Prognostic Biomarker For Gastric Cancer Patients Research Articles

Correlation between the C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index and the prognosis of gastric cancer patients after gastrectomy: a systematic review and meta-analysis.

The C-Reactive Protein (CRP)-Albumin-Lymphocyte (CALLY) index is an established immuno-nutritional scoring system. We screened relevant literature from the major databases up until May, 2024, and extracted the data for analysis. A total of 2829 gastric cancer (GC) patients from six studies were included in this meta-analysis, the results of which revealed that the CALLY index was an independent prognostic factor for OS and RFS in both univariate analyses and multivariate analyses, and that a high CALLY index was a favorable prognostic factor. Moreover, GC patients in the high CALLY index group seemed to have better 5-year OS and 5-year RFS than those in the low CALLY index group. There was a higher proportion of patients with T1 status in the high CALLY index group than in the low CALLY index group. However, the opposite results were found in the analyses of lymph node metastasis positivity, lymph-vascular invasion positivity, postoperative complications, differentiated histological type, anastomotic leakage, and adjuvant chemotherapy. The present meta-analysis concluded that the CALLY index was a simple and useful independent prognostic biomarker for GC patients after gastrectomy.

Association of miR-338-3p with survival outcomes in gastric cancer patients who received peri-operative blood transfusion.

Perioperative blood transfusion (BT) is frequent in the treatment of gastric cancer (GC), but its effects on the prognosis of GC remains controversial. In this study, we aimed to further confirm the relationship of perioperative BT with GC overall survival and to evaluate the predictive value of microRNA-338-3p (miR-338-3p) for the prognosis of GC patients who received perioperative BT. Clinical data and serum samples were collected and analyzed from 246 patients with GC. Five-year follow-up survival information was assessed by Kaplan-Meier survival analysis. miR-338-3p relative expression was assessed by RT-qPCR, and its relationship with the prognosis of GC patients, who received perioperative BT, was evaluated using Kaplan-Meier curves and Cox regression analysis. GC patients received perioperative BT had poor 5year survival than those without BT. In patients received BT, miR-338-3p expression was higher in survival cases than died population and high miR-338-3p was independently associated with better overall survival prognosis. Perioperative BT is related with poor prognosis in GC patients and miR-338-3p may be a prognostic biomarker for GC patients received perioperative BT. BT in perioperative GC patients should be cautious, especially for those with low levels of miR-338-3p.

Expression and Clinical Significance of PIEZO2 in Gastric Cancer.

The aim of this research was to investigate the expression of PIEZO2 and its potential clinical significance in gastric cancer (GC). In this study, we detected the protein expression levels of PIEZO2 in GC tissues and adjacent normal tissues by immunohistochemistry (IHC) and analysed the relationship between the protein expression levels of PIEZO2 and clinicopathological parameters of GC patients. Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan-Meier Plotter were used to verify the diagnostic and prognostic values of PIEZO2. Proteins interacting with PIEZO2 were predicted using the SRING database. Our results showed that the protein expression levels of PIEZO2 in GC tissues were lower than those in adjacent normal tissues (all P < 0.05), and the protein expression level of PIEZO2 was correlated with lymph node metastasis and TNM stage of GC patients (all P < 0.05). Aberrant overexpression of PIEZO2 was associated with poor prognosis of GC patients. Proteins such as VR1, TRPV1, LHFPL5, STOM, TRPA1 and STOML3 had obvious interactions with PIEZO2 (P = 0.00213). In summary, our current study identified PIEZO2 as a promising target for early diagnosis and as a potential prognostic biomarker in GC patients.

Identification of RNF150 as the hub gene associated with microsatellite instability in gastric cancer

Gastric cancer (GC) is a common digestive tract malignancy with the sixth global incidence and third cancer-related deaths, respectively. Microsatellite instability (MSI), accounting for one of the molecular subtypes of GC, plays an important role in GC and is affected by a sophisticated network of gene interactions. In this study, we aimed to explore the expression pattern and clinical performance of MSI related gene in GC patients. Weighted gene co-expression network analysis (WGCNA) was exploited to single out the vital module and core genes in TCGA database. We applied the protein–protein interaction (PPI) and survival analysis to propose and confirm RNF150 as the hub gene in GC. Finally, we utilized immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) to explore the expression pattern of RNF150 in GC patients. With the highest weight correlation and standard correlation, RNF150 was selected as the hub gene for following validation. In validation, data obtained from the test sets showed a lower expression of RNF150 in MSI GC compared to microsatellite stability (MSS) GC. Moreover, survival analysis shows that MSI GC patients with a lower RNF150 expression level displayed the longer OS time. Compared to the expression in normal gastric tissues, the protein level of RNF150 was virtually up-regulated in ten cases of GC tissues. Furthermore, RNF150 protein level was decreased in MSI GC samples compared to MSS GC samples. When validated the mRNA expression with RT-PCR in fresh GC tissues, we also found the similar trend. RNF150 was identified as a novel MSI-related gene in GC. It is expected to be an auspicious prognostic biomarker for GC patients.

GHRL as a prognostic biomarker correlated with immune infiltrates and progression of precancerous lesions in gastric cancer.

Ghrelin is a protein that regulate appetite and energy balance in the human body, which is encoded by the ghrelin prepropeptide gene (GHRL). GHRL is linked with carcinogenesis and immune regulation. However, the correlation of GHRL to prognosis and tumor-infiltrating lymphocytes in gastric cancer (GC) remains unclear. In this study, we assessed the transcriptional expression, prognosis, and different clinicopathological features about GHRL and the correlation between GHRL and tumor infiltration immune cells in GC patients based on the data published in the following databases: TIMER, GEPIA, GEO, STRING, UALCAN, TISIDB, and Kaplan-Meier Plotter. Furthermore, R software analysis for GC Correa' cascade was also provided. Finally, GHRL expression in GC tissues was assayed using quantitative real-time polymerase chain reaction and immunohistochemistry. We found that GHRL expression in GC samples was lower than in normal samples and verified by quantitative PCR (qPCR) and immunohistochemistry. However, sample type, cancer stage, and worse survival were correlated to high GHRL expression. We also found that the expression of GHRL in dysplasia was significantly lower than that in CNAG and in GC. High GHRL expression was connected with immunomodulators, chemokines, and infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in GC. GHRL is a prognostic biomarker for GC patients, and it is correlated with progression of precancerous lesions in GC. It might lead to poor prognosis by regulating tumor immune microenvironment. Studies are important to explore therapeutic targeting GHRL in the future.

Postoperative circulating tumor DNA detection and CBLB mutations are prognostic biomarkers for gastric cancer

BackgroundSeveral studies have demonstrated that circulating tumor DNA (ctDNA) can be used to predict the postoperative recurrence of several cancers. However, there are few studies on the use of ctDNA as a prognosis tool for gastric cancer (GC) patients.ObjectiveThis study aims to determine whether ctDNA could be used as a prognostic biomarker in GC patients through multigene-panel sequencing.MethodsUsing next-generation sequencing (NGS) Multigene Panels, the mutational signatures associated with the prognosis of GC patients were identified. We calculated the survival probability with Kaplan–Meier and used the Log-rank test to compare survival curves between ctDNA-positive and ctDNA-negative groups. Potential application of radiology combined with tumor plasma biomarker analysis of ctDNA in GC patients was carried out.ResultsDisease progression is more likely in ctDNA-positive patients as characterized clinically by a generally higher T stage and a poorer therapeutic response (P < 0.05). ctDNA-positive patients also had worse overall-survival (OS: P = 0.203) and progression-free survival (PFS: P = 0.037). The combined analysis of ctDNA, radiological, and serum biomarkers in four patients indicated that ctDNA monitoring can be a good complement to radiological and plasma tumor markers for GC patients. Kaplan–Meier analysis using a cohort of GC patients in the TCGA database showed that patients with CBLB mutations had shorter OS and PFS than wild-type patients (OS: P = 0.0036; PFS: P = 0.0027).ConclusionsThis study confirmed the utility and feasibility of ctDNA in the prognosis monitoring of gastric cancer.

Overexpression of Copines-1 is associated with clinicopathological parameters and poor outcome in gastric cancer.

Copines-1 (CPNE1) is a soluble membrane-binding protein that includes two tandem C2 domains at the N-terminus and a C terminal A domain. Importantly, it is associated with the prognosis of various tumors, but there are only a few studies regarding the role of CPNE1 in gastric cancer (GC). This study aimed to explore the clinicopathological significance and prognostic potential of CPNE1 expression in GC. Data from the TIMER2.0 and UALCAN were analyzed to assess CPNE1 mRNA levels in GC. The prognostic role of CPNE1 mRNA was examined via the Kaplan-Meier plotter. CPNE1 protein expression in tumor tissues was analyzed via immunohistochemistry of clinical samples from 99 GC patients. The relationship of CPNE1 expression with clinicopathological parameters and overall survival (OS) was evaluated using Cox proportional hazards regression models and Kaplan-Meier survival curves. Copines-1 mRNA levels were higher in GC tissues than in adjacent normal tissue (ANT) (p< 0.05). Further, high CPNE1 mRNA expression indicated poor OS (p= 9.4 e-10) and was significantly associated with first progression (FP) (p= 1.6 e-06) and post-progression survival (PPS) (p= 1.5 e-12). In addition, CPNE1 protein expression was higher in GC tissues than in ANT (p< 0.0001). Moreover, CPNE1 high expression was significantly related to advanced tumor-node-metastasis (TNM) stage (p= 0.004), lymph node metastasis (p= 0.003), and vascular invasion (p= 0.001). Kaplan-Meier analysis showed that GC patients with high expression CPNE1 group had worse OS than low expression group (p= 0.003). Univariate analysis showed that age (hazard ratio [HR]=1.992; 95% confidence interval [CI], 1.009-3.934; p= 0.047), advanced TNM stage (HR=4.941; 95% CI, 2.052-11.897; p= 0.000), tumor invasion (HR=3.472; 95% CI, 1.349-8.937; p= 0.010), lymph node metastasis (HR=8.846; 95% CI, 2.708-28.897; p= 0.000), vascular invasion (HR=3.237; 95% CI, 1.521-6.891; p= 0.002), nervous invasion (HR=2.324; 95% CI, 1.205-4.479; p= 0.012), and CPNE1 expression (HR=3.464; 95% CI, 1.440-8.334; p= 0.006) were correlated with OS. In the multivariate analysis, age (HR=2.514; 95% CI, 1.264-4.999; p= 0.009), lymph node metastasis (HR=8.441; 95% CI, 2.553-27.906; p< 0.05), and CPNE1 expression (HR=2.549; 95% CI, 1.051-6.186; p= 0.039) were significant prognostic predictors for GC. Copines-1 overexpression in GC is significantly associated with poor prognosis. Thus, CPNE1 levels may serve as a prognostic biomarker in GC patients.

ITGAL as a Prognostic Biomarker Correlated With Immune Infiltrates in Gastric Cancer.

Integrin alpha L (ITGAL) is a member of the integrin family in which the abnormal expression is linked with carcinogenesis and immune regulation. However, the relation between ITGAL and the prognosis of gastric cancer (GC) and tumor-infiltrating lymphocytes (TILs) are not well understood. The differential expressions of ITGAL in human tumors and the clinical prognosis in GC were systematically analyzed via multiple databases including Gene Expression Profiling Interaction Analysis (GEPIA), UALCAN, Tumor Immune Estimation Resource (TIMER), and Kaplan–Meier (KM) plotter. TIMER, GEPIA, and TISIDB databases were used to comprehensively investigate the correlation between ITGAL and tumor infiltration immune cells. Also, further results were investigated by immunohistochemistry, qRT-PCR, and Western blot. We found that ITGAL expression in GC samples was considerably increased than in peritumor samples. Sample type, subgroup, cancer stage, lymphatic node stage, and worse survival were strongly related to high ITGAL expression. Moreover, upregulated ITGAL expression was strongly connected with immunomodulators, chemokines, and infiltrating levels of CD8+, CD4+ T cell, B cell, monocyte, neutrophil, macrophage, T-cell regulatory, NK cell, and myeloid dendritic cell in stomach adenocarcinoma (STAD). Specifically, immunohistochemistry and bioinformatic analysis showed that ITGAL expression was shown to have strong relationships with various immunological marker sets including PD1 (T-cell exhaustion marker). In conclusion, ITGAL is a prognostic biomarker for GC patients. It might regulate tumor immune microenvironment leading to poor prognosis. Furthermore, studies are essential to explore therapeutic targeting ITGAL.

High level of TXNDC9 predicts poor prognosis and contributes to the NF-κB-regulated metastatic potential in gastric cancer.

Gastric cancer (GC) is the most frequent malignant tumor in the digestive system, with high metastasis potential and poor prognosis. This study aimed to investigate the prognostic value and biological function of thioredoxin domain-containing protein 9 (TXNDC9) in GC. The expression of TXNDC9 was analyzed based on The Cancer Genome Atlas (TCGA) database. The prognostic value of TXNDC9 was evaluated by Kaplan-Meier curves and Cox regression analysis. The mRNA and protein expression of TXNDC9 were analyzed using quantitative real-time PCR and western blot analysis. The effects of TXNDC9 on GC cell invasion and EMT were assessed in vitro, and its effects on tumorigenesis were confirmed using animal experiments. The activity of the NF-κB signaling pathway was examined by both in vitro and in vivo experiments. TXNDC9 was highly expressed in GC tissues and cell lines. A high level of TXNDC9 was associated with poor overall survival and served as an independent prognostic biomarker in GC patients. The knockdown of TXNDC9 led to restrained GC cell invasion, microtubule formation, and EMT in vitro, and suppressed tumorigenesis in vivo. In addition, the NF-κB signaling pathway was demonstrated to mediate the functional role of TXNDC9 in GC. In conclusion, this study found that high TXNDC9 predicted poor prognosis in GC, and served as an oncogene by enhancing tumor cell invasion and EMT through the NF-κB signaling pathway.

Development of a two-circular RNA panel as potential prognostic biomarker for gastric cancer

BackgroundCircular RNAs (circRNAs) have attracted increasing attention in recent years for their potential application as disease biomarkers due to their high abundance and stability. In this study, we attempted to screen circRNAs that can be used to predict postoperative recurrence and survival in patients with gastric cancer (GC).MethodsHigh-throughput RNA sequencing was used to identify differentially expressed circRNAs in GC patients with different prognoses. The expression level of circRNAs in the training set (n = 136) and validation set (n = 167) was detected by quantitative real-time PCR (qRT-PCR). Kaplan–Meier estimator, receiver operating characteristic (ROC) curve and cox regression analysis were used to evaluate the prognostic value of circRNAs on recurrence-free survival (RFS) and overall survival (OS) in GC patients. CeRNA network prediction, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for the circRNAs with prognostic significance.ResultsA total of 259 differentially expressed circRNAs were identified in GC patients with different RFS. We found two circRNAs (hsa_circ_0005092 and hsa_circ_0002647) that highly expressed in GC patients with good prognoses, and subsequently established a predictive model for postoperative recurrence and prognosis evaluation, named circPanel. Patients with circPanellow might have shorter recurrence-free survival (RFS) and overall survival (OS). We also performed circRNA-miRNA-mRNA network prediction and functional analysis for hsa_circ_0005092 and hsa_circ_0002647.ConclusionsCircPanel has the potential to be a prognostic biomarker in GC patients with greater accuracy than a single circRNA and certain traditional tumor markers (e.g., CEA, CA19-9 and CA724).

The prognostic impacts of PABPC1 expression on gastric cancer patients.

Aim: To assess the prognostic impacts of PABPC1 on gastric cancer (GC) patients. Methods: The expression levels of PABPC1 in GC tissues and normal gastric tissues were initially compared via bioinformatics analysis. Immunohistochemicalstaining was accomplished to assess the expression of PABPC1 in the included GC patients. Then the impacts of PABPC1 expression on survival of GC patients were evaluated by Cox regression and Kaplan-Meier analyses. Results: The expression levels of PABPC1 in gastric tissues were significantly higher than those in normal gastric tissues (paired, p =0.002; unpaired, p =3.60e-9). By Kaplan-Meier, it was demonstrated that high expression of PABPC1 was significantly associated with worse overall and disease-free survival. Furthermore, high PABPC1 expression was demonstrated to be an independent predictive factor for both overall (p =0.013; hazard ratio =2.058; 95% CI: 1.162-3.644) and disease-free (p =0.018; hazard ratio =2.284; 95% CI: 1.153-4.524) survival. Conclusion: PABPC1 is a potential prognostic biomarker for GC patients.

Asporin represses gastric cancer apoptosis via activating LEF1-mediated gene transcription independent of β-catenin.

Asporin (ASPN) presents in the tumor microenvironment and exhibits a cancer-promoting effect as a stroma protein. Even though ASPN has already been observed inside cancer cells, the functions of intracellular ASPN and its underlying mechanisms remain unknown. Here we reported that ASPN was upregulated in different stages of gastric cancer (GC), and associated with a poor prognosis. Moreover, we found that ASPN markedly inhibited GC cell apoptosis and promoted cell growth in vitro and in vivo. Further mechanism investigations revealed that ASPN directly binding to lymphoid enhancer-binding factor 1 (LEF1) and promoted LEF1-mediated gene transcription independent of β-catenin, the classic co-factor in the Wnt/LEF1 pathway. We also demonstrated that ASPN selectively facilitated LEF1 binding to and activating the promoters of PTGS2, IL6, and WISP1 to promote their transcription. The suppression of cell apoptosis by ASPN overexpression could be attenuated by LEF1 knockdown or 100 µM aspirin (PTGS2 inhibitor), and siASPN mediated apoptosis could be rescued by LEF1 ectopic expression or adding recombinant IL6. Therefore, we concluded that ASPN repressed GC cell apoptosis via activating LEF1-mediated gene transcription independent of β-catenin, which could serve as a potential prognostic biomarker in GC patients.

Progesterone receptor gene serves as a prognostic biomarker associated with immune infiltration in gastric cancer: a bioinformatics analysis.

BackgroundGastric cancer (GC) is one of the most prevalent cancers globally with a poor prognosis. The progesterone receptor gene (PGR), which encodes the progesterone receptor (PR), can modulate the immune response in many cancers, but its correlation with prognosis and immune infiltration in GC remains unclear. We aimed to investigate the relationship between PGR expression and prognosis in GC patients.MethodsThe expression profile was obtained and the relationship between PGR expression and cancer prognosis was analyzed by Oncomine, Tumor Immune Estimation Resource (TIMER), Kaplan-Meier plotter, the PrognoScan database and Gene Expression Profiling Interactive Analysis (GEPIA) database using the minimum P value approach and log-rank method for prognosis analysis. Next, the correlation between the expression level of PGR and immune cell infiltration by the Spearman method using TIMER and GEPIA.ResultsA correlation of elevated PGR expression with poorer prognosis in GC was observed, with overall survival (OS) hazard ratio (HR) was 1.74 [95% confidence interval (CI): 1.4–2.17, P value =6.2e-7] and progression-free survival (PFS) HR was 2.09 (95% CI: 1.58–2.78, P value =1.6e-7). Also, high expression of PGR was related to worse OS and PFS in patients of each N stage in GC, with the highest OS and PFS HR values in stage N1. PGR expression in stomach adenocarcinoma (STAD) was significantly correlated with levels of B cells, CD8+T cells, CD4+T cells, macrophages, neutrophils and dendritic cells. It was also observed that PGR expression was related to a variety of immune cell markers.ConclusionsPGR expression correlated with prognosis and immune cell infiltration in GC, indicating PGR is a potential prognostic biomarker in GC patients.

LINC00665 promotes cell proliferation, invasion, and metastasis by activating the TGF-β pathway in gastric cancer

Background and AimsAccumulating studies have demonstrated that long noncoding RNA plays a vital role in cancer progression. A previous study reported that LINC00665 was overexpressed and acted as a key tumor promoter in lung cancer, but the role of LINC00665 in gastric cancer (GC) remained uncharacterized. Thus, this study aimed to explore the mechanism of LINC00665 in GC. MethodsLINC00665 expression was explored using the Cancer Genome Atlas (TCGA), and a meta-analysis was conducted to assess the expression and prognostic value of LINC00665 in GC from Gene Expression Omnibus databases and the TCGA dataset. Real-time polymerase chain reaction (RT-PCR) was then conducted to verify the LINC00665 expression in GC tissues and cell lines. The effects of LINC00665 on cell proliferation, invasion, metastasis, and cell cycle in GC were evaluated using the CCK-8, wound healing, Transwell, and flow cytometry assays. In vitro validation was also performed. ResultsLINC00665 overexpression was found in GC, and LINC00665 upregulation was significantly related to poor overall survival and disease-free survival. LINC00665 expression was associated with tumor depth, lymph node metastasis, and TNM stage. Univariate and multivariate analyses proved that LINC00665 could be an independent prognostic biomarker in GC. LINC00665 knockdown subsequently inhibited cell proliferation, invasion, and metastasis in GC cell lines; promoted cell apoptosis; and arrested GC cell lines in the G0/G1 phase. Western blot analysis indicated that LINC00665 silencing inhibited epithelial–mesenchymal transition and decreased the expression levels of TGF-β1, Smad2, and α-SMA. ConclusionLINC00665 can be a potential diagnostic and prognostic biomarker for GC patients, and LINC00665 promotes GC cell proliferation, invasion, and metastasis by activating the TGF-β signal pathway.

Trim47 overexpression correlates with poor prognosis in gastric cancer.

Trim47 is a member of the tripartite motif (TRIM) family that participates in many pathophysiological processes. However, the expression pattern and biological functions of Trim47 in gastric cancer (GC) remain unclear. The present study aimed to further explore the clinicopathological significance and potential prognostic role of Trim47 expression in GC. Therefore, in this study, Trim47 mRNA level was investigated in the Cancer Genome Atlas (TCGA) and Oncomine database in GC. We detected Trim47 mRNA and protein expression levels in GC and paired adjacent normal tissues. Kaplan-Meier method and Cox proportional hazard regression models were performed to analyze the survival of patients and prognostic factors. A gene set enrichment analysis (GSEA) was performed to determine the mechanism of Trim47 in GC. Our results indicated that Trim47 mRNA expression in GC tissues was significantly higher than adjacent normal tissues, as was Trim47 protein expression. Trim47 overexpression in GC tissues was significantly associated with tumor differentiation, T stage, N stage, M stage, and TNM stage. Kaplan-Meier analyses showed that high Trim47 expression was associated with worse overall survival (OS) and disease-free survival (DFS) in GC patients. Multivariate analysis confirmed that Trim47 expression was an independent prognostic factor for GC patients. Bioinformatics analysis and western blot indicated Trim47 might regulate GC through NF-κB, EMT, hypoxia, and apoptosis signaling pathway in GC. Our results show that Trim47 has the potential to serve as a novel prognostic biomarker in GC patients.

An Iron Metabolism-Related SLC22A17 for the Prognostic Value of Gastric Cancer.

PurposeGastric cancer (GC) is a type of malignant cancer with a poor prognosis. The iron’s metabolism plays an important role in the process of GC. The aim of this study was to evaluate the effectiveness of SLC22A17, associated with iron metabolism, in predicting the prognosis of GC patients.Materials and MethodsWe analyzed genes related to iron metabolism of gastric cancer mRNA-seq data from TCGA database. We identified an iron metabolism-related SLC22A17 as an independent prognostic factor using univariate and multivariate Cox regression analysis.ResultsFurther research showed that SLC22A17 was related with many pathways involved in the process of gastric cancer, and the expression was associated with diverse cancer-infiltrating immune cells. The expression of SLC22A17 was associated with T (Topography).ConclusionWe validated that SLC22A17 associated with iron metabolism could serve as a prognostic biomarker for GC patients.

USP19 Enhances MMP2/MMP9-Mediated Tumorigenesis in Gastric Cancer.

BackgroundTo investigate the clinical significance of ubiquitin-specific peptidase 19 (USP19) expression in gastric cancer (GC) compared with that in normal tissues and gastric cell lines.MethodsUSP19 protein expression was analyzed in 212 paired GC samples using immunohistochemical staining. Quantitative real-time PCR (qRT-PCR) and Western blotting were used to detect the level of USP19 in gastric cell lines. The biological functions of USP19 were investigated by MTT assay, colony-forming assay, wound healing assay and gelatin zymography, and apoptotic cells were detected by immunohistochemistry assays in SGC7901 xenograft models.ResultsUSP19 expression was significantly increased in GC cells and tissues, and the high level of USP19 expression was positively correlated with the Lauren’s classification and poor prognosis. Moreover, USP19 was identified as a novel independent prognostic biomarker in GC patients. Enhanced USP19 expression promoted GC cell proliferation and metastasis through reduced cleaved caspase-3 and increased MMP2/MMP9 expression and promoted enzyme activity in the study, and verified the results through The Cancer Genome Atlas (TCGA) and bioinformatic websites from the Kaplan–Meier plotter (http://kmplot.com) and GEPIA (http://gepia2.cancer-pku.cn.).ConclusionOur study suggests that USP19 promoted tumor progression by inducing MMP2/MMP9 expression and related enzyme activity. Hence, USP19 may be a valuable prognostic predictor for GC, and the USP19-MMP2/MMP9 axis could serve as a therapeutic target.

Increased long non-coding RNA ARAP1-AS1 expression and its prognostic significance in human gastric cancer: a preliminary study.

Multiple studies have unveiled that long non-coding RNAs (lncRNAs) contribute to oncogenesis. LncRNA ARAP1 antisense RNA 1 (ARAP1-AS1) has been demonstrated to serve as an oncogene in bladder tumor and colorectal cancer. This study attempted to explore the correlation of ARAP1-AS1 expressions with clinical progress and prognosis in gastric cancer (GC) patients. RT-PCR was carried out to examine the levels of ARAP1-AS1 in 157 GC patients. The associations between ARAP1-AS1 expression and clinicopathologic features in GC patients were analyzed using the Chi-square test. The prognostic value of abnormally expressed ARAP1-AS1 in GC patients was further analyzed via Kaplan-Meier assays and multivariate survival assays. The levels of ARAP1-AS1 were dramatically increased in GC samples compared with paired adjacent non-tumor specimens (p=0.01). The upregulation of ARAP1-AS1 was distinctly associated with TNM stage (p=0.010) and lymphatic metastasis (p=0.007). Further survival study revealed that patients with higher levels of ARAP1-AS1 had shorter overall survival (p=0.0020) and disease-free survival than those with lower levels of ARAP1-AS1. Finally, multivariate survival assay identified ARAP1-AS1 upregulation as an independent unfavorable prognostic factor in GC patients. Our preliminary results identified a novel GC-related factor, ARAP1-AS1 which may be a potential prognostic biomarker for GC patients.

LCP1 is a prognostic biomarker correlated with immune infiltrates in gastric cancer

Previous studies have identified LCP1 as a diagnostic and prognostic marker in several cancers. However, the role of LCP1 in gastric cancer (GC) and its effect on tumor immune infiltration remain unclear. The aim was to explore the role of LCP1 in GC and its effect on tumor immune infiltration. We explored the expression of LCP1 relative to clinicopathology in GC patients by bioinformatics analysis and immunohistochemistry. Using cBioportal database, we analyzed the characteristic genetic variations of LCP1 in GC. In addition, we evaluated the correlation between LCP1 expression and tumor-infiltrating lymphocytes (TILs) using R software, TIMER and TISIDB databases. Finally, we analyzed the biological functions in which LCP1 may participate and the signaling pathways it may regulate. Here, we showed that LCP1 expression is significantly correlated with tumor aggressiveness and poor prognosis in GC patients. Additionally, the results indicated that LCP1 was associated with TILs, including both immunosuppressive and immunosupportive cells, and was strongly correlated with various immune marker sets in GC. GSEA analysis demonstrated that LCP1 expression played an important role in lymphocyte formation and immune reaction. LCP1 may be a potential prognostic biomarker for GC patients and a marker for tumor immunotherapy.

Knockdown of LINC02465 Suppresses Gastric Cancer Cell Growth and Metastasis Via PI3K/AKT Pathway.

Gastric cancer (GC) is the second primary cause of cancer-associated mortality around the world. Long noncoding RNAs (lncRNAs) are critical modulators of multiple cellular processes, and their abnormal expression and/or function are related to a variety of diseases, including cancer. Various lncRNAs have been shown to exert a functional role in GC, but more still remain to be identified, since the therapies for GC patients are limited. Here we discover LINC02465, a novel recognized lncRNA, is upregulated and correlated with tumor size, tumor stage, lymph node metastasis, and differentiation in gastric cancer. In addition, we found that high LINC02465 level in GC patients is closely related to poor prognosis. Moreover, our findings reveal that LINC02465 silence suppresses cell proliferation and migration, invasion, and epithelial-mesenchymal transition in vitro. Conversely, LINC02465 overexpression displays a completely opposite way. Meanwhile, LINC02465 inhibition also limits tumor growth in vivo. Mechanistically, LINC02465 inhibition inactivates PI3K/AKT signaling pathway, and the activation of this pathway by 740Y-P reverses the inhibition effect of LINC02465 suppression on biological behaviors of GC cells. Taken together, LINC02465 is an oncogenic lncRNA that facilitates the tumorigenesis and progression of GC via PI3K/AKT pathway, demonstrating a novel effective therapeutic target and prognostic biomarker for GC patients.