1.Clinical value of bone morphogenetic protein antagonist GREM1 as an immuno-active indicator in tumor microenvironment of gastric cancer
Xudong ZHANG ; Xiaoning LI ; Haikang CUI ; Xi YANG ; Lan YANG ; Wenjie ZHANG
Chinese Journal of Immunology 2024;40(4):741-751
Objective:To screen prognostic genes as indicators for predicting immunoactive in tumor microenvironment(TME)of gastric cancer(GC).Methods:Paraffin tissue specimens and corresponding paracancer tissues were collected from 55 patients with GC.Total 976 GC transcriptome RNA-Seqs and clinical datasets were obtained from TCGA and GEO databases.Infiltra-tion status of immune cells and Immune/Stormal scores were calculated using the ESTIMATE and CIBERSORT algorithm.R package"limma"was performed to selected differentially expressed genes(DEGs).Univariate Cox regression analysis was used to determine prognostic factors of DEGs.qRT-PCR was demonstrated to detect mRNA expression of the hub genes.Potential biological functions of GREM1 were investigated by GSEA.Correlations of GREM1 with immune signature molecules and drug susceptibility were investigated by TISIDB and CellMiner database.Results:Immune Score was positively correlated with improved outcomes of GC patients.A total of 40 shared TME-related DEGs were selected in the high and low groups of Immune Score and Stromal Score.Four survival-related DEGs were obtained by Cox analysis,which were GREM1,SFRP2,CYP1B1 and MGP.By comparing the difference of gene expres-sion in tumor and adjacent tissues and the degree of affinity with immune microenvironment,it was found that GREM1 was most likely to play a role in immune remodeling in TME;expression of GREM1 was positively correlated with clinicopathological features(TNM),while negatively correlated with survival time of GC patients.GSEA results showed that GREM1 high-expression group were mainly enriched in immune-related active genomes.Besides,GREM1 expression was positively correlated to M2 macrophages,while negatively correlated to CD8+T cells.GREM1 was also positively associated with immunosuppressor TGF-β1,immunopotentiator ENT-PD1,chemokine CCL14 as well as receptor CCR2.Moreover,GC patients with high expression of GREM1 might more sensitive to drug Vismodegib therapy.Conclusion:GREM1 can regard as an immunosuppressive clinical indicator in TME of GC.
2.Pathological significance of p-STAT3 and Survivin expression in gastric cancer and establishment of preoperative prognostic model
Wen Yue ; Xiaojun Wang ; Miaomiao Ma ; Dandan Zhang ; Feng Pan ; Jiaqi Nie ; Xiaoning Li ; Haikang Cui ; Lan Yang ; Wenjie Zhang
Acta Universitatis Medicinalis Anhui 2022;57(5):816-822
Objective:
To investigate the relationship between the expression of p-Stat3 and Survivin in gastric cancer and the clinical characteristics and prognosis of patients, and to establish the prediction model of postoperative survival of patients combined with alanine aminotransferase(ALT) and aspartate aminotransferase(AST).
Methods:
Data of 133 patients undergoing gastric tumor resection were collected and followed up. The expression of p-STAT3 and Survivin in gastric cancer and precancerous tissues were detected by immunohistochemical method. Kaplan-Meier method was used to draw the survival curve. Logistic regression model combined with receiver operating characteristic curve(ROC) curve was used to describe the predictive value of multi-index combined detection on postoperative survival status of patients. The prediction model of the histogram was established using Survival and RMS packages in R Studio software.
Results:
The expressions of p-Stat3 and Survivin in gastric cancer tissues were higher than those in precancerous tissues. The expression of p-Stat3 in gastric cancer tissues was positively correlated with the depth of invasion and TNM stage, while the expression of Survivin in gastric cancer tissues was positively correlated with the degree of differentiation and the depth of invasion. The higher the expression levels of p-Stat3 and Survivin, the worse the prognosis. The lower the ALT level, the worse the prognosis. Survivin, ALT and AST were the optimal combination for predicting postoperative survival in patients with gastric cancer.
Conclusion
The expression of p-Stat3 and Survivin plays an auxiliary role in the diagnosis of gastric cancer. P-Stat3, Survivin and ALT are correlated with the prognosis of patients with gastric cancer and have predictive value. Survivin, ALT and AST combined model has a big value to predict the postoperative survival prognosis of gastric cancer patients, which can provide a reference for clinical practice.