Advances in Treatment Models of Advanced Gastric Cancer

Li, Tao; He, Ya‐Ling; Zhong, Qinglei; Yu, Jiang; Chen, Xinhua

doi:10.1177/15330338221090353

Cited by 6 publications

(3 citation statements)

References 87 publications

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“…Studies have reported a 5-year survival rate of > 90% for early-stage GC; however, early diagnosis remains limited, with most patients diagnosed at an advanced stage 16 . Recently, the combination of chemotherapeutic and targeted therapies as first-line therapy for advanced GC has improved clinical efficacy, but the prognosis has not substantially improved 17 . Hence, there is an urgent need to identify specific biomarkers to determine the prognosis of patients with GC.…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of a Cancer-Testis Antigen-Related Signature to Predict the Prognosis in Stomach Adenocarcinoma

Bian,

Cao,

et al. 2024

J. Cancer

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Background: Stomach adenocarcinoma (STAD) is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Cancer-testis antigens (CTAs) participate in the pathogenesis and development of multiple cancers and are aberrantly overexpressed in various types of cancer. This study aimed to develop a CTA-related gene signature (CTARSig) to predict prognosis in STAD patients and explore its underlying mechanisms. Methods: We performed differential and prognostic analyses of CTA-related genes and constructed a CTA-related signature (CTARSig) along with a novel nomogram to predict the prognosis of patients with STAD based on the Cox and The Least Absolute Shrinkage and Selection Operator. CTARSig was further validated in an external cohort (GSE84437). Additionally, univariate and multivariate Cox regression, as well as receiver operating characteristic (ROC) analyses, were performed to assess the CTARSig systematically. Single-sample gene set enrichment analysis and ESTIMATE were used to characterise the Tumor Immune Microenvironment (TIME) in patients with STAD. Furthermore, Gene Set Variation Analysis, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology analyses revealed the biological functions and signalling pathways associated with CTARSig. Finally, the human gastric cancer cell lines, HCG-27 and AGS, were used for in vitro and in vivo experiments, respectively, to further validate the role of ELOVL4. Results: Eleven CTA-related genes were identified to construct the CTARSig. Kaplan-Meier curves, independent prognostic analysis, and ROC curves revealed that CTARSig could better predict survival in patients with STAD. Moreover, in our study, we demonstrated that ELOVL4 is upregulated in gastric cancer tissues and that its high expression is associated with poor survival. Additionally, in vitro and in vivo experiments demonstrated that ELOVL4 promotes the metastatic and invasive potential of STAD cells, suggesting it may be a potential therapeutic target for STAD. Conclusion: In this study, a novel signature associated with CTAs was constructed for STAD, which may be a good predictor of patient prognosis. Thus, ELOVL4 may be a potential therapeutic target for gastric cancer. This study provides new insights into the potential roles of CTAs in gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Identification and Validation of a Cancer-Testis Antigen-Related Signature to Predict the Prognosis in Stomach Adenocarcinoma

Bian,

Cao,

et al. 2024

J. Cancer

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“…Recent studies have shown that the drug sensitivity test on PD‐CRC organoids can predict patient outcomes with 100% sensitivity, 42 , 43 even if some intra‐tumor heterogeneity is lost in the spheroid/organoid line. 44 Our PD–GC‐SC spheroids can be utilized to investigate new molecular targeted therapies and their companion diagnostics for patient selection, 45 , 46 as we recently identified a subset of PD–CRC‐SC spheroid lines that responded to fibroblast growth factor receptor inhibitors. 47 , 48 Additionally, the genomic and expression profiles of GC‐SC spheroids will help determine novel molecular subtypes and diagnostic gene signatures.…”

Section: Discussionmentioning

confidence: 99%

Novel and efficient method for culturing patient‐derived gastric cancer stem cells

et al. 2023

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Experimental techniques for patient-derived cancer stem-cell organoids/spheroids can be powerful diagnostic tools for personalized chemotherapy. However, establishing their cultures from gastric cancer remains challenging due to low culture efficiency and cumbersome methods. To propagate gastric cancer cells as highly proliferative stem-cell spheroids in vitro, we initially used a similar method to that for colorectal cancer stem cells, which, unfortunately, resulted in a low success rate (25%, 18 of 71 cases). We scrutinized the protocol and found that the unsuccessful cases were largely caused by the paucity of cancer stem cells in the sampled tissues as well as insufficient culture media. To overcome these obstacles, we extensively revised our sample collection protocol and culture conditions. We then investigated the following second cohort and, consequently, achieved a significantly higher success rate (88%, 29 of 33 cases). One of the key improvements included new sampling procedures

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“…Although these agents improve treatment outcomes and the overall survival rates of patients with gastric cancer, most patients with advanced-stage cancer are excluded from molecularly targeted treatment and have a poor prognosis, with a 5-year relative survival rate of 6% [ 4 ]. As a result, the development of new targeted drugs to prolong the survival of patients with advanced gastric cancer is a top priority [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

IDF-11774 Induces Cell Cycle Arrest and Apoptosis by Inhibiting HIF-1α in Gastric Cancer

Kim,

Jin

et al. 2023

Pharmaceutics

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Hypoxia-inducible factor-1 alpha (HIF-1α) is a regulatory factor of intracellular oxygen supersession. The expression or increased activity of HIF-1α is closely related to various human cancers. Previously, IDF-11774 was demonstrated to inhibit HSP70 chaperone activity and suppress the accumulation of HIF-1α. In this study, we aimed to determine the effects of IDF-11774 on gastric cancer cell lines. Treatment with IDF-11774 was found to markedly decrease the proliferation, migration, and invasion of the gastric cancer cell lines. Furthermore, the phosphorylation levels of extracellular signal-regulated kinase 1/2, p38, and Jun N-terminal kinase in the mitogen-activated protein kinase signaling pathways were markedly increased in a dose-dependent manner, ultimately promoting apoptosis via the induction of cell cycle arrest. Our findings indicate that HIF-1α inhibitors are potent drugs for the treatment of gastric cancer.

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Advances in Treatment Models of Advanced Gastric Cancer

Cited by 6 publications

References 87 publications

Identification and Validation of a Cancer-Testis Antigen-Related Signature to Predict the Prognosis in Stomach Adenocarcinoma

Identification and Validation of a Cancer-Testis Antigen-Related Signature to Predict the Prognosis in Stomach Adenocarcinoma

Novel and efficient method for culturing patient‐derived gastric cancer stem cells

IDF-11774 Induces Cell Cycle Arrest and Apoptosis by Inhibiting HIF-1α in Gastric Cancer

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