Plasma circulating tumor DNA unveils the efficacy of PD-1 inhibitors and chemotherapy in advanced gastric cancer.

Programmed Death Receptor 1 (PD-1) inhibitors, when combined with chemotherapy, have exhibited notable effectiveness in enhancing the survival outcomes of patients afflicted with advanced gastric cancer. However, it is important to acknowledge that not all patients derive substantial benefits from this therapeutic approach, highlighting the crucial necessity of identifying efficacious biomarkers to inform immunotherapy interventions. In this study, we sought to investigate the predictive utility of circulating tumor DNA (ctDNA) as a biomarker in a cohort of 30 patients diagnosed with advanced gastric cancer, all of whom underwent first-line treatment involving PD-1 inhibitor administration alongside chemotherapy. We procured peripheral blood samples both at baseline and following the completion of two treatment cycles. Additionally, baseline tissue specimens were collected for the purpose of genomic alteration assessment, employing both 47-gene and 737-gene next-generation sequencing panels for plasma and tumor tissue, respectively. We delineated a ctDNA response as the eradication of maximum variant allele frequencies relative to baseline levels. Notably, the objective response rate among individuals exhibiting a ctDNA response proved significantly superior in comparison to non-responders (P = 0.0073). Furthermore, patients who manifested a ctDNA response experienced markedly prolonged progression-free survival (PFS) and overall survival (OS) when juxtaposed with those devoid of a ctDNA response (median PFS: 15.6 vs. 6.0 months, P = 0.003; median OS: not reached [NR] vs. 9.0 months, P = 0.011). In summation, patients with advanced gastric cancer receiving first-line treatment with PD-1 inhibitors and chemotherapy, dynamic changes in ctDNA can serve as a potential biomarker for predicting treatment efficacy and long-term outcomes.

CircRPPH1 promotes the stemness of gastric cancer cells by targeting miR-375/SLC7A11 axis.

This study mainly focuses on revealing the role of circRPPH1 in gastric cancer cell stemness. In vitro and in vivo experiments were performed to evaluate the effects of circRPPH1 on gastric cancer cell stemness. Luciferase reporter and RIP assays were implemented to reveal the underlying mechanisms. MiR-375 directly bound to circRPPH1 in gastric cancer cells. And circRPPH1 acted as an miR-375 sponge to positively regulate SLC7A11 expression, which has been confirmed to be the direct target of miR-375 in gastric cancer, and thus regulated ferroptosis. Moreover, circRPPH1 promoted the stemness of gastric cancer cells dependent on the miR-375/SLC7A11. This study provides a potential target for gastric cancer progression based on the circRPPH1/miR-375/SLC7A11 regulatory axis.

CircRNA-Encoded Peptides or Proteins as New Players in Digestive System Neoplasms.

Circular RNAs (circRNAs) were considered non-coding RNAs. Nowadays, a large number of studies have found that these RNAs contain open reading frames that can be translated in a cap-independent manner, such as internal ribosome entry site (IRES) and N6-methyladenosine (m6A). The encoded peptides or proteins affect the occurrence and development of tumors by regulating the Yap-hippo and the Wnt/ß-catenin signaling pathways, as well as the malignant progression of tumors through phosphorylation and ubiquitination of specific molecules. This review will summarize the regulation of circRNA translation and the functional roles and underlying mechanisms of circRNA-derived peptides or proteins in digestive tract tumors. Some circRNA-encoded peptides or proteins may be used as tumor biomarkers and prognostic factors for early screening and treatment of clinical gastrointestinal tumors.

CXCL5: A coachman to drive cancer progression.

Chemokines are a class of pro-inflammatory cytokines that can recruit and activate chemotactic cells. C-X-C motif chemokine ligand 5 (CXCL5) is a member of the chemokine family binding CXCR2 (C-X-C Motif Chemokine Receptor 2), a G-protein coupled receptor. Accumulated evidence has shown that dysregulated CXCL5 participates in tumor metastasis and angiogenesis in human malignant tumors. In this review, we summarized the advances in research on CXCL5, including its dysregulation in different tumors and the mechanism associated with tumor behavior (formation of the immunosuppressive microenvironment, promotion of tumor angiogenesis, and metastasis). We also summarized and discussed the perspective about the potential application of CXCL5 in tumor therapy targeting the tumor inflammatory microenvironment.