A SEER population analysis of stage IB resected gastric cancer: who can benefit from adjuvant therapy?
IB 期切除胃癌的 SEER 人群分析: 谁能从辅助治疗中获益？
- 作者列表："Wang Y","Guo S","Zhang J","Meng XY","Zheng ZC","Zhao Y
:Objective: The benefit of adjuvant therapy (AT) remains controversial in stage IB gastric cancer (GC). This study aimed to offer a reference for the rational indications of AT.Methods: We retrospectively included 1216 stage IB GC who experienced curative surgery from the SEER database between 2004 and 2015. These patients were allocated into two groups: Group AT and Group surgery alone (Group SA). We established a nomogram to predict OS and then divided whole cohort into low-risk and high-risk groups based on the OS predicted by the nomogram.Results: Six variables, which were significantly related with OS of entire patients after matched, were incorporated in the nomogram. These variables were age, examined lymph nodes, tumor site, marital, family income and stage IB. The C-index of the model was 0.637 and the calibration curve showed that the anticipated values were in accordance with the actual values. The decision curve demonstrated that the optimal clinical impact was achieved when the threshold possibility was 0-56%. Then, the entire cohort was separated into low-risk (≤159 points) as well as high-risk (>159 points) groups based on the projected 5-year OS of recursive partitioning analysis. Group SA revealed a significantly poorer OS than Group AT for high-risk patients (p < .001); on the other hand, there was a comparable OS for low-risk patients (p = .361).Conclusions: We have developed an effective, intuitional and applied prognostic tool to clinical decision-making. For stage IB GC after surgical resection, AT was only recommended for high-risk patients. However, AT may be dispensable for low-risk patients.
目的: IB 期胃癌 (GC) 辅助治疗 (AT) 的获益仍存在争议。本研究旨在为 AT 的合理适应症提供参考。方法: 我们回顾性纳入了 1216 例 IB 期 GC，他们经历了来自 SEER 数据库 2004年和 2015 的治愈性手术。将这些患者分为两组: AT 组和单纯手术组 (SA 组)。我们建立了预测 OS 的列线图，然后根据列线图预测的 OS 将整个队列分为低风险和高风险组。结果: 在匹配后，与整个患者的 OS 显著相关的 6 个变量被纳入列线图。这些变量是年龄、检查的淋巴结、肿瘤部位、婚姻、家庭收入和 IB 期。模型的 C 指数为 0.637，校准曲线显示预期值与实际值一致。决策曲线表明，当阈值可能性为 0-56% 时，达到最佳临床影响。然后，将整个队列分为低风险 (≤ 159 分) 和高风险 (> 159 分) 基于递归分区分析的预计 5 年 OS 进行分组。SA 组显示高危患者的 OS 显著低于 AT 组 (p
METHODS::Diffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that the alter of the cellular cytoskeleton and intercellular adhesion. CD2-associated protein (CD2AP) is one of the critical proteins regulating cytoskeleton assembly and intercellular adhesion. However, no study has investigated the expression and biological significance of CD2AP in gastric cancer (GC) to date. Therefore, the aim of our study was to explore if the expression of CD2AP is associated with any clinical features of GC and to elucidate the underlying mechanism. Immunohistochemistry of 620 patient tissue samples indicated that the expression of CD2AP is downregulated in DGC. Moreover, a low CD2AP level was indicative of poor patient prognosis. In vitro, forced expression of CD2AP caused a significant decrease in the migration and invasion of GC cells, whereas depletion of CD2AP had the opposite effect. Immunofluorescence analysis indicated that CD2AP promoted cellular adhesion and influenced cell cytoskeleton assembly via interaction with the F-actin capping protein CAPZA1. Overall, the upregulation of CD2AP could attenuate GC metastasis, suggesting CD2AP as a novel biomarker for the prognosis and treatment of patients with GC.
METHODS::Aim: To identify the methylated-differentially expressed genes (MDEGs) that may serve as diagnostic markers and therapeutic targets in Epstein-Barr virus-associated gastric cancer (EBVaGC) and to explore the methylation-based pathways for elucidating biological mechanisms of EBVaGC. Materials & methods: Gene expression and methylation profiles were downloaded from GEO database. MDEGs were identified by GEO2R. Pathway enrichment analyses were conducted based on DAVID database. Hub genes were identified by Cytoscape, which were further verified by The Cancer Genome Atlas database. Results: A total of 367 hypermethylated, lowly expressed genes were enriched in specific patterns of cell differentiation. 31 hypomethylated, highly expressed genes demonstrated enrichment in regulation of immune system process. After validation using The Cancer Genome Atlas database, seven genes were confirmed to be significantly different hub genes in EBVaGC. Conclusion: EBVaGC-specific MDEGs and pathways can be served as potential biomarkers for precise diagnosis and treatment of EBVaGC and provide novel insights into the mechanisms involved.
METHODS:Gastric adenocarcinoma, like other cancers, is a multifactorial genetic disease, andmetastasis of cancer cells is one of the main features of this illness. The expressionlevels of the CFL1 gene have been modulated in this pathway. Using small interferingRNA (siRNA) in the treatment of gastric cancer is considered a hopeful genetherapeutic approach. The present study reported the level of CFL1 genes betweentumor and margin and healthy tissue of gastric cancer. Also, the features of a cationicnanoparticle with a polymer coating containing polyacrylic acid and polyethylenei-mine that were used in the delivery of CFL1 siRNA, were shown. Then thecytotoxicity, cellular uptake, and gene silencing efficiency of this nanoparticle wereevaluated with CFL1siRNA. Method:In this study, the CFL1 gene expression was measured in 40 gastricadenocarcinoma, marginal and 15 healthy biopsy samples by a real‐time polymerasechain reaction. Physicochemical characteristics, apoptosis, and inhibition of migrationof the delivery of CFL1 siRNA by nanoparticle and lipofectamine were investigated ingastric cancer cells. Result:The CFL1 expression was remarkably increased in gastric cancer tissues incomparison with the marginal samples and normal tissues (p< .05) and the biomarkerindex for CFL1 was obtained as 0.94, then this gene can be probably used as abiomarker for gastric cancer. After treatment of the AGS cell line by CFL1 siRNA, theCFL1 expression level of mRNA and migration in AGS cells were remarkablysuppressed after transfection. Furthermore, the amount of apoptosis increased(p< .05). Conclusion:Our results demonstrated that CFL1 downregulation in AGS cells caninterdict cell migration. Finally, our outcomes propose that CFL1 can function as anoncogenic gene in gastric cancer and would be considered as a potential purpose ofgene therapy for gastric cancer treatment