scholarly journals RhoA, Claudin 18, and c-MET in Gastric Cancer: Clinicopathological Characteristics and Prognostic Significance in Curative Resected Patients

2021 ◽  
Vol 10 (1) ◽  
pp. 4
Author(s):  
Marina Alessandra Pereira ◽  
Marcus Fernando Kodama Pertille Ramos ◽  
Andre Roncon Dias ◽  
Leonardo Cardili ◽  
Renan Ribeiro e Ribeiro ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Inflammatory Infiltrate ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Venous Invasion ◽  
Molecular Classification ◽  
Clinicopathological Characteristics ◽  
Curative Gastrectomy ◽  
Poorly Differentiated ◽  
Prediction Of Prognosis

Background: Recently, markers related to molecular classification were suggested as promising therapeutic targets for treatment and prediction of prognosis in gastric cancer (GC), including c-MET, RhoA, and Claudin-18 (CLDN18). This study aimed to investigate their expression in GC and its correlation with clinicopathological characteristics and survival. Methods: We retrospectively evaluated GC patients who underwent curative gastrectomy. c-MET, RhoA, and CLDN18 were analyzed through immunohistochemistry (IHC), and groups for analysis were determined according to the median values obtained for each marker. Results: Among the 349 GC evaluated, 180 (51.6%), 59 (16.9%), and 61 (17.5%) patients were completely negative for c-MET, RhoA, and CLDN18, respectively. Total gastrectomy, D1 lymphadenectomy, poorly differentiated histology, and greater inflammatory infiltrate were more frequent in the c-MET-negative group. Diffuse type, greater inflammatory infiltrate, and advanced pT and pTNM stage were associated with low-RhoA GC. The venous invasion was more frequent in the low-CLDN18 group. Furthermore, c-MET was positively correlated with RhoA and negatively with CLDN18. HER2 expression was associated with c-MET-positive and high-CLDN18 GC; and loss of E-cadherin expression in c-MET-negative and low-RhoA GC. c-MET-negative and Low-RhoA were significantly associated with worse disease-free survival. Conclusions: c-MET, RhoA, and CLD18 expression occurred frequently in GC. RhoA GC had distinct clinicopathological characteristics related to prognosis. c-MET and RhoA were associated with survival but were not independent predictors of prognosis.

Prognostic significance of ADAM17 expression in patients with gastric cancer who underwent curative gastrectomy.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 60-60
Author(s):  
Ahmet Bilici ◽  
Dincer Aydin ◽  
Dilek Yavuzer ◽  
Hatice Odabas ◽  
Ozlem Ercelep ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Multivariate Analysis ◽  
Molecular Marker ◽  
Cancer Progression ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Prognostic Indicator ◽  
Curative Gastrectomy ◽  
Prognostic Importance ◽  
Gastric Cancer Patients

60 Background: Tumor invasion and metastasis are complex processes, involving regulation at the molecular level of adhesive molecules, proteolitic enzymes, and cell growth and angiogenesis factors. A Disintegrin and Metalloproteinase (ADAM)17 has been indicated to be indispensable regulator of celular event from proliferation to migration.Although prognostic importance of ADAM17 expression has been investigated in several tumors, its clinical utility as a useful prognostic molecular marker remains unclearin gastric cancer.In the present study, we evaluated the expression of ADAM17 and its prognostic significance in gastric cancer patients after surgery. Methods: Prognostic significance of ADAM17 expression was analyzed by immunohistochemically in 158 patients with gastric cancer and the relationship between its expression and clinicopathological factors was also evaluated. Results: High expression of ADAM17 was detected in 81 patients(51%),while low expression was found in 77 cases (49%). There was significant correlation between gender, histology, lymph node metastasis, vascular invasion, the presence of recurrence and high ADAM17 expression. Recurrence in patients with high ADAM17 expression was significantly higher than that for patients with low ADAM17 expression(p=0.032). The median disease-free survival (DFS) time for patients with high ADAM17 expressed tumors were worse than those of patients with low ADAM17 expressed tumor (16.6 vs. 44.2 months, p=0.004).In addition, patients with low ADAM17 expression had a higher median overall survival (OS)interval than those of high ADAM17 expressed patients (49.6 vs. 26.9 months, p=0.019). Multivariate analysis indicated that the rate of ADAM17 expression was an independent prognostic factor for DFS, in addition to known important clinicopathological prognostic indicator for DFS. But its' prognostic importance could not be proved by multivariate analysis for OS. Conclusions: The potential value of ADAM17 expression as a useful molecular marker in gastric cancer progression should be evaluated comprehensively,it may predict recurrence and poor prognosis in patients with gastric cancer after curative resection.

Prognostic significance of tumour infiltration growth pattern in patients with advanced gastric cancer

2018 ◽  
Vol 72 (2) ◽  
pp. 165-171 ◽  
Author(s):  
Bochao Zhao ◽  
Jiale Zhang ◽  
Di Mei ◽  
Xinyu Huang ◽  
Shihui Zou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Pattern ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Curative Gastrectomy ◽  
Japanese Classification ◽  
Node Metastases ◽  
Infiltration Growth ◽  
Tumour Infiltration ◽  
The Impact

AimsThe prognostic significance of infiltration growth pattern (INF) in patients with gastric cancer (GC) remains controversial. In the present study, we evaluated the impact of INF pattern on the prognosis of patients with advanced GC.MethodsA total of 1455 patients with advanced GC who underwent curative gastrectomy in our institution were retrospectively analysed. All patients were histopathologically classified as INFa/b and INFc pattern according to the Japanese Classification of Gastric Cancer. The prognostic difference between two patterns was compared and clinicopathological features were analysed.ResultsThe prognosis of the patients with INFc pattern was poorer than that of those with INFa/b pattern (5-year disease-free survival, INFa/b: 48.4% vs INFc: 33.5%, p < 0.001), even when they were stratified according to lymph node metastasis and the tumour, node, metastases stage. In addition, the subgroup analysis indicated that INFc pattern was significantly associated with poorer prognosis of T2–T3 stage patients (T2, INFa/b: 72.7% vs INFc: 55.4%; T3, INFa/b: 47.4% vs INFc: 33.5%; p<0.001). However, a similar result was not observed among T4a stage patients (INFa/b: 26.8% vs INFc: 24.8%, p>0.05). The prognosis of T2 stage patients with INFc pattern was similar to that of T3 stage patients with INFa/b pattern (p>0.05). Also, there was no significantly prognostic difference between T3 stage patients with INFc pattern and T4a stage patients (p>0.05). The multivariate analysis indicated that INF pattern was an independent prognostic factor for patients with advanced GC (HR 1.259, 95%CI 1.089 to 1.454).ConclusionIn view of its prognostic significance, histopathological evaluation of INF pattern in surgically resected specimens should be recommended in patients with advanced GC.

Genetic variants in miRNA machinery genes associated with clinicopathological characteristics and outcomes of gastric cancer patients

2018 ◽  
Vol 33 (3) ◽  
pp. 301-307 ◽  
Author(s):  
Yuqian Liao ◽  
Yulu Liao ◽  
Jun Li ◽  
Liyan Liu ◽  
Junyu Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Genetic Variants ◽  
Sex Differentiation ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
Lymph Node Status ◽  
T Stage ◽  
Poorly Differentiated ◽  
Gastric Cancer Patients

Background: Polymorphisms in miRNA machinery genes have been proved to be related to risk or survival of several kinds of cancers, but the results are controversial and the role of these polymorphisms in gastric cancer remains uncertain. In our study, we investigated the association between five genetic variants in miRNA machinery genes ( DICER, RAN, XPO5 [name of the gene]) and clinical outcomes in Chinese gastric cancer patients. Methods: A total of 96 patients with stage IB-III gastric cancer treated with radical gastrectomy and adjuvant chemotherapy of oxaliplatin and fluorouracils were analyzed. The MassARRAY MALDI-TOF system was used to determine the genotypes. Results: DICER rs3742330 AG+GG genotype was associated with more advanced T stage compared to AA genotype ( P=0.009). More patients with XPO5 rs2257082 CC genotype had poorly differentiated tumors compared with CT+TT genotype carriers. After adjustment by age, sex, differentiation, T stage, and lymph node status, XPO5 rs2257082 CC genotype carriers were found to have worse disease-free survival than CT+TT genotype carriers (adjusted HR 3.099; 95% CI 1.270, 7.564; P=0.013), carriers of RAN rs14035 CC genotype had higher three-year OS rate than carriers of CT+TT genotype (adjusted HR 3.174; 95% CI 1.010, 9.973; P=0.048). Conclusions: These results indicated that genetic variants in miRNA machinery genes might be associated with the clinicopathological features and prognosis of completely resected gastric cancer patients.

scholarly journals Evaluation of the prognostic value of CBXs in gastric cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mengya He ◽  
Limin Yue ◽  
Haiyan Wang ◽  
Feiyan Yu ◽  
Mingyang Yu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Target Genes ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Genetic Alterations ◽  
Genetic Mutation ◽  
The Cancer Genome Atlas ◽  
Normal Tissues ◽  
Interactive Analysis ◽  
Gastric Cancer Patients

AbstractChromobox (CBX) proteins were suggested to exert epigenetic regulatory and transcriptionally repressing effects on target genes and might play key roles in the carcinogenesis of a variety of carcinomas. Nevertheless, the functions and prognostic significance of CBXs in gastric cancer (GC) remain unclear. The current study investigated the roles of CBXs in the prognosis of GC using the Oncomine, The Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, The Cancer Genome Atlas (TCGA), and cBioPortal databases. CBX1/2/3/4/5 were significantly upregulated in GC tissues compared with normal tissues, and CBX7 was downregulated. Multivariate analysis showed that high mRNA expression levels of CBX3/8 were independent prognostic factors for prolonged OS in GC patients. In addition, the genetic mutation rate of CBXs was 37% in GC patients, and genetic alterations in CBXs showed no association with OS or disease-free survival (DFS) in GC patients. These results indicated that CBX3/8 can be prognostic biomarkers for the survival of GC patients.

Amplification and expression of c-MET correlate with poor prognosis of patients with gastric cancer and upregulate the expression of PDL1

2021 ◽  
Vol 53 (5) ◽  
pp. 547-557
Author(s):  
Ya’nan Yang ◽  
Chenchen Wang ◽  
Congqi Dai ◽  
Xinyang Liu ◽  
Wenhua Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Positive Association ◽  
Her2 Positive ◽  
Kaplan Meier ◽  
Met Amplification ◽  
Amplification Rate ◽  
Cox Proportional Hazard Regression

Abstract The prognostic significance of c-MET in gastric cancer (GC) remains uncertain. In the present study, we examined the amplification, expression, and the prognostic value of c-MET, human epidermal growth factor receptor 2 (HER2), and programmed cell death 1 ligand 1 (PDL1), together with the correlations among them in a large cohort of Chinese samples. A total of 444 patients were included. The immunohistochemistry (IHC) and the dual-color silver in situ hybridization (SISH) were performed to examine their expression and amplification. Univariate and multivariate analyses were performed by the Cox proportional hazard regression model, and survival curves were estimated by the Kaplan–Meier method. The positivity determined by IHC of c-MET was 24.8%, and the MET amplification rate was 2.3%. The positivity rates of HER2 and PDL1 were 8% and 34.7%, respectively. PDL1 expression had a significantly positive association with c-MET expression. c-MET positivity played a significant prognostic role in disease-free survival (DFS) (P = 0.032). Patients with mesenchymal-epithelial transition (MET) amplification had significantly poorer prognosis on both DFS and overall survival (OS). Subgroup analysis showed that in HER2-negative patients, but not in HER2-positive patients, MET-positive patients had significantly worse DFS (P = 0.000) and OS (P = 0.006). c-MET regulated the expression of PDL1 through an AKT-dependent pathway. c-MET inhibitor enhanced the T-cell killing ability and increased the efficacy of PD1 antibody. c-MET was found to be an independent prognostic factor for DFS of GC patients. A combination of c-MET inhibitors and PD1 antibodies could enhance the killing capacity of T cells, providing a preliminary basis for the clinical research on the same combination in GC treatment.

scholarly journals HER-2 Expression in Immunohistochemistry Has No Prognostic Significance in Gastric Cancer Patients

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Agnieszka Halon ◽  
Piotr Donizy ◽  
Przemyslaw Biecek ◽  
Julia Rudno-Rudzinska ◽  
Wojciech Kielan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Test Score ◽  
Prognostic Significance ◽  
Clinicopathological Parameters ◽  
Prognostic Impact ◽  
Curative Surgery ◽  
Regional Lymph Nodes ◽  
Poorly Differentiated ◽  
Her 2 ◽  
Gastric Cancer Patients

The role of HER-2 expression as a prognostic factor in gastric cancer (GC) is still controversial. The aim of the study was to asses HER-2 status, its correlations with clinicopathological parameters, and prognostic impact in GC patients. Tumor samples were collected from 78 patients who had undergone curative surgery. In order to evaluate the intensity of immunohistochemical (IHC) reactions two scales were applied: the immunoreactive score according to Remmele modified by the authors and standardised Hercep test score modified for GC by Hofmann et al. The HER-2 overexpression was detected by IHC in 23 (29.5%) tumors in Hercep test (score 2+/3+) and in 24 (30.7%) in IRS scale (IRS 4–12). The overexpression of HER-2 was associated with poorly differentiated tumors, but this correlation was not significant (P=0.064). No relationship was found between HER-2 expression and primary tumor size and degree of spread to regional lymph nodes. Both univariate and multivariate analyses revealed that TNM stage and patient’s age were the crucial negative prognostic factors. No correlation was observed between patient survival and expression of HER-2 estimated using both scales. This research did not confirm HER-2 expression (evaluated with immunohistochemistry) value as a prognostic tool in GC.

scholarly journals HER2 and BRAF mutation in colorectal cancer patients: a retrospective study in Eastern China

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8602 ◽  
Author(s):  
Xiangyan Zhang ◽  
Jie Wu ◽  
Lili Wang ◽  
Han Zhao ◽  
Hong Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Eastern China ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Molecular Classification ◽  
Clinicopathological Characteristics ◽  
Stage I ◽  
Chinese Patients ◽  
Poor Differentiation ◽  
Colorectal Cancer Patients

Objective To investigate the frequency and prognostic role of the human epidermal growth factor receptor 2 gene (HER2) and BRAF V600E gene mutation in Chinese patients with colorectal cancer (CRC). Methods Clinicopathological and survival information from 480 patients with stage I–III CRC were reviewed and recorded. HER2 amplification was analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), BRAF V600E mutation was tested by IHC and Sanger sequencing. The relationship between HER2 and BRAF V600E mutation status and clinicopathological characteristics and outcomes were determined. Results The amplification of HER2 and BRAF V600E mutation were identified in 27 of 480 (5.63%) and 19 of 480 (3.96%) CRC patients, respectively. HER2 amplification significantly correlated with greater bowel wall invasion (P = 0.041) and more advanced TNM stage (I vs. II vs. III; 0 vs 5.78% vs. 7.41%, P = 0.013). Patients suffering from tumors with poor differentiation had a higher incidence rate of BRAF V600E mutation than those with moderate/well differentiation (7.77% vs 2.92%, P = 0.04). HER2 amplification was an independent prognostic factor for worse disease-free survival (DFS) (HR = 2.53, 95% CI: 1.21–5.30, P = 0.014). Conclusion The prevalence of HER2 amplification and BRAF V600E mutation in stage I–III CRC patients in Chinese was 6% and 4%, respectively, and HER2 amplification appeared to be associated with a worse DFS. More comprehensive molecular classification and survival analysis are needed to validate our findings.

scholarly journals Krüppel-Like Factor 7 is a Marker of Aggressive Gastric Cancer and Poor Prognosis

2017 ◽  
Vol 43 (3) ◽  
pp. 1090-1099 ◽  
Author(s):  
Zhonghua Jiang ◽  
Tingting Yu ◽  
Zhining Fan ◽  
Hongmei Yang ◽  
Xin Lin
Keyword(s):  
Gastric Cancer ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
Strong Negative Correlation ◽  
Functional Studies ◽  
Expression Of Genes ◽  
Cancer Genome Atlas

Background/Aims: Krüppel-like factor (KLF) 7 protein is a member of the KLF transcription factor family, which plays important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation and metabolism. However, the role of KLF7 in gastric cancer (GC) is unknown. The aim of this study is to explore the role of KLF7 in GC and its correlation with clinicopathological characteristics and prognosis of GC patients. Methods: We first systematically evaluated dysregulation of the KLF family in The Cancer Genome Atlas (TCGA) GC database. Then, 252 patients who underwent surgery for GC were enrolled to validate the results from the TCGA. Functional studies were also used to explore the role of KLF7 in GC. Results: In the TCGA database, we found that KLF7 was an independent predictor for survival by both univariate and multivariate analysis (P<0.05). In a validation cohort, KLF7 expression was significantly increased in GC tissues compared with adjacent normal controls (P=0.013). High KLF7 expression correlated with inferior prognostic factors, such as T stage (P=0.022), N stage (P =0.005) and lymphovascular invasion (P=0.009). Furthermore, we observed a strong negative correlation between KLF7 expression and 5-year overall survival and disease-free survival in GC patients (P<0.05). Moreover, our in vitro studies showed a notable decrease in migration in KLF7 knockdown cells. Conclusion: KLF7 has an important role in GC progression, as it inhibits GC cell migration and may serve as a prognostic marker.

Prognostic Significance of Pre- and Postoperative Lymphocyte Counts in Patients with Gastric Cancer

2018 ◽  
Vol 36 (2) ◽  
pp. 137-143 ◽  
Author(s):  
Hiroaki Saito ◽  
Yusuke Kono ◽  
Yuki Murakami ◽  
Yuji Shishido ◽  
Hirohiko Kuroda ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Elderly Patients ◽  
Lymphocyte Count ◽  
Operating Characteristic ◽  
Survival Rates ◽  
Prognostic Significance ◽  
Venous Invasion ◽  
Prognostic Indicator ◽  
Characteristic Analysis ◽  
Patient Prognosis

Background: Although preoperative lymphopenia is reportedly a prognostic factor in cancer patients, the association between postoperative lymphopenia and patient prognosis has not been widely studied. Methods: We enrolled 352 patients who underwent surgery for gastric cancer (GC) between January 2005 and April 2013 to analyze correlations among pre- and postoperative lymphocyte counts (LCs) and prognosis in GC patients. Results: Pre- and postoperative (obtained 1 day after surgery) LCs were significantly correlated (r = 0.496, p < 0.0001). Pre- and postoperative LCs of elderly patients were significantly lower than those of non-elderly patients. Postoperative lymphocyte count was significantly lower in patients with a differentiated tumor than in those with an undifferentiated tumor. Based on the results of receiver operating characteristic analysis, patients were classified into subgroups as: preoperative LC ≥1,676 (pre-LCHigh), preoperative LC <1,676 (pre-LCLow); and as postoperative LC ≥855 (post-LCHigh), and postoperative LC <855 (post-LCLow). Five-year overall survival rates significantly differed between pre-LCHigh (82.5%) and pre-LCLow (71.6%) groups (p = 0.023); and also between the post-LCHigh (81.5%) and post-LCLow (69.5%) groups (p = 0.0072). The 5-year disease specific survival rates were 91.3 and 82.4% in patients with post-LCHigh and those with post-LCLow, respectively, and differences were statistically significant (p = 0.015). Multivariate analysis indicated that postoperative lymphocyte count was an independent prognostic indicator, along with age, gender, tumor size, lymph node metastasis, and venous invasion. Conclusions: Postoperative lymphocyte count is a useful predictive factor for prognosis in GC patients.

scholarly journals Claudin-1 Is a Valuable Prognostic Biomarker in Colorectal Cancer: A Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Didi Zuo ◽  
Jiantao Zhang ◽  
Tao Liu ◽  
Chao Li ◽  
Guang Ning
Keyword(s):  
Colorectal Cancer ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Venous Invasion ◽  
Lymphatic Invasion ◽  
Cochrane Library ◽  
Test Sequence ◽  
Tumor Type ◽  
The Stability

Background. Claudin-1 plays an important part in maintaining the mucosal structures and physiological functions. Several studies showed a relationship between claudin-1 and colorectal cancer (CRC), but its prognostic significance is inconsistent. This meta-analysis assessed the prognostic value and clinical significance of claudin-1 in CRC. Materials and Methods. We retrieved eligible studies from PubMed, Cochrane Library, Embase, and Web of Science databases before February 10, 2020. The hazard ratio (HR) with 95% confidence interval (CI) was applied to assess the correlation between claudin-1 and prognosis and clinical features. Heterogeneity was assessed by the Cochran Q test and I-square (I2), while publication bias was evaluated by the Begg test and Egger test. Test sequence analysis (TSA) was used to estimate whether the included studies’ number is sufficient. The stability of the results was judged by sensitivity analysis. Metaregression was utilized to explore the possible covariance which may impact on heterogeneity among studies. Results. Eight studies incorporating 1704 patients met the inclusion criteria. Meta-analysis showed that the high expression of claudin-1 was associated with better overall survival (HR, 0.46; 95% CI, 0.28–0.76; P=0.002) and disease-free survival (HR, 0.44; 95% CI, 0.29–0.65; P=0.003) in CRC. In addition, we found that claudin-1 was related to the better tumor type (n=6; RR, 0.60; 95% CI, 0.49–0.73; P<0.00001), negative venous invasion (n=4; RR, 0.81; 95% CI, 0.70–0.95; P=0.001), and negative lymphatic invasion (n=4; RR, 0.83; 95% CI, 0.74–0.92; P=0.0009). Conclusion. The increased claudin-1 expression in CRC is associated with better prognosis. In addition, claudin-1 was related to the better tumor type and the less venous invasion and lymphatic invasion.

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