The minimum number of examined lymph nodes was 24 for optimal survival of pathological T2-4 gastric cancer: a multi-center, hospital-based study covering 20 years of data.

INTRODUCTION: The current National Comprehensive Cancer Network (NCCN) guidelines recommend that at least 16 lymph nodes should be examined for gastric cancer patients to reduce staging migration. However, there is still debate regarding the optimal management of examined lymph nodes (ELNs) for gastric cancer patients. In this study, we aimed to develop and test the minimum number of ELNs that should be retrieved during gastrectomy for optimal survival in patients with gastric cancer. METHODS: We used the restricted cubic spline (RCS) to identify the optimal threshold of ELNs that should be retrieved during gastrectomy based on the China National Cancer Center Gastric Cancer (NCCGC) database. Northwest cohort, which sourced from the highest gastric cancer incidence areas in China, was used to verify the optimal cutoff value. Survival analysis was performed via Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: In this study, 12,670 gastrectomy patients were included in the NCCGC cohort and 4941 patients in the Northwest cohort. During 1999-2019, the average number of ELNs increased from 17.88 to 34.45 nodes in the NCCGC cohort, while the number of positive lymph nodes remained stable (5-6 nodes). The RCS model showed a U-curved association between ELNs and the risk of all-cause mortality, and the optimal threshold of ELNs was 24 [Hazard ratio (HR) = 1.00]. The ELN ≥ 24 group had a better overall survival (OS) than the ELN < 24 group clearly (P = 0.003), however, with respect to the threshold of 16 ELNs, there was no significantly difference between the two groups (P = 0.101). In the multivariate analysis, ELN ≥ 24 group was associated with improved survival outcomes in total gastrectomy patients [HR = 0.787, 95% confidence interval (CI): 0.711-0.870, P < 0.001], as well as the subgroup analysis of T2 patients (HR = 0.621, 95%CI: 0.399-0.966, P = 0.035), T3 patients (HR = 0.787, 95%CI: 0.659-0.940, P = 0.008) and T4 patients (HR = 0.775, 95%CI: 0.675-0.888, P < 0.001). CONCLUSION: In conclusion, the minimum number of ELNs for optimal survival of gastric cancer with pathological T2-4 was 24.

Phosphoproteomic analysis of the antitumor effects of ginsenoside Rg3 in human breast cancer cells.

The incidence of breast cancer has been increasing in China and the age of breast cancer onset is earlier compared with Western countries. Compounds commonly used in Traditional Chinese Medicine (TCM) are an important source of anticancer drugs. Ginseng is one of the most common medicines used in TCM. Ginsenosides, which are saponins found in the ginseng plant, are the major active components responsible for the chemopreventive effects of ginseng in cancer. However, the mechanisms by which ginsenosides exert their anticancer effects remain elusive. The current study combined tandem mass tag (TMT)-based quantification with titanium dioxide-based phosphopeptide enrichment to quantitatively analyze the changes in phosphoproteomes in breast cancer MDA-MB-231 cells that occur following treatment with the ginsenoside Rg3. A total of 5,140 phosphorylation sites on 2,041 phosphoproteins were quantified and it was demonstrated that the phosphorylation status of 13 sites were altered in MDA-MB-231 cells following treatment with Rg3. The perturbed phosphoproteins were: Cleavage and polyadenylation specificity factor subunit 7, elongation factor 2 (EEF2), HIRA-interacting protein 3, melanoma-associated antigen D2, myosin phosphatase Rho-interacting protein, probable E3 ubiquitin-protein ligase MYCBP2, PRKC apoptosis WT1 regulator protein, protein phosphatase 1 regulatory subunit 12A, E3 SUMO-protein ligase RanBP2, Septin-9, thymopoietin, and E3 UFM1-protein ligase 1. Western blotting confirmed that Rg3 increased the phosphorylation of EEF2 on Thr57 but did not alter the protein expression of EEF2 in MDA-MB-231 and HCC1143 cells. These ginsenoside Rg3-regulated proteins are involved in various biological processes, including protein synthesis, cell division and the inhibition of nuclear factor-κB signaling. The results of the present study revealed that Rg3 exerts its anticancer effects via a combination of different signaling pathways.