The incidence of gastric cancer is high in Chinese Tibetan. This study aimed to identify the differentially expressed microRNAs (miRNAs) and further explore their potential roles in Tibetan with gastric cancer so as to predict potential therapeutic targets. A total of 10 Tibetan patients (male:female = 6:4) with gastric cancer were enrolled for isolation of matched gastric cancer and adjacent non-cancerous tissue samples. Affymetrix GeneChip microRNA 3.0 Array was employed for detection of miRNA expression in samples. Differential expression analysis between two sample groups was analyzed using Limma package. Then, MultiMiR package was used to predict targets for miRNAs. Following, the target genes were put into DAVID (Database for Annotation, Visualization and Integrated Discovery) to identify the significant pathways of miRNAs. Using Limma package in R, a total of 27 differentially expressed miRNAs were screened out in gastric cancer, including 25 down-regulated (e.g. hsa-miR-148a-3p, hsa-miR-148b-3p and hsa-miR-363-3p) and 2 up-regulated miRNAs. According to multiMiR package, a number of 1445 target genes (e.g. Wnt1, KLF4 and S1PR1) of 13 differentially expressed miRNAs were screened out. Among those miRNAs, hsa-miR-148a-3p, hsa-miR-148b-3p and hsa-miR-363-3p were identified with the most target genes. Furthermore, three miRNAs were significantly enriched in numerous common cancer-related pathways, including “Wnt signaling pathway”, “MAPK signaling pathway” and “Jak-STAT signaling pathway”. The present study identified a downregulation and enrichment in cancer-related pathways of hsa-miR-148a-3p, hsa-miR-148b-3p and hsa-miR-363-3p in Tibetan with gastric cancer, which can be suggested as therapeutic targets.

Gastric cancer (GC) is a deadly disease with poor prognosis and few treatment options. Tropomyosin 4 (TPM4) is an actin-binding protein that stabilizes the cytoskeleton of cells and has an unclear role in GC. This study aimed to elucidate the role and underlying mechanisms of TPM4 in GC pathogenesis. The expression and diagnostic and prognostic value of TPM4 in GC were analyzed using bioinformatics. A nomogram based on TPM4 expression was created and validated with an external cohort. TPM4-knockdown GC cells and xenograft models in nude mice were used to study the function of TPM4 in vitro and in vivo. Proteomic and rescue experiments confirmed the regulatory effect of TPM4 on stearoyl-CoA desaturase 1 (SCD1) in GC. Immunohistochemistry verified the expression and correlation of the TPM4 and SCD1 proteins in GC tissues. Our study identified TPM4 as an oncogene in GC, suggesting its potential diagnostic and prognostic value. The TPM4-based nomogram showed potential prognostic value for clinical use. TPM4 knockdown inhibited GC cell proliferation, induced ferroptosis, and slowed tumor growth in vivo, which is achieved by inhibiting SCD1 expression. Immunohistochemical analysis of GC tissues revealed elevated expression levels of both TPM4 and SCD1 proteins, with a positive correlation observed between their expression. TPM4 is a promising target for new diagnostic, prognostic, and therapeutic strategies for GC. Downregulation of TPM4 inhibits GC cell growth and induces ferroptosis by suppressing SCD1 expression. Graphical abstract Our study shows that inhibiting TPM4 expression significantly hinders GC cell proliferation and triggers ferroptosis, with SCD1 likely acting as a downstream target. Inhibiting SCD1 enhances sensitivity to ferroptosis by altering the SFA/MUFA ratio and induces apoptosis by initiating ER stress and UPR activation. This study suggests that the downregulation of TPM4 can inhibit the proliferation of GC cells and induce ferroptosis and apoptosis by suppressing SCD1 expression.

Rhodiola algida var. tangutica is a traditional Tibetan herb. Its root and rhizome have been successfully used as an effective clinical remedy for the prevention and treatment of cancer and high-altitude sickness. This study aimed to investigate the effect of Rhodiola algida var. tangutica on hypoxic MCF-7 breast cancer cells and the underlying mechanisms. The antiproliferative effects of R. algida on MCF-7 breast cancer cells were compared in vitro under hypoxic and normal conditions by using MTT analysis. The influence of R. algida on cancer cell apoptosis was determined by flow cytometry. The expression levels of hypoxia-inducible factor (HIF)-1α and HIF-2α were evaluated by western blot analysis. R. algida inhibited the proliferation of MCF-7 breast cancer cells in a dose- and time-dependent manner. The results of flow cytometry indicated that the antiproliferative effect of R. algida was mediated by apoptosis induction. Pretreatment with R. algida significantly suppressed the hypoxia-induced proliferation and expression of HIF-1α and HIF-2α in MCF-7 breast cancer cells. R. algida might exert an anti-carcinogenic effect on MCF-7 breast cancer cells by decreasing the protein levels of HIF-1α and HIF-2α, which are overexpressed under hypoxic conditions. This effect might be elicited by inhibiting the hypoxia-induced proliferation of MCF-7 breast cancer cells.

Objective. To study the expression and clinical importance of CD4⁺T, CD8⁺T cells, and CD4⁺T/CD8⁺T cell percentage in gastric cancer (GC) patients. Methods. The blood count of CD4⁺T and CD8⁺T lymphocytes was ascertained via flow cytometry before surgery in 93 GC patients undergoing gastrectomy. The CD4⁺T, CD8⁺T, and Foxp3⁺T lymphocytes in cancerous and normal adjacent tissues and the presence of PD-L1 in cancerous tissues were detected via immunohistochemistry. The link between the permeation of CD4⁺T, CD8⁺T lymphocytes in venous blood, and cancer and normal adjacent tissues was analyzed. Results. Lauren histotype, TNM stage, lymphatic/nervous invasion, and NLR level were all considerably associated with peripheral CD4⁺T and CD8⁺T cell levels, whereas CD8⁺T lymphocytes were also associated with vascular invasion ( ). The CD4⁺T lymphocyte counts, CD4⁺T, and CD8⁺T cell percentage in GC tissues were found to have been decreased when compared to normal adjacent tissues, whereas the CD8⁺T and Foxp3⁺T lymphocyte count was higher in GC tissues ( ). According to a Spearman analysis, the CD4⁺T and CD8⁺T cell counts in tumor tissues were positively related to the Foxp3⁺T lymphocyte count ( ). Greater peripheral CD4⁺T lymphocyte counts and increased level of CD4⁺T/CD8⁺T percentage corresponded with greater CD4⁺T cell levels and increased CD4⁺T/CD8⁺T quantity in normal adjacent tissues. Higher levels of peripheral CD8⁺T cells corresponded with higher quantities of CD8⁺T cells in cancer tissues. A reduced CD4⁺T lymphocyte count, together with a reduced CD4⁺T/CD8⁺T percentage in venous blood, was consistent with a diminished CD4⁺T cell count along with a reduced CD4⁺T/CD8⁺T lymphocyte ratio in cancer and normal adjacent tissues. Conclusion. The peripheral quantity of CD4⁺T and CD8⁺T lymphocytes in GC patients can partly reflect the infiltrating state of these lymphocytes in cancer and normal adjacent tissues and can preliminarily predict immunotherapy response to a certain extent.

As previously reported (ASCO 2020), PCA titration provides faster analgesic effect and higher patient satisfaction than non-PCA for severe cancer pain; however, optimal analgesic maintenance after the successful titration was unknown.