Gastric cancer with brain metastasis: from molecular characteristics and treatment.

Gastric cancer is one of the cancers with increasing incidence and ranks fourth globally among the most frequent causes of cancer-related mortality. Early gastric cancer is often asymptomatic or presents with atypical symptoms, and the majority of patients present with advanced disease upon diagnosis. Brain metastases are present in approximately 1% of gastric cancer patients at the time of diagnosis, which significantly contributed to the overall mortality of the disease worldwide. Conventional therapies for patients with brain metastases remain limited and the median overall survival of patients is only 8 months in advanced cases. Recent studies have improved our understanding of the molecular mechanisms underlying gastric cancer brain metastases, and immunotherapy has become an important treatment option in combination with radiotherapy, chemotherapy, targeted therapy and surgery. This review aims to provide insight into the cellular processes involved in gastric cancer brain metastases, discuss diagnostic approaches, evaluate the integration of immune checkpoint inhibitors into treatment and prognosis, and explore the predictive value of biomarkers in immunotherapy.

Identification of prognosis-related lncRNAs and cell validation in lung squamous cell carcinoma based on TCGA data.

Objective: To discern long non-coding RNAs (lncRNAs) with prognostic relevance in the context of lung squamous cell carcinoma (LUSC), we intend to predict target genes by leveraging The Cancer Genome Atlas (TCGA) repository. Subsequently, we aim to investigate the proliferative potential of critical lncRNAs within the LUSC milieu. Methods: DESeq2 was employed to identify differentially expressed genes within the TCGA database. Following this, we utilized both univariate and multivariate Cox regression analyses to identify lncRNAs with prognostic relevance. Noteworthy lncRNAs were selected for validation in cell lines. The intracellular localization of these lncRNAs was ascertained through nucleocytoplasmic isolation experiments. Additionally, the impact of these lncRNAs on cellular proliferation, invasion, and migration capabilities was investigated using an Antisense oligonucleotides (ASO) knockdown system. Results: Multivariate Cox regression identified a total of 12 candidate genes, consisting of seven downregulated lncRNAs (BRE-AS1, CCL15-CCL14, DNMBP-AS1, LINC00482, LOC100129034, MIR22HG, PRR26) and five upregulated lncRNAs (FAM83A-AS1, LINC00628, LINC00923, LINC01341, LOC100130691). The target genes associated with these lncRNAs exhibit significant enrichment within diverse biological pathways, including metabolic processes, cancer pathways, MAPK signaling, PI3K-Akt signaling, protein binding, cellular components, cellular transformation, and other functional categories. Furthermore, nucleocytoplasmic fractionation experiments demonstrated that LINC00923 and LINC01341 are predominantly localized within the cellular nucleus. Subsequent investigations utilizing CCK-8 assays and colony formation assays revealed that the knockdown of LINC00923 and LINC01341 effectively suppressed the proliferation of H226 and H1703 cells. Additionally, transwell assays showed that knockdown of LINC00923 and LINC01341 significantly attenuated the invasive and migratory capacities of H226 and H1703 cells. Conclusion: This study has identified 12 candidate lncRNA associated with prognostic implications, among which LINC00923 and LINC01341 exhibit potential as markers for the prediction of LUSC outcomes.

Platelet count and gastric cancer susceptibility: A Mendelian randomization study.

The objective of this study was to ascertain the potential causal linkage between platelet (PLT) counts and the incidence of gastric cancer (GC). This study employed a 2-sample Mendelian randomization (MR) approach, utilizing the inverse variance weighting, weighted median, and MR-Egger regression methodologies. The publicly accessible summary statistics dataset from the genome-wide association study pertaining to individuals of European ancestry (n = 145,648) was employed as the foundational resource for the exposure variable. Concomitantly, the non-cancer disease codes for GC (n = 6563), derived from individuals within the UK Biosample Bank, were utilized as the outcome measure. A set of 132 single-nucleotide polymorphisms exhibiting genome-wide significance were selected as instrumental variables, drawn from the genome-wide association studies focused on PLT counts. The application of the weighted median methodology yielded indications suggesting the possible absence of a causal relationship between PLT counts and GC (beta = 0.139, SE = 0.079, P = .077). Contrarily, the implementation of the inverse variance weighting technique produced results indicative of a potential causal relationship between PLT counts and GC (beta = 0.128, SE = 0.049, P = .009). The assessment of Cochran Q test and the scrutiny of funnel plots unveiled no discernible indications of heterogeneity or asymmetry, thus signifying the absence of directional pleiotropy. The outcomes derived from the MR analysis lend credence to the hypothesis that there exists a plausible causal relationship between erythrocyte pressure and an elevated susceptibility to gastric cancer.

Development and Validation of the Oxidative Stress Related lncRNAs for Prognosis in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell cancer (ESCC) is an aggressive disease associated with a poor prognosis. Long non-coding RNAs (lncRNAs) and oxidative stress play crucial roles in tumor progression. We aimed to identify an oxidative stress-related lncRNA signature that could predict the prognosis in ESCC. In the GSE53625 dataset, we identified 332 differentially expressed lncRNAs (DElncRNAs) between ESCC and control samples, out of which 174 were oxidative stress-related DElncRNAs. Subsequently, seven oxidative stress-related DElncRNAs (CCR5AS, LINC01749, PCDH9-AS1, TMEM220-AS1, KCNMA1-AS1, SNHG1, LINC01672) were selected based on univariate and LASSO Cox to build a prognostic risk model, and their expression was detected by RT-qPCR. The model exhibited an excellent ability for the prediction of overall survival (OS) and other clinicopathological traits using Kaplan-Meier (K-M) survival curves, receiver operating characteristic (ROC) curves, and the Wilcoxon test. Additionally, analysis of infiltrated immune cells and immune checkpoints indicated differences in immune status between the two risk groups. Finally, the in vitro experiments showed that PCDH9-AS1 overexpression inhibited proliferation ability and promoted apoptosis and oxidative stress levels in ESCC cells. In conclusion, our study demonstrated that a novel oxidative stress-related DElncRNA prognostic model performed favorably in predicting ESCC patient prognosis and benefits personalized clinical applications.

Antibody-drug conjugates: the clinical development in gastric cancer.

Gastric cancer (GC) is a prevalent malignant tumor of the digestive system worldwide, ranking among the top five in terms of incidence and mortality. However, the clinical efficacy of conventional treatments for gastric cancer remains limited, with a median overall survival of approximately eight months for advanced cases. In recent years, researchers have increasingly focused on antibody-drug conjugates (ADCs) as a promising approach. ADCs are potent chemical drugs that selectively target cancer cells by binding to specific cell surface receptors with antibodies. Notably, ADCs have demonstrated promising results in clinical studies and have made significant strides in the treatment of gastric cancer. Currently, several ADCs are under investigation in clinical trials for gastric cancer patients, targeting various receptors such as EGFR, HER-2, HER-3, CLDN18.2, Mucin 1, among others. This review offers a comprehensive exploration of ADC drug characteristics and provides an overview of the research progress in ADC-based therapies for gastric cancer.