scholarly journals Identification of the RP11-21C4.1/SVEP1 gene pair associated with FAT2 mutations as a potential biomarker in gastric cancer

Bioengineered ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 4361-4373
Author(s):  
Lingshan Zhou ◽  
Yuan Yang ◽  
Min Liu ◽  
Yuling Gan ◽  
Rong Liu ◽  
...  
2020 ◽  
Vol 15 ◽  
Author(s):  
Yuan Gu ◽  
Ying Gao ◽  
Xiaodan Tang ◽  
Huizhong Xia ◽  
Kunhe Shi

Background: Gastric cancer (GC) is one of the most common malignancies worldwide. However, the biomarkers for the prognosis and diagnosis of Gastric cancer were still need. Objective: The present study aimed to evaluate whether CPZ could be a potential biomarker for GC. Method: Kaplan-Meier plotter (http://kmplot.com/analysis/) was used to determine the correlation between CPZ expression and overall survival (OS) and disease-free survival (DFS) time in GC [9]. We analyzed CPZ expression in different types of cancer and the correlation of CPZ expression with the abundance of immune infiltrates, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells, via gene modules using TIMER Database. Results: The present study identified that CPZ was overexpressed in multiple types of human cancer, including Gastric cancer. We found that overexpression of CPZ correlates to the poor prognosis of patients with STAD. Furthermore, our analyses show that immune infiltration levels and diverse immune marker sets are correlated with levels of CPZ expression in STAD. Bioinformatics analysis revealed that CPZ was involved in regulating multiple pathways, including PI3K-Akt signaling pathway, cGMP-PKG signaling pathway, Rap1 signaling pathway, TGF-beta signaling pathway, regulation of cell adhesion, extracellular matrix organization, collagen fibril organization, collagen catabolic process. Conclusion: This study for the first time provides useful information to understand the potential roles of CPZ in tumor immunology and validate it to be a potential biomarker for GC.


2015 ◽  
Vol 11 (4) ◽  
pp. 370-379 ◽  
Author(s):  
Xiao-Jun Shen ◽  
Hao Zhang ◽  
Gu-Sheng Tang ◽  
Xu-Dong Wang ◽  
Rui Zheng ◽  
...  

2020 ◽  
Author(s):  
Qinghua Liu ◽  
Ying Zhang ◽  
Jiwei Zhang ◽  
Kun Tao ◽  
Brett D Hambly ◽  
...  

Abstract Background Gastric cancer (GC) is a malignancy with high morbidity/mortality, partly due to a lack of reliable biomarkers for early diagnosis. It is important to develop reliable biomarker(s) with specificity, sensitivity and convenience for early diagnosis. The role of tumour-associated macrophages (TAMs) and survival of GC patients are controversial. Macrophage colony stimulating factor (MCSF) regulates monocytes/macrophages. Elevated MCSF is correlated with invasion, metastasis and poor survival of tumour patients. IL-34, a ligand of the MCSF receptor, acts as a “twin” to MCSF, demonstrating overlapping and complimentary actions. IL-34 involvement in tumours is controversial, possibly due to the levels of MCSF receptors. While the IL34/MCSF/MCSFR axis is very important for regulating macrophage differentiation, the specific interplay between these cytokines, macrophages and tumour development is unclear.Methods A multi-factorial evaluation could provide more objective utility, particularly for either prediction and/or prognosis of gastric cancer. Precision medicine requires molecular diagnosis to determine the specifically mutant function of tumours, and is becoming popular in the treatment of malignancy. Therefore, elucidating specific molecular signalling pathways in specific cancers facilitates the success of a precision medicine approach. Gastric cancer tissue arrays were generated from stomach samples with TNM stage, invasion depth and the demography of these patients (n = 185). Using immunohistochemistry/histopathology, MCSF, IL-34 and macrophages were determined.Results We found that IL-34 may serve as a predictive biomarker, but not as an independent, prognostic factor in GC; MCSF inversely correlated with survival of GC in TNM III‑IV subtypes. Increased CD68+TAMs were a good prognostic factor in some cases and could be used as an independent prognostic factor in male T3 stage GC.Conclusion Our data support the potency of IL-34, MCSF, TAMs and the combination of IL34/TAMs as novel biological markers for GC, and may provide new insight for both diagnosis and cellular therapy of GC.


Author(s):  
Deli Mao ◽  
Rui Xu ◽  
Hengxing Chen ◽  
Xiancong Chen ◽  
Dongsheng Li ◽  
...  

Background: Focal adhesion, as the intermediary between tumor cells and extracellular matrix communication, plays a variety of roles in tumor invasion, migration, and drug resistance. However, the potential role of focal adhesion-related genes in the microenvironment, immune cell infiltration, and drug sensitivity of gastric cancer (GC) has not yet been revealed.Methods: The genetic and transcriptional perspectives of focal adhesion-related genes were systematically analyzed. From a genetic perspective, the focal adhesion index (FAI) was constructed based on 18 prognosis-related focus adhesion-related genes to evaluate the immune microenvironment and drug sensitivity. Then three prognosis-related genes were used for consistent clustering to identify GC subtypes. Finally, use FLT1, EGF, COL5A2, and M2 macrophages to develop risk signatures, and establish a nomogram together with clinicopathological characteristics.Results: Mutations in the focal adhesion-related gene affect the survival time and clinical characteristics of GC patients. FAI has been associated with a shorter survival time, immune signaling pathways, M2 macrophage infiltration, epithelial-mesenchymal transition (EMT) signaling, and diffuse type of GC. FAI recognizes ALK, cell cycle, and BMX signaling pathways inhibitors as sensitive agents for the treatment of GC. FLT1, EGF, and COL5A2 may distinguish GC subtypes. The established risk signature is of great significance to the prognostic evaluation of GC based on FLT1, EGF, and COL5A2 and M2 macrophage expression.Conclusion: The focal adhesion-related gene is a potential biomarker for the evaluation of the immune microenvironment and prognosis. This work emphasizes the potential impact of the focal adhesion pathway in GC therapy and highlights its guiding role in prognostic evaluation.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Zhaoji Pan ◽  
Yiqing Tian ◽  
Guoping Niu ◽  
Chengsong Cao

Mesenchymal stem cells (MSCs) have been declared to not only participate in wound repair but also affect tumor progression. Tumor-associated MSCs, directly existing in the tumor microenvironment, play a critical role in tumor initiation, progression, and development. And different tumor-derived MSCs have their own unique characteristics. In this review, we mainly describe and discuss recent advances in our understanding of the emerging role of gastric cancer-derived MSC-like cells (GC-MSCs) in regulating gastric cancer progression and development, as well as the bidirectional influence between GC-MSCs and immune cells of the tumor microenvironment. Moreover, we also discuss the potential biomarker and therapeutic role of GC-MSCs. It is anticipated that new and deep insights into the functionality of GC-MSCs and the underlying mechanisms will promote the novel and promising therapeutic strategies against gastric cancer.


2019 ◽  
Vol 2019 ◽  
pp. 1-15
Author(s):  
Mingfu Tong ◽  
Wenquan Lu ◽  
Hao Liu ◽  
Jian Wu ◽  
Mingzuo Jiang ◽  
...  

Background. Metallothioneins (MTs) family comprises many isoforms, most of which are frequently dysregulated in a wide range of cancers. However, the expression pattern and exact role of each distinct MT family isoform which contributes to tumorigenesis, progression, and drug resistance of gastric cancer (GC) are still unclear. Methods. Publicly available databases including Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, SurvExpress, MethHC, cBioportal, and GeneMANIA were accessed to perform an integrated bioinformatic analysis and try to detect fundamental relationships between each MT family member and GC. Results. Bioinformatic data indicated that the mRNA expression of all MT family members was almost lowly expressed in GC compared with normal gastric tissue (P<0.05), and patients with reduced mRNA expression of each individual MT member had inconsistent prognostic value (OS, FP, PPS), which depended on the individual isoform of MT. A negative correlation between the methylation in promoter region of majority of MT members and their mRNA expression was detected from MethHC database (p<0.001). Data downloaded from TCGA revealed that MTs were rarely mutated in GC patients and MT2A was frequently regulated by other three genes (FOS, JUN, SP1) in GC patients. Conclusion. MTs were nearly downregulated, and distinct type of MT harbored different prognostic role in GC patients. Methylation in gene promoter region of MTs partially contributed to their reduced expression in GC. Our comprehensive analyses from multiple independent databases may further lead researches to explore MT-targeting reagents or potential diagnostic and prognostic markers for GC patients.


2019 ◽  
Vol 244 (12) ◽  
pp. 953-959 ◽  
Author(s):  
Wei Deng ◽  
Yulong Zhang ◽  
Jun Cai ◽  
Jun Zhang ◽  
Xiaoye Liu ◽  
...  

Metastasis is the most challenging issue for gastric cancer, and identification of the molecular mechanism and suitable targets for treatment is the major purpose of recent research. In this study, we found the long non-coding RNA ANRIL was critical for the progression of gastric cancer. Knockdown of ANRIL (also known as CDKN2B-AS) with shRNA increased apoptosis, inhibited tumor growth, and suppressed migration of cancer cells. TET2 (Tet Methylcytosine Dioxygenase 2), a methylcytosine dioxygenase suppressed ANRIL function and prevented cancer progression. Patients with higher TET2 expression survived better, while with higher ANRIL survived worse. Furthermore, expressions of TET2 and ANRIL were negatively correlated in the patient samples. The mechanistic study suggested that ANRIL promoted tumor progression mainly by enhancing NF-kB signaling. Impact statement Gastric cancer is one of the leading causes of cancer-related death. The lack of curative therapeutic options ascribes to the complex genetic background and heterogeneity of gastric cancer. Understanding the molecular details of the disease and identifying the therapeutic targets would offer additional treatment options. Long non-coding RNA ANRIL was involved in the progression of many cancers, including gastric cancer, but the mechanism was unknown. The current study indicated that ANRIL supported tumor cell survival by inhibiting apoptosis and promoted metastasis by enhancing NF-kB signaling. NF-kB signaling was critical in tumor progression, and this study proved another long non-coding RNA that could regulate NF-kB signaling. ANRIL would be a potential biomarker and therapeutic target for gastric cancer prognosis and treatment.


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