High expression of regulator of G‑protein signalling 1 is associated with the poor differentiation and prognosis of gastric cancer

Abstract

Emerging evidence has highlighted that immune and stromal cells form the majority of the tumour microenvironment (TME), which plays important roles in tumour progression. The present study aimed to screen vital prognostic genes associated with the TME in gastric cancer (GC). The ESTIMATE algorithm was applied to calculate TME-related scores, and the relationship between clinicopathological variables and these scores was analysed. Heatmaps and Venn plots were then used to visualize and screen differentially expressed genes. Furthermore, functional enrichment analysis was performed, and a protein-protein interaction network was constructed. Kaplan-Meier curves were generated to evaluate survival differences for each hub gene. Reverse transcription quantitative PCR was employed to evaluate the expression of the three hub genes in the validation cohort. The association between gene expression, clinicopathological variables and survival was also evaluated. Higher stromal scores were associated with worse outcomes in patients with GC. In addition, higher scores were significantly associated with a higher tumour grade, American Joint Committee on Cancer stage and T stage with regard to immune scores, stromal scores and ESTIMATE scores, respectively. In total, 644 upregulated intersecting genes and 126 downregulated genes were identified. Moreover, 71 TME-associated hub genes were identified. Batch survival analysis revealed that higher expression of CXCR4, PTGFR and RGS1 was significantly associated with worse outcome. Subsequently, the relationship between high expression of RGS1 and poor prognosis was verified, and high expression of RGS1 was associated with poor differentiation. In conclusion, it was found that compared with immune cells, stromal cells may play a more important role in the prognosis of patients with GC. In addition, the influence of RGS1 expression on survival in GC patients was identified and verified, and high expression of RGS1 was found to be associated with a low differentiation degree of GC.

Identification and Validation of a Malignant Cell Subset Marker-Based Polygenic Risk Score in Stomach Adenocarcinoma Through Integrated Analysis of Bulk and Single-Cell RNA Sequencing Data

“…RAMP1 has been found to be a cancer-promoting gene in many studies ( Logan et al, 2013 ; Mishima et al, 2017 ; Dallmayer et al, 2019 ). RGS1 is the marker gene of malignant cell cluster 8 and has been associated with poor prognosis in the present work and in a previous study ( Li et al, 2021 ). However, another study failed to detect such an association ( Zhu et al, 2021 ).…”

Single cell transcriptome analysis reveals RGS1 as a new marker and promoting factor for T cell exhaustion in multiple cancers

“…RGS1 inhibits the chemokine-induced lymphocyte migration(50) because chemokine-dependent activation of G-protein-coupled receptors can cause the activation of heterotrimeric G-protein subunits resulting in enhanced cell migration and adhesion(51), which has been found in Treg cells(45). In the present study, RGS1 was highly expressed in tumor tissues and correlated with shorter overall survival, which also appeared in several previous studies, including multiple myeloma(52), melanoma(53, 54), non-small cell lung cancer(55), gastric cancer(56), diffuse large B cell lymphoma(57) and so on. However, the role of RGS1 in CD8+T cells especially in Tex cells has not been reported.…”

MicroRNA-376b-3p targets RGS1 mRNA to inhibit proliferation, metastasis, and apoptosis in osteosarcoma

“…During vitiligo development, RGS1 overexpression is related to cluster of differentiation (CD)4 + T cell abundance (18). High expression of RGS1 is closely related to the progression and prognosis of several tumors, including gastric cancer (19) and hepatocellular carcinoma (13). Chromosomal rearrangement occurs in the development of lymphoid cells (20).…”