Dataset Information

Comprehensive Analysis to Identify MAGEA3 Expression Correlated With Immune Infiltrates and Lymph Node Metastasis in Gastric Cancer.

ABSTRACT: Gastric cancer (GC) is an aggressive malignant tumor and causes a significant number of deaths every year. With the coming of the age of cancer immunotherapy, search for a new target in gastric cancer may benefit more advanced patients. Melanoma-associated antigen-A3 (MAGEA3), one of the members of the cancer-testis antigen (CTA) family, was considered an important part of cancer immunotherapy. We evaluate the potential role of MAGEA3 in GC through the TCGA database. The result revealed that MAGEA3 is upregulated in GC and linked to poor OS and lymph node metastasis. MAGEA3 was also correlated with immune checkpoints, TMB, and affected the tumor immune microenvironment and the prognosis of GC through CIBERSORT, TIMER, and Kaplan-Meier plotter database analysis. In addition, GSEA-identified MAGEA3 is involved in the immune regulation of GC. Moreover, the protein-protein interaction (PPI) networks of MAGEA3 were constructed through STRING database and MAGEA3-correlated miRNAs were screened based on the joint analysis of multiple databases. In terms of experimental verification, we constructed pET21a (+)/MAGEA3 restructuring plasmids and transformed to Escherichia coli Rosetta. MAGEA3 protein was used as an antigen after being expressed and purified and can effectively detect the specific IgG in 93 GC patients' serum specimens with 44.08% sensitivity and 92.54% specificity. Through further analysis, the positive rate of MAGEA3 was related to the stage and transfer number of lymph nodes. These results indicated that MAGEA3 is a novel biomarker and correlated with lymph node metastasis and immune infiltrates in GC, which could be a new target for immunotherapy.

SUBMITTER: Jin J

PROVIDER: S-EPMC8712941 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ImportanceSegmental gastrectomy, a type of function-preserving surgery, is not broadly studied but can improve postoperative function and quality of life among patients with gastric cancer (GC).ObjectiveTo establish an indication for middle segmental gastrectomy (MSG) as a treatment for middle-body (MB) and high-body (HB) GC.Design, setting, and participantsThis cohort study analyzed patients with GC undergoing surgery between January 2000 and December 2015 in the National Cancer Center, Goyang, Korea, a high-volume cancer center with a structured database and accurate long-term follow-up. Inclusion criteria were age 18 to 85 year, histologically proven adenocarcinoma located in the HB or MB, cT1 to cT3 category cancers, curative resection with negative margins performed, and follow-up for at least 3 years. Exclusion criteria were Borrmann type 4 GC, T4 category cancer, neoadjuvant chemotherapy, and a history of other cancers. Data analysis was performed from December 2018 to May 2020.ExposuresTotal or subtotal gastrectomy and LN dissection.Main outcome and measuresThe primary outcome was the rate of metastasis at LN stations 2, 4sa, 5, 6, and 11d, which cannot be dissected during MSG.ResultsAmong 9952 patients who underwent surgery for GC, 8219 underwent either laparoscopic or open total or subtotal gastrectomy. Seven hundred seventy-three patients (mean [SD] age, 56.21 [12.16] years; 464 men [60.0%]) had GC in the MB or HB of the stomach. Among the 701 patients included in the final analysis after exclusion of the cN2/N3 carcinomas, the mean (SD) age was 56.35 (12.24) years, and 418 (59.6%) were men. The incidence of LN metastasis was 0% at station 5 for cT1-3N0/1M0 cancers, station 4sa for cT1-2N0/1M0 cancers, station 2 for cT1N0/1M0 cancers, station 6 for cT1N1M0 cancers, station 11d for cT1N1M0-cT2N0/1M0 cancers, and station 12a for cT1N0/1M0-T2N1M0 cancers, regardless of size and differentiation. The rates of LN metastasis for cT1N0M0 cancers were 0.3% (1 of 396 LNs) at station 6 and 0.8% (1 of 129 LNs) at station 11d. Tumors 4 cm or smaller were associated with a lower risk of LN metastasis compared with tumors 4.1 cm or larger (odds ratio, 2.10; 95% CI, 1.20-3.67; P = .009), and well-differentiated tumors were associated with lower risk of LN metastasis compared with poorly differentiated tumors (odds ratio, 2.88; 95% CI, 1.45-5.73; P = .002).Conclusions and relevanceThese findings suggest that MSG with dissection of stations 1, 3, 4sb, 4d, 7, 8a, 9, 11p, and 12a could be done for HB and MB cT1N0/1M0 gastric cancers 4 cm or smaller and well-differentiated cT2N0/1M0 cancers.

Project description:AimsRecent studies have shown that the microenvironment can include cancer cells and cancer-associated fibroblasts (CAFs), and that both play important roles in the progression and metastasis of CRC. Here, we aimed to analyse the expression patterns of cancer cell- and CAF-related proteins in submucosal invasive colorectal cancer (SiCRC) and whether such markers are correlated with lymph node metastasis (LNM).Methods and resultsQuantitative analysis was conducted for Ki-67, p53, β-catenin and matrix metalloproteinase-7 (MMP7) to assess cancer cell markers. In addition, we examined CAF markers, including smooth muscle alpha-actin (α-SMA), CD10, podoplanin, fibroblast-specific protein 1 (FSP-1), platelet-derived growth factor receptor (PDGFR)-α, PDGFR-β, adipocyte enhancer-binding protein 1 (AEBP1), fibroblast-associated protein 1 (FAP-1), zinc finger E-box binding homeobox 1 (ZEB1) and TWIST-related protein 1 (TWIST1). In both cases, we conducted digital pathology with Aperio software. We also examined the expression patterns of biomarkers using hierarchical cluster analysis. Two subgroups were established based on the expression patterns of cancer cell- and CAF- related markers, and the associations of these subgroups with clinicopathological variables. In multivariate analysis, subgroup 2, which was characterised by high expression of Ki-67, p53, FAP-1, platelet-derived growth factor receptor (PDGFR)-α, PDGFR-β and TWIST1, was correlated with LNM (P < 0.01). Next, we examined the associations of individual biomarkers with LNM. Multivariate analysis showed that high expression levels of Ki-67 and FAP-1 were significantly associated with LNM (P < 0.05).ConclusionsOur findings showed that expression patterns of cancer cell- and CAF-related proteins may allow for stratification of patients into risk categories for LNM in SiCRC. In addition, Ki-67- and FAP-1-expressing microenvironmental cells might be helpful for identification of correlations with LNM in SiCRC.

Dataset Information

Comprehensive Analysis to Identify MAGEA3 Expression Correlated With Immune Infiltrates and Lymph Node Metastasis in Gastric Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets