 2010 to 2019, the incidence and mortality rates of gastric cancer among older adults remained stable. The incidence rates declined from 439.65 per 100,000 in 2010 to 330.40 per 100,000 in 2019, with an AAPC of -2.59% (95% confidence interval[CI], -5.14 to 0.04, P = 0.06). Similarly, the mortality rate changed from 366.98 per 100,000 in 2010 to 262.03 per 100,000 in 2019, with an AAPC of -2.55% (95% CI, -8.77–4.08%, P = 0.44). In the hospital-based cohort, the decline in survival rates was reported among older patients with gastric cancer in the highest gastric cancer risk area in China, with the 3-year overall survival (OS) decreasing from 58.5% (95% CI, 53.5–63.2%) in 2010 to 34.4% (95%CI, 32.1–36.7%) in 2019, and the 3-year progression-free survival (PFS) decreasing from 51.3% (95%CI, 47.5–55.1%) in 2010 to 34.2% (95%CI, 32.0–36.3%) in 2019, respectively. Moreover, forecasts generated by ARIMA models revealed a significant decline in the incidence and mortality of older gastric cancer in China from 2020 to 2024. Specifically, the incidence rate of older gastric cancer was expected to decrease from 317.94 per 100,000 population in 2020 to 205.59 per 100,000 population in 2024, while the anticipated mortality rate was estimated to decrease from 222.52 per 100,000 population in 2020 to 186.22 per 100,000 population in 2024.ConclusionFrom 2010 to 2019, the incidence and mortality of older gastric cancer remained stable in the highest gastric cancer risk area in China, while the survival rates showed a decline. Based on the ARIMA models, it was anticipated that there might be a continued decline in older gastric cancer incidence and mortality in the highest-risk area in China over the next five years.

1418P Tumor microenvironment B-cell abundance and survival in resectable gastric cancer: A translational analysis from the CLASSIC trial

1418P Tumor microenvironment B-cell abundance and survival in resectable gastric cancer: A translational analysis from the CLASSIC trial

Prognostic signature and immune landscape of 5-methylcytosine-related long non-coding RNAs in gastric cancer

BackgroundLong non-coding RNAs (lncRNAs) have been demonstrated to be useful in assessing the prognosis of cancer patients. However, few studies have focused on 5-methylcytosine-related lncRNAs (m5C-lncRNAs) in gastric cancer (GC). In this study, we aimed to establish a m5C-lncRNAs prognostic signature (m5C-LPS) and explore its potential impact on guiding clinical practice for GC. MethodsRNA-sequence and clinicopathological data were retrieved from The Cancer Genome Atlas (TCGA) database, while the coexpression of long non-coding RNAs (lncRNAs) was determined using Pearson's correlation analysis. A m5C-LPS model was constructed using univariate and Lasso Cox regression, and its prognostic value and accuracy were subsequently validated. Subsequently, the expression of 11 m5C-lncRNAs was verified via quantitative real-time PCR (qRT-PCR) in gastric cancer (GC) cell lines. The potential biological mechanism of this signature was elucidated using Gene Set Enrichment Analysis (GSEA). Based on the GSEA findings, CIBERSORT and ESTIMATE algorithms were utilized to conduct a comprehensive investigation of the tumor immune microenvironment (TIME) in GC. Additionally, pRRophetic and TIDE algorithms were employed to predict drug sensitivity and the efficacy of immunotherapy for GC patients. Results280 lncRNAs were identified as m5C-lncRNAs, including RHPN1-AS1, AC093752.3, TSC22D1-AS1, AL391152.1, MAGI2-AS3, AC048382.2, AL033527.3, AC007405.2, AC036103.1, CCDC183-AS1, and ADORA2A-AS1. Their prognostic value was validated, and the expression of these 11 lncRNAs was confirmed in four gastric cancer cell lines using quantitative reverse transcription PCR (qRT-PCR). A nomogram incorporating a risk score was developed to provide more precise clinical decision-making. Gene Set Enrichment Analysis (GSEA) showed that many classical signaling pathways related to tumor progression were enriched in this signature. Analyses related to immunity and drug sensitivity demonstrated distinct differences in features between high-risk and low-risk subgroups. ConclusionThe m5C-LPS can predict the survival of gastric cancer (GC) patients, provide novel therapeutic targets, and thus offer more thoughtful perspectives for future clinical decisions regarding GC.

Impact of body composition parameters, age, and tumor staging on gastric cancer prognosis.

Research studies on gastric cancer have not investigated the combined impact of body composition, age, and tumor staging on gastric cancer prognosis. To address this gap, we used machine learning methods to develop reliable prediction models for gastric cancer. This study included 1,132 gastric cancer patients, with preoperative body composition and clinical parameters recorded, analyzed using Cox regression and machine learning models. The multivariate analysis revealed that several factors were associated with recurrence-free survival (RFS) and overall survival (OS) in gastric cancer. These factors included age (≥65 years), tumor-node-metastasis (TNM) staging, low muscle attenuation (MA), low skeletal muscle index (SMI), and low visceral to subcutaneous adipose tissue area ratios (VSR). The decision tree analysis for RFS identified six subgroups, with the TNM staging I, II combined with high MA subgroup showing the most favorable prognosis and the TNM staging III combined with low MA subgroup exhibiting the poorest prognosis. For OS, the decision tree analysis identified seven subgroups, with the subgroup featuring high MA combined with TNM staging I, II showing the best prognosis and the subgroup with low MA, TNM staging II, III, low SMI, and age ≥65 years associated with the worst prognosis. Cox regression identified key factors associated with gastric cancer prognosis, and decision tree analysis determined prognoses across different risk factor subgroups. Our study highlights that the combined use of these methods can enhance intervention planning and clinical decision-making in gastric cancer.

Development and External Validation of a CT-Based Radiomics Nomogram to Predict Perineural Invasion and Survival in Gastric Cancer: A Multi-institutional Study

Rationale and ObjectivesTo develop and validate a radiomics nomogram utilizing CT data for predicting perineural invasion (PNI) and survival in gastric cancer (GC) patients. Materials and MethodsA retrospective analysis of 408 GC patients from two institutions: 288 patients from Institution I were divided 7:3 into a training set (n=203) and a testing set (n=85); 120 patients from Institution II served as an external validation set. Radiomics features were extracted and screened from CT images. Independent radiomics, clinical, and combined models were constructed to predict PNI. Model discrimination, calibration, clinical utility, and prognostic significance were evaluated using area under the curve (AUC), calibration curves, decision curves analysis, and Kaplan-Meier curves, respectively. ResultsFifteen radiomics features and three clinical factors were included in the final analysis. The AUCs of the radiomics model in the training, testing, and external validation sets were 0.843 (95% CI: 0.788 - 0.897), 0.831 (95% CI: 0.741 - 0.920), and 0.802 (95% CI: 0.722 - 0.882), respectively. A nomogram was developed by integrating significant clinical factors with radiomics features. The AUCs of the nomogram in the training, testing, and external validation sets were 0.872 (95% CI: 0.823 - 0.921), 0.862 (95% CI: 0.780 - 0.944), and 0.837 (95% CI: 0.767 - 0.908), respectively. Survival analysis revealed that the nomogram could effectively stratify patients for recurrence-free survival (Hazard Ratio: 4.329; 95% CI: 3.159 - 5.934; P<0.001). ConclusionsThe radiomics-derived nomogram presented a promising tool for predicting PNI in GC and held significant prognostic implications. Important FindingsThe nomogram functioned as a non-invasive biomarker for determining the PNI status. The predictive performance of the nomogram surpassed that of the clinical model (P < 0.05). Furthermore, patients in the high-risk group stratified by the nomogram had a significantly shorter RFS (P < 0.05).