Expression of carbohydrate antigen sialyl Le(a): a new functional prognostic factor in gastric cancer.

PURPOSE The prognostic value of the altered expression of carbohydrate antigens sialyl Le(a) (sLe(a)) and sialyl Le(x) (sLe(x)), which have been implicated as functional ligands in heterotypic-cell-adhesion systems in the multistep process of tumor metastasis, were evaluated. PATIENTS AND METHODS The level of expression of sLe(a) and sLe(x) antigens was examined immunohistochemically in paraffin-embedded tumor samples from 137 patients who underwent resection for gastric cancer. Correlation between the antigens' expression, various established clinicopathologic factors, and prognosis were studied by univariate and multivariate analysis. RESULTS Tumors that were positive for the sLe(a) antigen were significantly more likely to be large (P = .035), to be localized at the proximal third of the stomach (P = .018), to have an infiltrate appearance (P = .013), to have an invasive mode both in depth of invasion (P = .028) and in lymphatic invasion (P = .002), and to be classified as late stage (P = .011) than those that were negative for sLe(a), whereas the sLe(x) antigen status was not correlated with any clinicopathologic factors. The overall survival of patients with an sLe(a)-antigen-positive tumor was significantly poorer than that of those with an sLe(a)-antigen-negative tumor (P = .0001). Survival within each pathologic stage differed also (stage I, P = .030; stage II, P = .046; stage III, P = .026, respectively). A Cox regression analysis with multiple covariates showed that positive sLe(a) antigen status was an independent prognostic factor for a worse outcome in patients with gastric cancer. According to the mode of recurrence, increased sLe(a) antigen expression significantly affected both peritoneal dissemination and liver metastasis. CONCLUSION Increased expression of the sLe(a) antigen may serve as a potent prognostic indicator for recurrence in patients with gastric cancer. Careful follow-up and intensive therapy are required for patients with an sLe(a)-antigen-positive gastric cancer.

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P2X7R as an independent prognostic indicator in gastric cancer

Bosnian Journal of Basic Medical Sciences ◽

10.17305/bjbms.2020.4620 ◽

2020 ◽

Cited By ~ 1

Author(s):

Ilknur Calik ◽

Muhammet Calik ◽

Burcu Sarikaya ◽

Ibrahim Hanifi Ozercan ◽

Ramazan Arslan ◽

...

Keyword(s):

Gastric Cancer ◽

Cox Regression ◽

Tumor Infiltrating Lymphocytes ◽

Prognostic Indicator ◽

P2x Receptor ◽

Depth Of Invasion ◽

Human Gastric Cancer ◽

Free Oxygen Radicals ◽

Cox Regression Analysis ◽

Prognostic Parameter

Gastric cancer is one of the foremost causes of cancer related death around the world. The P2X7 receptor (P2X7R), a member of the P2X receptor subfamily of P2 receptors, is a unique molecule that has been shown to affect tumor growth and progression as well as various inflammatory processes, including proliferation of T lymphocytes, release of cytokines, and production of free oxygen radicals. P2X7R has been established as a prognostic parameter in some cancers and, recently, it has been investigated in the development of new targeted therapies. In the present study, we aimed to investigate the prognostic value of P2X7R expression in GC. The expression profile of P2X7R was evaluated immunohistochemically in 156 paraffin-embedded human gastric cancer specimens. P2X7R expression was higher in patients with lymph node metastasis than in those without (p < 0.001). P2X7R overexpression was closely related with tumor-infiltrating lymphocytes [TILs] (p = 0.001), vascular invasion (p = 0.006), depth of invasion (p < 0.001), distant metastasis (p < 0.001), and advanced TNM stage (p < 0.001). Moreover, univariate (HR 3.98; 95% CI 1.89–11.82; p < 0.001) and multivariate (HR 2.24; 95% CI 3.53–12.50; p < 0.001) Cox regression analysis showed that upregulated P2X7R expression clearly correlated with worsened overall survival. In summary, our data revealed that P2X7R may serve as a reliable prognostic parameter and promising therapeutic target for gastric cancer.

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Predictive value of the serum RASSF10 promoter methylation status in gastric cancer

Journal of International Medical Research ◽

10.1177/0300060519848924 ◽

2019 ◽

Vol 47 (7) ◽

pp. 2890-2900 ◽

Cited By ~ 1

Author(s):

Yilin Hu ◽

Peng Ma ◽

Ying Feng ◽

Peng Li ◽

Hua Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Promoter Methylation ◽

Cox Regression ◽

Methylation Status ◽

Disease Free Survival ◽

Prognostic Indicator ◽

Chronic Atrophic Gastritis ◽

Survival Times ◽

Cox Regression Analysis ◽

Specific Pcr

Background This study aimed to investigate whether the detection of methylation in the promoter of the Ras association domain family 10 gene ( RASSF10) in the serum of patients with gastric cancer (GC) by methylation-specific PCR (MSP) can be used as a diagnostic and prognostic indicator of GC. Methods We used MSP to examine RASSF10 methylation levels in the serum and/or tumor samples from 100 GC patients, 50 patients with chronic atrophic gastritis (CAG), and 45 healthy controls (HC). We also analyzed clinicopathological and follow-up data. Results Our results showed that the rate of serum RASFF10 promoter methylation among patients with GC (49/100) was higher than in those with CAG (1/50) or HC (0/45). Moreover, the RASSF10 methylation status was consistent between serum and tumor tissues. GC patients with serum RASSF10 promoter methylation had significantly shorter overall survival and disease-free survival times than GC patients without serum RASSF10 promoter methylation. Multivariable Cox regression analysis showed that serum RASSF10 promoter methylation and lymph node metastasis both correlated with reduced survival in GC patients. Conclusions Detection of the serum RASSF10 methylation status by MSP is feasible as a diagnostic and prognostic indicator of GC.

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The prognostic impact of hypoxia-inducible factor-1α and VEGF, IGF-2, p21, p53 expression in gastric adenocarcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.4571 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 4571-4571

Author(s):

Y. Kakeji ◽

K. Mizokami ◽

Y. Sumiyoshi ◽

K. Yoshinaga ◽

H. Saeki ◽

...

Keyword(s):

Gastric Cancer ◽

Growth Factor ◽

Cox Regression ◽

Hypoxia Inducible Factor ◽

Depth Of Invasion ◽

Human Gastric Cancer ◽

Prognostic Impact ◽

P53 Expression ◽

Cox Regression Analysis ◽

Dismal Prognosis

4571 Background: Hypoxia caused by either radiation or chemotherapy induces various intracellular adaptive responses, which contribute to tumor progression. The clinicopathological characteristics of human gastric cancer and the clinical outcomes were analyzed to investigate the effects of the expression of hypoxia-inducible factor1α (HIF-1α) and some related proteins, such as, vascular endothelial growth factor (VEGF), insulin-like growth factor-2 (IGF-2), p21, and p53 on the prognosis of human gastric cancer. Methods: The expressions of HIF-1α, VEGF, IGF-2, p21, and p53 proteins were determined by immunohistochemistry in 216 specimens of primary gastric cancer. Results: Of all 216 patients, 85 (39.4%) showed a positive expression of HIF-1α. In addition, the HIF-1α expression positively correlated with the tumor size and depth of invasion, while it was also more frequent in tumors with lymphatic invasion and undifferentiated adenocarcinomas. Though the VEGF expression significantly correlated with the HIF-1α expression, the expressions of IGF-2, p21 and p53 did not show any correlation. HIF-1α-positive/p21-negative tumors had a lower apoptotic index, and the patients with such tumors also had a significantly poorer prognosis. Similarly, HIF-1α-positive/p53-positive tumors had a significantly poorer prognosis. A multivariate Cox regression analysis showed the depth of invasion, lymph node metastasis, and HIF-1α positivity to all be independent prognostic factors in patients with gastric cancer. Conclusions: Based on the above findings, HIF-1α is therefore considered to be a useful independent prognostic factor in gastric cancer, and the combination of a HIF-1α protein overexpression with the loss of p21 expression or nonfunctional p53 thus tends to indicate a dismal prognosis. Controlling hypoxia, especially in the HIF-1α pathways, may therefore hold the key to a greater individualization of therapy and also lead to the development of new treatments for patients with gastric cancer. No significant financial relationships to disclose.

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High Expression of PABPC1 Predicts Worse Survival of Gastric Cancer Patients

10.21203/rs.3.rs-99696/v1 ◽

2020 ◽

Author(s):

Tailai An ◽

Lingna Deng ◽

Zheng Yang ◽

Cuicui Chai ◽

Yan Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Regression Analysis ◽

Molecular Mechanisms ◽

Bioinformatics Analysis ◽

Cox Regression ◽

Disease Free Survival ◽

Mrna Translation ◽

High Expression ◽

Depth Of Invasion ◽

Cox Regression Analysis

Abstract Background: Gastric cancer (GC) is one of the most common cancers with one of the highest mortality rates. Unfortunately, underlying molecular mechanisms contributing to GC have not been fully illuminated. PABPC1 is involved in a series of processes, such as mRNA translation, and mRNA deadenylation and decay. We performed this study to clarify the role of PABPC1 in GC. Methods: To evaluate PABPC1 expressions in GC and normal tissues, we performed bioinformatics analysis of data from TCGA. PABPC1 expressions were evaluated by immunohistochemical (IHC) staining of 170 GC specimens. Associations between PABPC1 expression and clinicopathological variables were analyzed. Independent predictive factors for survival of GC patients were determined by Cox regression analysis. Results: It was revealed by bioinformatics analysis that compared with normal gastric tissues, PABPC1 expressions in GC tissues were significantly higher (P=0.002, paired) (P=3.605e^-9, unpaired). It was revealed that PABPC1 expression was significantly associated with tumor size (P=0.008), Borrmann classification (P=0.003), vessel invasion (P=0.017), depth of invasion (P=0.032), lymph node metastasis (P=0.001), and TNM stage (P=0.019). It was demonstrated through Cox regression analysis that PABPC1 expression was a predictive factor for both overall survival (OS) (P<0.001) and disease-free survival (DFS) (P<0.001) of GC patients. Conclusions: Compared with that of normal gastric tissue, expression level of PABPC1 in GC tissue was significantly higher and PABPC1,s high expression was significantly associated with poorer survival, suggesting its potential as a therapeutic biomarker for GC.

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Prognostic Significance of ACP5 in Human Gastric Cancer

Digestive Diseases ◽

10.1159/000513736 ◽

2020 ◽

Author(s):

Tailai An ◽

Qian Liang ◽

Tengfei Hao ◽

Lingna Deng ◽

Xiaofang Lu ◽

...

Keyword(s):

Gastric Cancer ◽

Cox Regression ◽

Malignant Tumors ◽

Prognostic Significance ◽

Gastric Cancer Tissue ◽

Expression Level ◽

Cancer Tissue ◽

Depth Of Invasion ◽

Human Gastric Cancer ◽

Cox Regression Analysis

Introduction: ACP5 plays crucial roles in multiple pathological processes, including the genesis and progression of malignant tumors. We performed this study with the purpose of determining whether ACP5 is a crucial biomarker significantly related with prognoses of gastric cancer (GC) patients. Methods: The expression level of ACP5 level was assessed among 170 gastric cancer specimens using immunohistochemistry (IHC). The associations between ACP5 expression and clinicopathological variables were evaluated. Univariate and multivariate Cox regression analyses were performed to confirm independent prognostic factors for GC patients. Results: It was revealed that ACP5 expression level in gastric cancer tissue was significantly associated with depth of invasion (P=0.029), and TNM stage (P=0.036). ACP5 was demonstrated by multivariate Cox regression analysis to be an independent prognostic factor for overall survival (OS) (P=0.001) and recurrence-free survival (RFS) (P=0.011) of GC patients. Conclusions: The expression of ACP5 in GC tissue was significantly higher than that in normal tissues and its overexpression was associated with a poorer prognosis, suggesting its potential roles in preventing and treating GC.

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Identification and Validation of the Immune Regulator CXCR4 as a Novel Promising Target for Gastric Cancer

Frontiers in Immunology ◽

10.3389/fimmu.2021.702615 ◽

2021 ◽

Vol 12 ◽

Author(s):

Shuai Xue ◽

Ming Ma ◽

Songhua Bei ◽

Fan Li ◽

Chenqu Wu ◽

...

Keyword(s):

Gastric Cancer ◽

Regression Analysis ◽

Cancer Patients ◽

Cox Regression ◽

Malignant Tumors ◽

Univariate Analysis ◽

Prognostic Indicator ◽

Migration And Invasion ◽

Cox Regression Analysis ◽

Gastric Cancer Patients

Immune checkpoint blockade has attracted a lot of attention in the treatment of human malignant tumors. We are trying to establish a prognostic model of gastric cancer (GC) based on the expression profile of immunoregulatory factor-related genes. Based on the TCGA database, we identified 234 differentially expressed immunoregulatory factors. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) conducted enrichment analysis to clarify the biological functions of differential expression of immunoregulatory factors. STRING database predicted the interaction network between 234 differently expressed immune regulatory factors. The expression of 11 immunoregulatory factors was significantly related to the overall survival of gastric cancer patients. Univariate Cox regression analysis, Kaplan–Meier analysis and multivariate Cox regression analysis found that immunomodulatory factors were involved in the progression of gastric cancer and promising biomarkers for predicting prognosis. Among them, CXCR4 was related to the low survival of GC patients and a key immunomodulatory factor in GC. Based on TCGA data, the high expression of CXCR4 in GC was positively correlated with the advanced stage and grade of gastric cancer and related to poor prognosis. Univariate analysis and multivariate analysis indicated that CXCR4 was an independent prognostic indicator for TCGA gastric cancer patients. In vitro functional studies had shown that CXCR4 promoted the proliferation, migration, and invasion of gastric cancer cells. In summary, this study has determined the prognostic value of 11 immunomodulatory factors in gastric cancer. CXCR4 is an independent prognostic indicator for gastric cancer patients, which may help to improve the individualized prognostic prediction of GC and provide candidates for the diagnosis and treatment of GC.

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Systemic Immune-Inflammation Index as a Prognostic Marker of Late Recurrence in Operable Gastric Cancer: A Dual Center Study

10.21203/rs.3.rs-1042125/v1 ◽

2021 ◽

Author(s):

Emre Yekedüz ◽

İzzet Doğan ◽

Dılşa Mızrak Kaya ◽

İlker Özgür ◽

Güngör Utkan ◽

...

Keyword(s):

Gastric Cancer ◽

Prognostic Factor ◽

Cox Regression ◽

Multivariable Analysis ◽

Late Recurrence ◽

Independent Prognostic Factor ◽

Operating Characteristics ◽

Cox Regression Analysis ◽

Immune Inflammation ◽

Recurrence Group

Abstract Aim To evaluate the prognostic role of the systemic immune-inflammation index (SII) in patients with operable gastric cancer. Methods We assessed 354 patients with operable gastric cancer from tertiary centers in Turkey. SII was calculated by following formula: [neutrophil (cellsx109/L) x platelet (cellsx109/L)] / lymphocyte (cellsx109/L). The best cut-off value for SII was determined by using “receiver operating characteristics (ROC)” analysis. We used log-rank and Cox-regression analysis for survival analyses. Results One hundred twenty patients were in the late recurrence group (recurrences have developed 36 months after the surgery). SII was not a prognostic factor in the early recurrence group. However, relapse-free survival (RFS) was longer in SII-low patients than SII-high patients in the late recurrence group. In multivariable analysis, SII was the only independent prognostic factor for RFS in the late recurrence group (Hazard Ratio (HR): 5.42, 95% CI:1.18-24.82, p=0.03). Conclusion SII was an independent prognostic factor for RFS in GC patients with late recurrence. Late recurrence risk was higher in SII-high patients than SII-low patients. Inflammation contributes to tumor progression, invasion, and metastasis. Prolonged exposure to chronic inflammation could explain the results of this study.

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Upregulation of FGD6 Predicts Poor Prognosis in Gastric Cancer

Frontiers in Medicine ◽

10.3389/fmed.2021.672595 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jianmin Zeng ◽

Man Li ◽

Huasheng Shi ◽

Jianhui Guo

Keyword(s):

Gastric Cancer ◽

Regression Analysis ◽

Prognostic Factor ◽

Poor Prognosis ◽

Cox Regression ◽

Independent Prognostic Factor ◽

Gene Set Enrichment Analysis ◽

High Expression ◽

Cox Regression Analysis ◽

The Relationship

Background: The aim of this study was to investigate the prognostic significance of faciogenital dysplasia 6 (FGD6) in gastric cancer (GC).Methods: The data of GC patients from The Cancer Genome Atlas (TCGA) database were used for the primary study. Then, our data were validated by the GEO database and RuiJin cohort. The relationship between the FGD6 level and various clinicopathological features was analyzed by logistic regression and univariate Cox regression. Multivariate Cox regression analysis was used to evaluate whether FGD6 was an independent prognostic factor for survival of patients with GC. The relationship between FGD6 and overall survival time was explored by the Kaplan–Meier method. In addition, gene set enrichment analysis (GSEA) was performed to investigate the possible biological processes of FGD6.Results: The FGD6 level was significantly overexpressed in GC tissues, compared with adjacent normal tissues. The high expression of FGD6 was related to a high histological grade, stage, and T classification and poor prognosis of GC. Multivariate Cox regression analysis showed that FGD6 was an independent prognostic factor for survival of patients with GC. GSEA identified that the high expression of FGD6 was mainly enriched in regulation of actin cytoskeleton.Conclusion: FGD6 may be a prognostic biomarker for predicting the outcome of patients with GC.

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The prognostic and diagnostic significance of the neutrophil-to-lymphocyte ratio in hepatocellular carcinoma: a prospective controlled study

British Journal of Cancer ◽

10.1038/s41416-021-01445-3 ◽

2021 ◽

Author(s):

Philip J. Johnson ◽

Sofi Dhanaraj ◽

Sarah Berhane ◽

Laura Bonnett ◽

Yuk Ting Ma

Keyword(s):

Hepatocellular Carcinoma ◽

Regression Analysis ◽

Prognostic Factor ◽

Cox Regression ◽

Prognostic Models ◽

Controlled Study ◽

Cox Regression Analysis ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Significant Difference

Abstract Background The neutrophil–lymphocyte ratio (NLR), a presumed measure of the balance between neutrophil-associated pro-tumour inflammation and lymphocyte-dependent antitumour immune function, has been suggested as a prognostic factor for several cancers, including hepatocellular carcinoma (HCC). Methods In this study, a prospectively accrued cohort of 781 patients (493 HCC and 288 chronic liver disease (CLD) without HCC) were followed-up for more than 6 years. NLR levels between HCC and CLD patients were compared, and the effect of baseline NLR on overall survival amongst HCC patients was assessed via multivariable Cox regression analysis. Results On entry into the study (‘baseline’), there was no clinically significant difference in the NLR values between CLD and HCC patients. Amongst HCC patients, NLR levels closest to last visit/death were significantly higher compared to baseline. Multivariable Cox regression analysis showed that NLR was an independent prognostic factor, even after adjustment for the HCC stage. Conclusion NLR is a significant independent factor influencing survival in HCC patients, hence offering an additional dimension in prognostic models.

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Identification of the angiogenesis related genes for predicting prognosis of patients with gastric cancer

BMC Gastroenterology ◽

10.1186/s12876-021-01734-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sheng Zheng ◽

Zizhen Zhang ◽

Ning Ding ◽

Jiawei Sun ◽

Yifeng Lin ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

High Efficiency ◽

Cox Regression ◽

Risk Group ◽

The Cancer Genome Atlas ◽

Differentially Expressed ◽

Lasso Regression ◽

Sequencing Data ◽

Cox Regression Analysis

Abstract Introduction Angiogenesis is a key factor in promoting tumor growth, invasion and metastasis. In this study we aimed to investigate the prognostic value of angiogenesis-related genes (ARGs) in gastric cancer (GC). Methods mRNA sequencing data with clinical information of GC were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The differentially expressed ARGs between normal and tumor tissues were analyzed by limma package, and then prognosis‑associated genes were screened using Cox regression analysis. Nine angiogenesis genes were identified as crucially related to the overall survival (OS) of patients through least absolute shrinkage and selection operator (LASSO) regression. The prognostic model and corresponding nomograms were establish based on 9 ARGs and verified in in both TCGA and GEO GC cohorts respectively. Results Eighty-five differentially expressed ARGs and their enriched pathways were confirmed. Significant enrichment analysis revealed that ARGs-related signaling pathway genes were highly related to tumor angiogenesis development. Kaplan–Meier analysis revealed that patients in the high-risk group had worse OS rates compared with the low-risk group in training cohort and validation cohort. In addition, RS had a good prognostic effect on GC patients with different clinical features, especially those with advanced GC. Besides, the calibration curves verified fine concordance between the nomogram prediction model and actual observation. Conclusions We developed a nine gene signature related to the angiogenesis that can predict overall survival for GC. It’s assumed to be a valuable prognosis model with high efficiency, providing new perspectives in targeted therapy.

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