The Prognostic Significance and Gene Expression Characteristics of Gastric Signet-Ring Cell Carcinoma: A Study Based on the SEER and TCGA Databases

Abstract

PurposeThis study is based on the Surveillance, Epidemiology, and End Results (SEER) program to explore the prognostic differences between signet-ring cell carcinoma (SRC) and intestinal-type gastric carcinoma (ITGC). This study is also based on gene sequencing data from The Cancer Genome Atlas (TCGA) to identify unique genetic contributions to the prognostic differences between the two subtypes of gastric cancer.Patients and MethodsThe clinical data were based on the SEER database from 2004 to 2015. Kaplan–Meier (KM) curves were used to compare 5-year overall survival (OS), and Cox regression was used for univariate and multivariate analyses. Gene expression profiles were obtained from TCGA database, and differentially expressed genes (DEGs) were screened. Functional enrichment analysis, protein interaction and survival analysis will be further carried out. Genes of interest were verified by the Human Protein Atlas, immunohistochemistry, and encyclopedia of Cancer Cell Lines (CCLE). The relationship between genes of interest and immune cell infiltration was also analyzed by Tumor Immune Estimation Resource (TIMER).ResultsCompared with ITGC patients, SRC patients were more likely to be female, tended to be younger, and have a greater tumor distribution in the middle and lower stomach (p < 0.01). SRCs showed a significantly better prognosis than ITGCs (p < 0.01) in early gastric cancer (EGC), while the prognosis of SRCs was significantly worse than ITGCs (p < 0.05) in advanced gastric cancer (AGC). A total of 256 DEGs were screened in SRCs compared to ITGCs, and the enrichment analysis and protein interactions revealed that differential genes were mainly related to extracellular matrix organization. Thrombospondin1 (THBS1) and serpin peptidase inhibitor, clade E, member 1 (SERPINE1) are significantly differentially expressed between SRC and ITGC, which has been preliminarily verified by immunohistochemistry and open-source databases. THBS1 and SERPINE1 are also associated with multiple immune cell infiltrates in gastric cancer.ConclusionsThere were significant differences in the clinicopathological features and prognosis between SRC and ITGC. These results suggest that SRC and ITGC may be two distinct types of tumors with different pathogeneses. We found many codifferentially expressed genes and important pathways between SRC and ITGC. THBS1 and SERPINE1 were significantly differentially expressed in the two types of gastric cancer, and may have potentially important functions.

Evaluation of CEP55, SERPINE1 and SMPD3 genes and proteins as diagnostic and prognostic biomarkers in gastric carcinoma in Egyptian patients

“…Ma et al [34] correlated with the present results as they revealed that SERPINE1 was associated with poor prognosis of GC by being involved in multiple immune cell infiltrates in gastric cancer. Also, Akhavan et al [35] agreed with the present findings as they identified SERPINE1 as one of the four genes upregulated in GC suggesting that these genes being predicted targets of hsa-miR-421 and hsa-miR-193a-3p.…”

Transcriptome sequencing reveals candidate genes and signaling pathways for skeletal muscle development in Ningxiang pig

“…The molecular interactions in the process of gene expression include transcription factor-transcription initiation factor, transcription factor-cofactor, cofactor-cofactor, translation initiation factor-cofactor, modi cation factor and so on. The interaction between serpine 1 and THBS1 has been veri ed in the process of gastric cancer and luteinization in endothelial cells [50,51]…”

Early onset, development and histological features of gastric signet-ring cell carcinoma

“…This stage of carcinoma is the classical early gastric SRCC. It includes classical-type signet-ring cell (the cell is round, with a diameter of 15-30 mm and reddish mucous substances in the cytoplasm; the nucleus is deviated, and is signet-ring or crescentshaped), and those that we previously reported: juvenile signet-ring cell (the cell is round or irregular, and the cytoplasm is strongly eosinophilic; the nucleus is irregularly round or oval, and deviated, and the ratio of nucleus to cytoplasm is 1:1-3; the nuclear chromatin is basophilic and eosinophilic); hyperproliferative type signet-ring cell (the cell is round or oval, the cytoplasm is uniform and slightly stained with basophilic and eosinophilic mucus; the nucleus is large with a prominent nucleolus, and is deviated); nuclear-free vacuolated signet-ring cell (the cell developed due to the relationship between sections during section preparation; the cell still maintained the cytoplastic outline and had reddish mucous substances in the cytoplasm); degenerative signet-ring cell (the size of the cell increased, and was mostly 20 mm-40 mm, or up to 50 mm; the membranes were incomplete, the nucleus was small and slightly stained, and gray, or it had no nucleus) (23). In this study, when small signet-ring cell carcinoma-like lesions or foveolar-type signet-ring cell carcinoma infiltrated into the lamina propria of the mucosa and the submucosa, signet-ring-like heterocysts and small signet-ring cell carcinoma-like lesions, after reproliferation, differentiated into various types of gastric adenocarcinoma with signet-ring cell…”

“…Multistage carcinogenesis of SRCC involving genetic and epigenetic aberrations is associated with stage-dependent prognosis (22). There are significant differences in clinicopathological features and prognosis between signet ring cell carcinoma (SRC) and intestinal type gastric cancer (ITGC) (23). In gastric cancer with signet ring cell (SRC) component, there is a good prognosis in stage I.…”

“…The results of our previous research revealed that H. pylori selectively adhered to and destroyed the cytoplasm of mucous cells on the surface of the gastric mucosa, causing the ovoid and spherical mucus-containing particles wrapped in limitans in the cytoplasm on the nucleus to disappear, the cytoplasm showed cobweb-like vacuolar degeneration, and the epithelial cells on the surface of the gastric mucosa exfoliated, leading to the proliferation and transformation of the mucous neck cells in the proliferative zone, the formation of papillary epithelioma-like hyperplasia of mucous cells on the surface of the gastric mucosa, the extensive and segmental atrophy of the lamina propria gland of the gastric mucosa, and other changes (21,22). Studies have shown H. pylori infection could cause foveolar-type signet-ring cell carcinoma, and the histopathological features and differential diagnosis of this type of gastric carcinoma have been proposed (23). A total of 362 patients with differentiated adenocarcinoma with signetring cells were enrolled in this study.…”