Impact of intratumoural CD73 expression on prognosis and therapeutic response in patients with gastric cancer

2021 ◽  
Vol 157 ◽  
pp. 114-123
Author(s):  
Xudong He ◽  
Yun Gu ◽  
Yifan Cao ◽  
Baoying Hu ◽  
Hanji Fang ◽  
...  
Author(s):  
Shilang Xiao ◽  
Xiaoming Liu ◽  
Lingzhi Yuan ◽  
Fen Wang

Background: Accumulating literature demonstrates that long noncoding RNAs (lncRNAs) are involved in ferroptosis and gastric cancer progression. However, the predictive value of ferroptosis-related lncRNAs for prognosis and therapeutic response is yet to be elucidated in gastric cancer (GC).Method: The transcriptomic data and corresponding clinical information of GC patients were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. The association between ferroptosis-related lncRNAs and ferroptosis regulators was analyzed by Spearman correlation analysis. Then, we established a risk predictive model based on the ferroptosis-related lncRNAs using multivariate Cox regression analysis. Furthermore, we performed correlation analysis for the risk score and characteristics of biological processes, immune landscape, stromal activity, genomic integrity, drug response, and immunotherapy efficacy.Results: We constructed a 17-ferroptosis-related-lncRNA signature via multivariate Cox analysis to divide patients into two groups: low- and high-risk groups. The low-risk group was linked to prolonged overall survival and relapse-free survival. The risk score had good predictive ability to predict the prognosis of GC patients compared with other clinical biomarkers. We found that the high-risk group was associated with activation of carcinogenetic signaling pathways, including stromal activation, epithelial-mesenchymal-transition (EMT) activation, and immune escape through integrated bioinformatics analysis. In contrast, the low-risk group was associated with DNA replication, immune-flamed state, and genomic instability. Additionally, through Spearman correlation analysis, we found that patients in the high-risk group may respond well to drugs targeting cytoskeleton, WNT signaling, and PI3K/mTOR signaling, and drugs targeting chromatin histone acetylation, cell cycle, and apoptosis regulation could bring more benefits for the low-risk group. The high-risk group was associated with poor immunotherapy efficacy.Conclusion: Our study systematically evaluated the role of ferroptosis-related lncRNAs in t tumor microenvironment, therapeutic response, and prognosis of GC. Risk score–based stratification could reflect the characteristic of biological processes, immune landscape, stromal activity, genomic stability, and pharmaceutical profile in GC patients. The ferroptosis-related lncRNA signature could serve as a reliable biomarker to predict prognosis and therapeutic response of patients with GC.


2021 ◽  
pp. 172460082098197
Author(s):  
Yinxing Zhu ◽  
Nan Chen ◽  
Manman Chen ◽  
Xiaowen Cui ◽  
Han Yang ◽  
...  

Background: Circulating tumor cells and serum tumor markers have been found significant in predicting outcome for several malignancies. However, their role in gastric cancer is not fully clarified. We conducted a retrospective study to explore the prognostic value of circulating tumor cells and their applicability in assessing the treatment efficacy in gastric cancers. Methods: From September 2015 to December 2018, 116 patients with newly pathologically diagnosed gastric adenocarcinoma were enrolled. At both baseline and two courses after chemotherapy, the data of circulating tumor cells and serum tumor markers, such as CEA, CA72-4, CA19-9, CA50, and CA242, were collected. The relationships between the change trend of circulating tumor cells and the treatment efficacy were analyzed after chemotherapy, with a paired t-test. Univariate and multivariable analysis were used to find prognostic factors for overall survival (OS). Results: We found there is a significant difference between the circulating tumor cells-positive and circulating tumor cells-negative before and after therapy (mOS 12.6 vs. 31.6 months, P<0.001; mOS 12.4 vs. 24.2 months, P=0.002), respectively. Also, differentiation, pre-therapeutic circulating tumor cells and therapeutic response were independent predictors of overall survival. Following two courses of chemotherapy, the number of circulating tumor cells increased obviously in the progressive disease group ( P=0.002), while they decreased in the non-progressive disease group ( P=0.02). Thus, the change in the circulating tumor cells count had a close association with the therapeutic response ( P=0.004). Conclusion: Generally, circulating tumor cells provide a novel tool to evaluate the outcomes of gastric cancer patients. Since the change of circulating tumor cells was highly related to treatment response, it may be an auxiliary to assess the effect of chemotherapy, leading an earlier adjustment of following regimens.


2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Zuhua Chen ◽  
Cheng Zhang ◽  
Mengqi Zhang ◽  
Beifang Li ◽  
Yunyun Niu ◽  
...  

Abstract Gastric cancer is characterized by chromosomal instability. In this study, we investigated chromosomal instability quantified by copy number instability (CNI) score of circulating tumor DNA (ctDNA) during the drug treatment in advanced gastric cancer (AGC). A total of 55 pretherapeutic plasmas from 55 AGC patients and 75 plasmas during drug treatment of 26 AGC patients were collected. Plasma ctDNA was extracted and assessed by whole-genome sequencing (WGS) for somatic copy number alteration (SCNA), and according to which we calculated the CNI scores. We next assessed the correlations between chromosomal instability and therapeutic response. The cutoff value of chromosomal instability was defined as the mean + SD of the CNI scores (56.60) in cfDNA of plasmas from 100 healthy people. For 55 enrolled cases, chromosomal instability was observed in 27 (49%) prior to drug treatment, whose response rate (59%, 16/27) was higher than in 28 patients with stable chromosomes (32%, 9/28, P = 0.043). We also observed that CNI scores fluctuated during treatment in 26 patients. Specifically, the CNI scores in 93% (14/15) of patients sensitive to drug treatment reduced to the level of chromosomal stability and the CNI scores in 52% (13/25) of patients resistant to treatment elevated again. For ctDNA with developed resistance, the SCNA patterns were identical to those before treatment, whereas the CNI scores were lower than the pretherapeutic scores. We found that chromosomal instability based on ctDNA could predict and monitor therapeutic response in gastric cancer, although validation in a larger cohort will be necessary.


Author(s):  
Dong Yuming ◽  
Yang Guanglin ◽  
Du Wei Dong ◽  
Xu Ai Liam

The activities and distributions of AKPase ,ACPase,G6Pase,TPPase and COase in human normal gastric mucosa and gastric cancer tissues were studied histochemically at light microscopic level. These enzymes are the marker enzymes of cell membrane lysosome endoplasmic reticulum, Golgi apparatus and mitochondrion objectively. On the basis of the research we set up a special ultrastructural cytochemical technique and first researched into gastric cancer domesticly. Ultrastructural cytochemistry is also called electron microscopic cytochemistry. This new technique possesses both the sensitivity of cytochemical reaction andi the high resolution of electron microscope. It is characterized by direct observation,exact localization and the combination morphology with function.The distributions of AKPase,ACPase,G6Pase,TPPase and COase in 14 cases of gastric cancer and 1 case of gastric Denign lesion were studied ultrastructurally. The results showed: 1. normal gastric epithelium had no AKPase reaction. The reaction of ACPase,G6Pase,TPPase and Coase were found in the corresponding organella, which were consistent with their function.


Author(s):  
Dong Yuming ◽  
Yang Guanglin ◽  
Wu Jifeng ◽  
Chen Xiaolin

On the basis of light microscopic observation, the ultrastructural localization of CEA in gastric cancer was studied by immunoelectron microscopic technique. The distribution of CEA in gastric cancer and its biological significance and the mechanism of abnormal distribution of CEA were further discussed.Among 104 surgically resected specimens of gastric cancer with PAP method at light microscopic level, the incidence of CEA(+) was 85.58%. All of mucinous carcinoma exhibited CEA(+). In tubular adenocarcinoma the incidence of CEA(+) showed a tendency to rising with the increase of degree of differentiation. In normal epithelia and intestinal metaplasia CEA was faintly present and was found only in the luminal surface. The CEA staining patterns in cancer cells were of three types--- cytoplasmic, membranous and weak reactive type. The ultrastructural localization of CEA in 14 cases of gastric cancer was studied by immunoelectron microscopic technique.There was a little or no CEA in the microvilli of normal epithelia. In intestinal metaplasia CEA was found on the microvilli of absorptive cells and among the mucus particles of goblet cells. In gastric cancer CEA was also distributed on the lateral and basal surface or even over the entire surface of cancer cells and lost their polarity completely. Many studies had proved that the alterations in surface glycoprotein were characteristic changes of tumor cells. The antigenic determinant of CEA was glycoprotein, so the alterations of tumor-associated surface glycoprotein opened up a new way for the diagnosis of tumors.


2010 ◽  
Vol 34 (8) ◽  
pp. S54-S54
Author(s):  
Dong Xu ◽  
Ying Chang ◽  
Huiying He ◽  
Yingyu Chen

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