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

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.

Effect of combined consideration of distinct signatures of VEGF and soluble VEGFR2 on prognostic implication in gastric cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 56-56
Author(s):  
Chan-Young Ock ◽  
Ah-Rong Nam ◽  
Ju-Hee Bang ◽  
Tae-Yong Kim ◽  
Kyung-Hun Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Regression Analysis ◽  
Growth Factor ◽  
Cox Regression ◽  
Linear Regression Analysis ◽  
Vegf Receptor ◽  
Prognostic Impact ◽  
Prognostic Implication ◽  
Cox Regression Analysis ◽  
Fibroblast Growth Factor Basic

56 Background: Anti-angiogenic strategy in gastric cancer (GC) has been highlighted again due to the recent success of ramucirumab and apatinib. Therefore, the comprehensive network of VEGF, soluble VEGF receptor-2 (sVEGFR2) and cytokines and other angiogenic factors (CAF) in GC and their prognostic impact would be of importance, although they have been poorly understood. We aimed to find out the CAF signature associated with VEGF and sVEGFR2, and to explore their prognostic implication in GC. Methods: We measured pretreatment serum levels of 52 CAFs, including VEGF and sVEGFR2, using multiplex bead immunoassays and ELISA, in 70 patients who were diagnosed with GC in Seoul National University Hospital, and treated with palliative chemotherapy. Linear regression analysis for correlating CAFs with VEGF and sVEGFR2, and survival analysis by log rank test and Cox regression analysis were performed. Results: The VEGF signature was shown to be associated with seven CAFs (interluekin [IL]-7, IL-12p70, IL-2Ra, IL-10, stem cell factor, Fibroblast growth factor-basic, IL-3). The sVEGFR2 signature was associated with IL-4 and platelet-derived growth factor beta, but VEGF and sVEGFR2 showed no association with each other. Patients with high VEGF had a tendency to have worse overall survival (OS) than those with low VEGF (11.2 months versus 16.7 months; P = 0.061). However, among patients with high-sVEGFR2, OS was not different according to VEGF (12.1 months, high-VEGF versus 15.1 months, low-VEGF; P = 0.546). Interestingly, the poor prognostic impact of high-VEGF was far significant in patients with low-sVEGFR2 (10.9 months versus 16.8 months; P = 0.036). With this perspective, VEGF/sVEGFR2 ratio was significantly correlated with worse OS in univariate as well as multivariate analysis (HR 1.78 [95% CI 1.08-2.94], P= 0.024). Conclusions: Based on the comprehensive network analysis of CAF, VEGF and sVEGFR2 had distinct CAF signatures in GC. Consideration of both VEGF and sVEGFR2 confers more accurate prognostic implication compared with VEGF alone in GC. Regarding the angiogenic aspect, VEGF/sVEGFR2 ratio is significantly correlated with survival outcome in GC.

scholarly journals P2X7R as an independent prognostic indicator in gastric cancer

2020 ◽  
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.

scholarly journals Prognostic Significance of ACP5 in Human Gastric Cancer

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.

scholarly journals High Expression of PABPC1 Predicts Worse Survival of Gastric Cancer Patients

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.

scholarly journals TBL1XR1 Is Highly Expressed in Gastric Cancer and Predicts Poor Prognosis

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Fang Liu ◽  
Yuan He ◽  
Qinghua Cao ◽  
Ni Liu ◽  
Wenhui Zhang
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Cox Regression ◽  
Biological Significance ◽  
High Expression ◽  
Human Gastric Cancer ◽  
Mrna Levels ◽  
Poor Overall Survival ◽  
Cox Regression Analysis

Objective. To investigate the expression of transducin- (β-) like 1 X-linked receptor 1 (TBL1XR1) in human gastric cancer (GC) and its correlation with prognostic and biologic significance.Methods. TBL1XR1 mRNA expression was analyzed in gastric cancer using a microarray dataset (GSE2701) from the Gene Expression Omnibus (GEO). Immunohistochemistry (IHC) analysis of TBL1XR1 was performed on GC tissue microarray (TMA) to assess its prognostic and biological significance in 334 patients of GC.Results. Analysis of GSE2701 showed that the mRNA levels of TBL1XR1 were significantly elevated in primary gastric tumor and lymph node tissues than normal gastric tissues (P<0.05). The same results of TBL1XR1 protein level were observed by IHC staining in 334 GC tissues. 204 of 334 (60.1%) primary gastric cancer tissues showed high expression of TBL1XR1 protein. TBL1XR1 overexpression was significantly correlated with lymph node metastasis (P=0.000) and advanced TNM stage (P=0.001). Moreover, high levels of TBL1XR1 predicted worse overall survival (P=0.015). Multivariate Cox regression analysis indicated that high expression of TBL1XR1 was an independent prognostic factor for poor overall survival (HR, 0.525; 95% confidence interval, 0.367–0.752;P=0.005).Conclusion. This present study demonstrates that TBL1XR1 is overexpressed in gastric cancer and may be a potential predictor and therapeutic target for GC patients.

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

1997 ◽  
Vol 15 (2) ◽  
pp. 816-825 ◽  
Author(s):  
S Nakamori ◽  
H Furukawa ◽  
M Hiratsuka ◽  
T Iwanaga ◽  
S Imaoka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Intensive Therapy ◽  
Antigen Expression ◽  
Prognostic Indicator ◽  
Depth Of Invasion ◽  
Altered Expression ◽  
Cox Regression Analysis ◽  
Clinicopathologic Factors

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.

scholarly journals m6A Methylation Mediates LHPP Acetylation as a Tumour Aerobic Glycolysis Suppressor to Improve the Prognosis of Gastric Cancer

2021 ◽  
Author(s):  
Jian-Xian Lin ◽  
Ning-Zi Lian ◽  
You-Xin Gao ◽  
Qing-Zhu Qiu ◽  
Hua-Gen Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cox Regression ◽  
Aerobic Glycolysis ◽  
Prognostic Significance ◽  
Predictive Biomarker ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Cox Regression Analysis

Abstract BackgroundLHPP, a histidine phosphatase, has been implicated in tumor progression. However, its role, underlying mechanisms, and prognostic significance in human gastric cancer (GC) are elusive. MethodsWe obtained GC tissues and corresponding normal tissues from 8 patients and identified LHPP as a downregulated gene via RNA-seq. qRT-PCR and western blotting were applied to examine LHPP levels in normal and GC tissues. The prognostic value of LHPP was elucidated using tissue microarray and IHC analyses in two independent GC cohorts. The functional roles and mechanistic insights of LHPP in GC growth and metastasis were evaluated in vitro and in vivo. ResultsThe results showed that LHPP expression was significantly decreased in GC tissues at both the mRNA and protein level. Multivariate Cox regression analysis revealed that LHPP was an independent prognostic factor and effective predictor in patients with GC. The low expression of LHPP was significantly related to the poor prognosis and chemotherapy sensitivity of gastric cancer patients. Moreover, elevated LHPP expression effectively suppressed GC growth and metastasis in vitro and in vivo. Mechanistically, the m6A modification of LHPP mRNA by METTL14 represses its expression; LHPP inhibits the phosphorylation of GSK3b through acetylation, and mediates HIF1A to inhibit glycolysis, proliferation, invasion and metastasis of gastric cancer cells. ConclusionLHPP is regulated by m6A methylation and regulates the metabolism of GC by changing the acetylation level. Thus, LHPP is a potential predictive biomarker and therapeutic target for GC.

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

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.

scholarly journals Impact of sarcopenia in advanced and metastatic soft tissue sarcoma

2021 ◽  
Author(s):  
Dennis Strassmann ◽  
Bennet Hensen ◽  
Viktor Grünwald ◽  
Katharina Stange ◽  
Hendrik Eggers ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Cox Regression ◽  
Therapy Response ◽  
Prognostic Impact ◽  
Patient Counseling ◽  
Skeletal Muscle Index ◽  
Prognostic Parameter ◽  
Dismal Prognosis ◽  
Metastatic Soft Tissue Sarcoma

Abstract Introduction Advanced or metastatic soft tissue sarcoma (a/mSTS) is associated with a dismal prognosis. Patient counseling on treatment aggressiveness is pivotal to avoid over- or undertreatment. Recently, evaluation of body composition markers like the skeletal muscle index (SMI) became focus of interest in a variety of cancers. This study focuses on the prognostic impact of SMI in a/mSTS, retrospectively. Methods 181 a/mSTS patients were identified, 89 were eligible due to prespecified criteria for SMI assessment. Baseline CT-Scans were analyzed using an institutional software solution. Sarcopenia defining cut-off values for the SMI were established by optimal fitting method. Primary end point was overall survival (OS) and secondary endpoints were progression free survival (PFS), disease control rate (DCR), overall response rate (ORR). Descriptive statistics as well as Kaplan Meier- and Cox regression analyses were administered. Results 28/89 a/mSTS patients showed sarcopenia. Sarcopenic patients were significantly older, generally tended to receive less multimodal therapies (62 vs. 57 years, P = 0.025; respectively median 2.5 vs. 4, P = 0.132) and showed a significantly lower median OS (4 months [95%CI 1.9–6.0] vs. 16 months [95%CI 8.8–23.2], Log-rank P = 0.002). Sarcopenia was identified as independent prognostic parameter of impaired OS (HR 2.40 [95%-CI 1.4–4.0], P < 0.001). Moreover, DCR of first palliative medical treatment was superior in non-sarcopenic patients (49.2% vs. 25%, P = 0.032). Conclusion This study identifies sarcopenia as a prognostic parameter in a/mSTS. Further on, the data suggest that sarcopenia shows a trend of being associated with first line therapy response. SMI is a promising prognostic parameter, which needs further validation.

Perioperative Activation of Disseminated Tumor Cells in Bone Marrow of Patients With Prostate Cancer

2009 ◽  
Vol 27 (10) ◽  
pp. 1549-1556 ◽  
Author(s):  
Dorothea Weckermann ◽  
Bernhard Polzer ◽  
Thomas Ragg ◽  
Andreas Blana ◽  
Günter Schlimok ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Tumor Cells ◽  
Cox Regression ◽  
Systemic Disease ◽  
Disseminated Tumor Cells ◽  
Comparative Genomic ◽  
Prognostic Impact ◽  
Primary Tumors ◽  
Cox Regression Analysis

Purpose The outcome of prostate cancer is highly unpredictable. To assess the dynamics of systemic disease and to identify patients at high risk for early relapse we followed the fate of disseminated tumor cells in bone marrow for up to 10 years and genetically analyzed such cells isolated at various stages of disease. Patients and Methods Nine hundred bone marrow aspirates from 384 patients were stained using the monoclonal antibody A45-B/B3 directed against cytokeratins 8, 18, and 19. Log-rank statistics and Cox regression analysis were applied to determine the prognostic impact of positive cells detected before surgery (244 patients) and postoperatively (214 patients). Samples from primary tumors (n = 55) and single disseminated tumor cells (n = 100) were analyzed by comparative genomic hybridization. Results Detection of cytokeratin-positive cells before surgery was the strongest independent risk factor for metastasis within 48 months (P < .001; relative risk [RR], 5.5; 95% CI, 2.4 to 12.9). In contrast, cytokeratin-positive cells detected 6 months to 10 years after radical prostatectomy were consistently present in bone marrow with a prevalence of approximately 20% but had no influence on disease outcome. Characteristic genotypes of cytokeratin-positive cells were selected at manifestation of metastasis. Conclusion Cytokeratin-positive cells in the bone marrow of prostate cancer patients are only prognostically relevant when detected before surgery. Because we could not identify significant genetic differences between pre- and postoperatively isolated tumor cells before manifestation of metastasis, we postulate the existence of perioperative stimuli that activate disseminated tumor cells. Patients with cytokeratin-positive cells in bone marrow before surgery may therefore benefit from adjuvant therapies.

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