RESUMO
Background: Ras-related C3 botulinum toxin substrate 1 (RAC1) is an important member of the Rho GTPase family involved in tumorigenesis. However, its role and potential clinical utility across cancer entities in solid tumors is unknown. Methods: We analyzed data from various databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project, cBioPortal, Tumor Immune Estimation Resource 2 (TIMER2), and published articles. A prognostic nomogram for liver hepatocellular carcinoma (LIHC) patients was developed based on RAC1-guanosine triphosphate (GTP) gene expression levels, which were validated using immunohistochemistry (IHC). Results: In this study, RAC1 was highly expressed in most cancers and correlated with prognosis and pathological stages. Furthermore, significant associations were observed between RAC1 and DNA methylation, immune cell infiltration, immune-related genes, tumor mutational burden, and microsatellite instability in most tumors. As a use case, we employed gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) to analyze the biologic importance of RAC1 expression and established a prognostic nomogram based on tumor stage and RAC1 expression, which can better predict the overall survival rate of patients with LIHC better than tumor stage alone. The gene expression results were validated with IHC, which confirmed a higher expression of the RAC1-GTP protein in LIHC compared to paracancerous tissues. Conclusions: This extensive solid tumor analysis provides sound evidence that RAC1 can serve as both as an immunotherapy target and as a diagnostic and prognostic biomarker.
RESUMO
Background: Gastrointestinal (GI) cancer is the most frequent kind of cancer to involve the retroperitoneal lymph nodes (RPLNs). Radiotherapy (RT) is common treatment of RPLN metastases in patients with GI cancer, while RT is local. Meanwhile, most patients have extra-retroperitoneal metastases. Immunotherapy plus RT have showed effective in advanced non-small cell lung cancer. However, whether the combination therapy is effective on GI cancer with RPLN metastases. In our study, we would estimate the effect of programmed death-1 (PD-1) inhibition in association with intensity modulated radiation therapy (IMRT). Methods: Metastatic GI cancer patients with RPLN who were treated at a single institution were retrospectively evaluated from October 2016 to April 2023, who all had measurable lesion and received any therapy of PD-1 inhibitors alone, IMRT alone or PD-1 inhibitors plus IMRT. The follow-ups were assessed by abdominal computed tomography (CT) every 2 or 3 months to progression, dose-limiting toxicity or death. Results: Among the 98 patients, 46 were treated by PD-1 inhibitors combined with IMRT, 26 were by PD-1 inhibitors only and 26 were by IMRT only. Of those, the median age 62 years (range, 25-84 years). Median progression-free survival (PFS) was 7.5 months and median overall survival (OS) was 10.8 months across the 3 therapy groups. Univariate analysis (UVA) indicated that therapy method (P=0.032) and tumor response (P=0.035) were significantly related to PFS. In the PD-1 inhibitors plus IMRT group, 1 patient (2.2%) achieved complete response (CR), 30 (65.2%) had partial remission, and 14 (30.4%) had stable disease. There was no case with CR by IMRT or PD-1 inhibitors alone. Objective response rate (67.4%) and disease control rate (97.8%) were higher in the PD-1 inhibitors combined with IMRT group. In the PD-1 inhibitors plus IMRT and PD-1 inhibitors alone groups, hepatitis B virus (HBV)-positive patients had better OS (P=0.041) on UVA. Meanwhile, in the PD-1 inhibitors plus IMRT group, we observed superior PFS (P=0.041) and OS (P=0.049) in HBV-positive patients on UVA. Conclusions: PD-1 inhibitors plus IMRT may be a better method for advanced GI cancer patients with RPLN metastases. HBV-positive patients can benefit from either PD-1 inhibitors alone or in combination with IMRT.
