The progress and future prospects of the application of circulating tumor DNA in the diagnosis and treatment of gastric cancer

Gastric cancer is a prevalent malignant neoplasm globally, characterized by insidious onset, lack of specific clinical manifestations, and a tendency for patients to present at advanced stages with poor prognosis. Therefore, the quest for highly specific and sensitive biomarkers to assist in diagnosis, guide treatment, and predict prognosis holds paramount significance. Circulating tumor DNA (ctDNA), consisting of cell-free DNA fragments released by tumor cells into the plasma, carries tumor-specific genetic features and epigenetic alterations. In comparison to conventional tissue biopsies, ctDNA offers numerous advantages. It enables the capture of tumor genomic profiles from minimally invasive blood samples, overcomes tumor heterogeneity, and allows for dynamic monitoring of treatment response and prediction of recurrence risk. In the realm of early diagnosis, researchers have developed a detection method called CancerSEEK by combining peripheral blood ctDNA mutations with protein markers, achieving a sensitivity of over 69% in the early detection of gastric, esophageal and pancreatic cancers. Another study utilized a combined detection of 153 methylated DNA sites to diagnose stage Ⅰ, Ⅱ, and Ⅲ gastric cancer with sensitivities of 44%, 59% and 78%, respectively, and a specificity of 92%. Regarding treatment guidance, ctDNA testing facilitates the selection of gastric cancer patients who may benefit from targeted therapies against human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor 2 (FGFR 2) and epidermal growth factor receptor (EGFR). Furthermore, immunotherapy in combination with chemotherapy has become the standard treatment regimen for advanced gastric cancer. Evaluating microsatellite status, tumor mutation burden and EB virus-associated gastric cancer through ctDNA analysis can predict the efficacy of immunotherapy. However, specific gene mutations such as TGFBR2, RHOA and PREX2 indicate a poor response to immunotherapy. For gastric cancer patients undergoing neoadjuvant or palliative chemotherapy, the dynamic changes in ctDNA copy number instability, copy number variation and mutation allele frequency load during chemotherapy significantly correlate with treatment efficacy. Dynamic monitoring through ctDNA analysis is beneficial for timely adjustment of treatment strategies before imaging changes occur. In the realm of predicting recurrence and prognosis, research has shown that minimal residual disease (MRD) may be the primary cause of post-treatment relapse in patients with locally advanced cancer, which has been confirmed through follow-up studies in breast, lung and colorectal cancers. The utilization of ctDNA testing to detect postoperative MRD in gastric cancer has revealed that ctDNA positivity at any time point during follow-up is associated with an increased risk of recurrence. Furthermore, patients with ctDNA-positive results experience shorter disease-free survival and overall survival, with a median lead time of 4.5 to 6.0 months compared to radiographic recurrence. Additionally, ctDNA analysis has shown correlations between TP53 mutations, MET amplification, THBS1 and TIMP-3 methylation, and tumor progression or peritoneal metastasis, indicating similarly poor prognosis. Despite the tremendous potential of ctDNA as a minimally invasive biomarker for tumor screening and monitoring, its application in gastric cancer still faces certain limitations and challenges. This article provided a comprehensive review of the current status and prospects of ctDNA in the field of gastric cancer.

Fine-Grained Emotion Analysis Based on Mixed Model for Product Review

Nowadays, with the rapid development of B2C e-commerce and the popularity of online shopping, the Web storages huge number of product reviews comment by customers. A large number of reviews made it difficult for manufacturers or potential customers to track the comments and suggestions that customers made. This paper presents a method for extracting emotional elements containing emotional objects and emotional words and their tendencies from product reviews based on mixed model. First we constructed conditional random fields to extract emotional elements, lead-in semantic and word meaning as features to improve the robustness of feature template and used rules for hierarchical filtering errors. Then we constructed support vector machine to classify the emotional tendency of the fine-grained elements to achieve key information from product reviews. Deep semantic information imported based on neural network to improve the traditional bag of word model. Experimental results show that the proposed model with deep features efficiently improved the F-Measure

Effects of Serum Lipids on the Long-Term Prognosis of Ampullary Adenocarcinoma Patients after Curative Pancreatoduodenectomy

Background: Serum lipids (SLs), the prominent indicators of lipid metabolism, produce an intricate impact on proliferation, invasion, and metastasis of cancer cells. However, the effects of serum lipids on the prognosis of ampullary adenocarcinoma (AC) have not been investigated. Methods: Patients with AC in the National Cancer Center of China between January 1998 and December 2020 were retrospectively reviewed. Survival analysis for overall survival (OS, Time from operation to death) and recurrence-free survival (RFS, Time from operation to first-time recurrence) was performed using Kaplan–Meier analysis and Cox proportional hazards models. Results: A total of 232 AC patients were enrolled into the study. SLs levels were significantly lower in patients with vascular invasion compared to those without (all p p = 0.015), whereas no statistical significance existed in the analysis of HDL-C, TC, and TG. Conclusions: High levels of preoperative LDL-C is a significant predictor of prolonged prognosis in AC patients, which was also observed to be a protective factor to reduce vascular invasion

Does Surgical Resection Significantly Prolong the Long-Term Survival of Patients with Oligometastatic Pancreatic Ductal Adenocarcinoma? A Cross-Sectional Study Based on 18 Registries

Background: Pancreatic ductal adenocarcinoma (PDAC) is a type of lethal gastrointestinal malignancy. It is mainly discovered at, and diagnosed with, an advanced stage of metastasis. As the only potentially curative treatment for PDAC, surgical resection has an uncertain impact on the survival of these patients. As such, we aimed to investigate if patients with metastatic PDAC (mPDAC) benefit from surgery. Methods: Patients with pancreatic cancer in 18 registries of the Surveillance, Epidemiology, and End Results database between 2000 and 2018 were reviewed retrospectively. According to the American Joint Committee on Cancer (AJCC), the eighth edition staging system was utilized. Propensity score matching was applied to strengthen the comparability of the study. The impact of surgery on survival was evaluated by restricted mean survival time (RMST) and Kaplan–Meier analysis. Results: A total of 210 well-matched mPDAC patients were included in the study. The 1 year, 3 year, and 5 year overall survival (OS) of patients undergoing surgery was 34.3%, 15.2%, and 11.0%, respectively. The 1 year, 3 year, and 5 year cancer-specific survival (CSS) of these patients was 36.1%, 19.7%, and 14.2%, respectively. RMST analysis revealed that mPDAC patients with surgery had better OS and CSS than those without (OS: 9.49 months vs. 6.45 months, p p p p < 0.001). Lastly, a nomogram was established to predict whether an individual was suitable for surgical treatment in this study. Conclusions: Surgical resection significantly prolonged the long-term prognosis of oligometastatic PDAC patients. Such insights might broaden the management of patients with mPDAC to a large extent. However, a prospective clinical trial should be conducted before a recommendation of surgery in these patients

Impact of Diabetes on Short-Term and Long-Term Outcomes of Ampullary Adenocarcinoma Patients after Curative Pancreatoduodenectomy

Background: Many studies have confirmed that diabetes was associated with prognosis in many malignant cancer types. However, the impact of diabetes on ampullary carcinoma (AC) has not been investigated. Methods: A total of 266 AC patients in the National Cancer Center of China between January 1998 and December 2020 were retrospectively reviewed. The postoperative complication rate, postoperative recurrence rate, and long-term survival were compared between the diabetes group and the no diabetes group. Results: A total of 32 AC patients (12.03%) were diagnosed with diabetes before surgery. In total, 111 patients (41.73%) had one or more postoperative complications, and there was no perioperative death. There was no statistically significant difference regarding postoperative complications between the diabetes group and the no diabetes group. Altogether, 120 patients (45.11%) experienced postoperative recurrence. Multivariate analysis revealed that diabetes was an independent risk factor for the recurrence (OR: 2.384, 95% CI: 1.065&ndash;5.336, p = 0.035), OS (HR: 1.597, 95% CI: 1.005&ndash;2.537, p = 0.047), and RFS (HR: 1.768, 95% CI: 1.068&ndash;2.925, p = 0.027) in AC patients after curative pancreatoduodenectomy. Conclusions: Diabetes may adversely affect the recurrence of patients with AC after curative pancreaticoduodenectomy, leading to an increased risk of poor prognosis in early-stage patients. Further studies involving a large sample size are needed to validate our results

Genome-Wide Analysis Reveals Dynamic Epigenomic Differences in Soybean Response to Low-Phosphorus Stress

Low-phosphorus (low-P) stress has a significant limiting effect on crop yield and quality. Although the molecular mechanisms of the transcriptional level responsible for the low-P stress response have been studied in detail, the underlying epigenetic mechanisms in gene regulation remain largely unknown. In this study, we evaluated the changes in DNA methylation, gene expression and small interfering RNAs (siRNAs) abundance genome-wide in response to low-P stress in two representative soybean genotypes with different P-efficiencies. The DNA methylation levels were slightly higher under low-P stress in both genotypes. Integrative methylation and transcription analysis suggested a complex regulatory relationship between DNA methylation and gene expression that may be associated with the type, region, and extent of methylation. Association analysis of low-P-induced differential methylation and gene expression showed that transcriptional alterations of a small part of genes were associated with methylation changes. Dynamic methylation alterations in transposable element (TE) regions in the CHH methylation context correspond with changes in the amount of siRNA under low-P conditions, indicating an important role of siRNAs in modulating TE activity by guiding CHH methylation in TE regions. Together, these results could help to elucidate the epigenetic regulation mechanisms governing the responses of plants to abiotic stresses

Equivalent Survival between Gastric Large-Cell Neuroendocrine Carcinoma and Gastric Small-Cell Neuroendocrine Carcinoma

Background: According to the 2019 World Health Organization (WHO) classification of gastric neuroendocrine neoplasms, gastric neuroendocrine carcinoma (GNEC) can be further divided into gastric large-cell neuroendocrine carcinoma (GLNEC) and gastric small-cell neuroendocrine carcinoma (GSNEC). Whether the prognoses of the two types have a discrepancy has long been disputed. Method: We collected patients diagnosed with GLNEC or GSNEC in the National Cancer Center of China between January 2000 and December 2020. The characteristics and survival outcomes were compared between the two groups. We further verified our conclusion using the SEER dataset. Results: A total of 114 GNEC patients, including 82 patients with GLNEC and 32 patients with GSNEC, have completed treatment in our hospital. Clinicopathologic differences were not observed between patients with GSNEC and GLNEC concerning the sex, age, body mass index, Charlson Comorbidity Index, tumor location, tumor size, stage, treatment received, the expression of neuroendocrine markers (CD56, Chromogranin A, synaptophysin), and score on the Ki-67 index. The 1-year, 3-year, and 5-year overall survival rates of GLNEC and GSNEC were 89.0%, 60.5%, and 52.4%, and 93.8%, 56.3%, and 52.7%, which showed no statistically significant differences. This result was confirmed further by using the SEER dataset after the inverse probability of treatment weighting. Conclusions: Although with different cell morphology, the comparison of prognosis between the GLNEC and GSNEC has no significant statistical difference

Transcriptome-wide identification of novel circular RNAs in soybean in response to low-phosphorus stress.

Low-phosphorus (LP) stress is a major factor limiting the growth and yield of soybean. Circular RNAs (circRNAs) are novel noncoding RNAs that play a crucial role in plant responses to abiotic stress. However, how LP stress mediates the biogenesis of circRNAs in soybean remains unclear. Here, to explore the response mechanisms of circRNAs to LP stress, the roots of two representative soybean genotypes with different P-use efficiency, Bogao (a LP-sensitive genotype) and Nannong 94156 (a LP-tolerant genotype), were used for the construction of RNA sequencing (RNA-seq) libraries and circRNA identification. In total, 371 novel circRNA candidates, including 120 significantly differentially expressed (DE) circRNAs, were identified across different P levels and genotypes. More DE circRNAs were significantly regulated by LP stress in Bogao than in NN94156, suggesting that the tolerant genotype was less affected by LP stress than the sensitive genotype was; in other words, NN94156 may have a better ability to maintain P homeostasis under LP stress. Moreover, a positive correlation was observed between the expression patterns of P stress-induced circRNAs and their circRNA-host genes. Gene Ontology (GO) enrichment analysis of these circRNA-host genes and microRNA (miRNA)-targeted genes indicated that these DE circRNAs were involved mainly in defense responses, ADP binding, nucleoside binding, organic substance catabolic processes, oxidoreductase activity, and signal transduction. Together, our results revealed that LP stress can significantly alter the genome-wide profiles of circRNAs and indicated that the regulation of circRNAs was both genotype and environment specific in response to LP stress. LP-induced circRNAs might provide a rich resource for LP-responsive circRNA candidates for future studies