scholarly journals Clinicopathologic Features Predicting HER2 Overexpression in Gastric Cancer

2013 ◽  
Vol 24 ◽  
pp. ix15
Author(s):  
J.S. Park ◽  
S. Lim ◽  
H.J. Chon ◽  
M.H. Hong ◽  
B. Kang ◽  
...  
2014 ◽  
Vol 146 (5) ◽  
pp. S-515 ◽  
Author(s):  
Jiong Shi ◽  
Qi Sun ◽  
Huiping Yu ◽  
YiFen Zhang ◽  
Cheng Fang ◽  
...  

2020 ◽  
Author(s):  
Junqing Wang ◽  
Fengjie Hao ◽  
Yuchen Yang ◽  
Xiaochun Fei ◽  
Xunhua Chen

Abstract Background Advanced gastric cancer (GC) induces diamal prognosis and high mortality. Discovery of new biomarkers or differentially expressed genes (DEGs) is serving for early diagnosis, prevention and therapautic treatmen in GC. In this study, by combining with biostatistics analysis, we aimed to verify the aberrant high expression and enhancing effects of SPP1 on GC, and to explore the probable relative post-transcriptional regulation. Methods Three datasets (GSE13911, GSE19826 and GSE27342) from NCBI GEO database were explored. SPP1 was screened out and detected in 105 real GC patients through immunohistochemistry analysis and RT-qPCR assay. The patients’ clinicopathologic features were collected and analyzed. The expression of SPP1 was examinated in three GC cell lines (MKN-45, AGS and SNU-16) . MKN-45 cell model with SPP1 depletd was constrcted through shRNA transfection. CCK8 assay, cell cycle detection and apoptosis rate calculation were conducted to evaluate the ability of cell growth. MiR-4262 was filtered out as a potential up-streaming regulator of SPP1 mRNA through bioinformatic prediction, and the dual-luciferase reporter assay was used for validation. Rescue experiment was introduced to confirm the post-transcriptional regulation. Results Thirteen DEGs increased in GC were selected, among which SPP1 was screened out for its significant over-expression in GC. SPP1 expression profile was validated in both the 105 real GC patients’ samples and three GC cell liens. High SPP1 expression was found significantly associated with the patients’ clinicopathologic features related to unideal prognosis, including tumor size, lymph node metastasis, local invasion grade and TNM stage. Depletion of SPP1 remarkably suppressed the GC cell growth. Whilst, microRNA-4262 was validated directly binding to the 3’-UTR of SPP1 mRNA in GC cells, degenerating the expression of SPP1. Conclusions SPP1 probably functions as an oncogenic gene in GC, and provides us a new biomarker in GC hopeful to promote GC prevention, diagnose and therapeutic treatment.


2016 ◽  
Vol 42 (9) ◽  
pp. S184
Author(s):  
M. Ciesielski ◽  
M. Szajewski ◽  
W.J. Kruszewski ◽  
R. Pęksa ◽  
J. Zieliński ◽  
...  

2013 ◽  
Vol 62 (1) ◽  
pp. 27 ◽  
Author(s):  
Hyun Jung Bok ◽  
Jin Ha Lee ◽  
Jae Kook Shin ◽  
Soung Min Jeon ◽  
Jae Jun Park ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-23
Author(s):  
Xiangchou Yang ◽  
Liping Chen ◽  
Yuting Mao ◽  
Zijing Hu ◽  
Muqing He

The role of an extracellular matrix- (ECM-) receptor interaction signature has not been fully clarified in gastric cancer. This study performed comprehensive analyses on the differentially expressed ECM-related genes, clinicopathologic features, and prognostic application in gastric cancer. The differentially expressed genes between tumorous and matched normal tissues in The Cancer Genome Atlas (TCGA) and validation cohorts were identified by a paired t -test. Consensus clusters were built to find the correlation between clinicopathologic features and subclusters. Then, the least absolute shrinkage and selection operator (lasso) method was used to construct a risk score model. Correlation analyses were made to reveal the relation between risk score-stratified subgroups and clinicopathologic features or significant signatures. In TCGA (26 pairs) and validation cohort (134 pairs), 25 ECM-related genes were significantly highly expressed and 11 genes were downexpressed in gastric cancer. ECM-based subclusters were slightly related to clinicopathologic features. We constructed a risk score model = 0.081 ∗ log 2   CD 36 + 0.043 ∗ log 2   COL 5 A 2 + 0.001 ∗ log 2   ITGB 5 + 0.039 ∗ log 2   SDC 2 + 0.135 ∗ log 2   SV 2 B + 0.012 ∗ log 2   THBS 1 + 0.068 ∗ log 2   VTN + 0.023 ∗ log 2   VWF . The risk score model could well predict the outcome of patients with gastric cancer in both training ( n = 351 , HR: 1.807, 95% CI: 1.292-2.528, P = 0.00046 ) and validation ( n = 300 , HR: 1.866, 95% CI: 1.347-2.584, P = 0.00014 ) cohorts. Besides, risk score-based subgroups were associated with angiogenesis, cell adhesion molecules, complement and coagulation cascades, TGF-beta signaling, and mismatch repair-relevant signatures ( P < 0.0001 ). By univariate (1.845, 95% CI: 1.382-2.462, P < 0.001 ) and multivariate (1.756, 95% CI: 1.284-2.402, P < 0.001 ) analyses, we regarded the risk score as an independent risk factor in gastric cancer. Our findings revealed that ECM compositions became accomplices in the tumorigenesis, progression, and poor survival of gastric cancer.


2020 ◽  
Vol 27 (3) ◽  
pp. 864
Author(s):  
Orhan Uzun ◽  
Aziz Senger ◽  
Mürsit Dincer ◽  
Erdal Polat ◽  
Mustafa Duman ◽  
...  

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 48-48 ◽  
Author(s):  
Johanna Lahdenranta ◽  
Violette Paragas ◽  
Arthur J. Kudla ◽  
Ryan Overland ◽  
Victor M. Moyo ◽  
...  

48 Background: ErbB2 (HER2) overexpression has been reported in 7-34% of gastric cancers. ErbB3 (HER3) is the preferred dimerization partner of ErbB2, and ErbB2/ErbB3 heterodimer activation is implicated in the progression and metastasis of ErbB2+ tumors. Activation of ErbB3 signaling is a postulated resistance mechanism to current ErbB2-directed therapies and select chemotherapies. In line with this research, ErbB3 levels are associated with poor prognosis in gastric cancers. MM-111 is a bi-specific antibody that docks to ErbB2 and inhibits ErbB3 signaling in cells that overexpress ErbB2. In this study, MM-111 was evaluated in ErbB2+ gastric cancer by testing the activity of MM-111 in ErbB2+ pre-clinical models of gastric cancer, and by assessing the prevalence of potentially predictive biomarkers in a panel of archived gastric and gastroesophageal junction (GEJ) tumors. Methods: MM-111 was tested in ErbB2+ gastric cancer xenografts that were either untreated or after tumors ceased to respond to trastuzumab/5-FU. Xenografts were analyzed at multiple time points for the expression of ErbB-receptor family members and their downstream signaling by Luminex -assays. Preclinical data indicate that ErbB2, ErbB3, and heregulin are predictive biomarkers for MM-111. In order to determine the prevalence of our potentially predictive biomarkers in gastric and GEJ cancers, we obtained commercially archived tumor tissue and assayed the tissue for ErbB2 and ErbB3 expression levels using quantitative IHC, and measured heregulin transcript levels by RT-PCR. Results: MM-111 synergizes with various treatment regimens in the 2nd line treatment setting in ErbB2+ gastric cancer xenografts. In our models, the combination of MM-111, trastuzumab, and paclitaxel is particularly effective after tumors progressed on trastuzumab/5-FU. MM-111 inhibits the activity of the ErbB –signaling axis in these models. In addition, 23% of GEJ tumor samples and 20% of gastric samples were positive for potentially predictive biomarkers. Conclusions: ErbB2+xenograft tumors that stop responding to trastuzumab-based therapies benefit from MM-111–based regimens.


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