Prognostic and predictive blood biomarkers in gastric cancer and the potential application of circulating tumor cells

Li, Tingting; Liu, Hao; Yu, Jiang; Shi, Guangyao; Zhao, Liying; Li, Guoxin

doi:10.3748/wjg.v24.i21.2236

Cited by 41 publications

(31 citation statements)

References 84 publications

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“…However, the mechanism underlying metastasis remains unclear. Recently, studies have demonstrated that metastasis is a multi‐step process that involves the presence of circulating tumor cells (CTCs) in the bloodstream and their growth in other organs . CTCs are singular cell or small cell masses that disseminate from primary tumors into blood vessels, and are usually identified by the following criteria: (a) atypical phenotype, with high nuclear to cytoplasm ratio or irregular shape; (b) intratumor heterogeneity, including the amplification of aneuploidy in chromosomes, altered cell‐surface antigen markers, molecular diversity, and varying mobility potential .…”

Section: Introductionmentioning

confidence: 99%

Epithelial‐mesenchymal transition may be involved in the immune evasion of circulating gastric tumor cells via downregulation of ULBP1

Tian

et al. 2020

Cancer Medicine

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Background:Increasing numbers of studies have demonstrated that circulating tumor cells (CTCs) undergo a phenotypic change termed epithelial-mesenchymal transition (EMT), and researchers have proposed that EMT might provide CTCs with increased potential to survive in the different microenvironments encountered during metastasis through various ways, such as by increasing cell survival and early colonization. However, the exact role of EMT in CTCs remains unclear. Methods: In this study, we identified CTCs of 41 patients with gastric cancer using Cyttel-CTC and im-FISH (immune-fluorescence in situ hybridization) methods, and tested the expression of EMT markers and ULBP1 (a major member of the NKG2Dnatural killer [NK] group 2 member D-ligand family) on CTCs. Moreover, we investigated the relationship between the expression of EMT markers and ULBP1 on CTCs and gastric cancer cell lines. Results: Our results showed that the CTCs of gastric cancer patients exhibited three EMT marker subtypes, and that the expression of ULBP1 was significantly lower on mesenchymal phenotypic CTCs (M + CTCs) than on epithelial phenotypic CTCs (E + CTCs). EMT induced by TGF-β in vitro produced a similar phenomenon, and we therefore proposed that EMT might be involved in the immune evasion of CTCs from NK cells by altering the expression of ULBP1. Conclusions: Our study indicated that EMT might play a vital role in the immune invasion of CTCs by regulating the expression of ULBP1 on CTCs. These findings could provide potential strategies for targeting the immune evasion capacity of CTCs.

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Section: Introductionmentioning

confidence: 99%

Epithelial‐mesenchymal transition may be involved in the immune evasion of circulating gastric tumor cells via downregulation of ULBP1

Tian

et al. 2020

Cancer Medicine

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“…CTCs are cells originating from solid tumors and are related to hematogenous dissemination [34]. Previous studies by our group suggested that CTCs are correlated with chemotherapy response [35,36]. In the present study, 43 patients were evaluated for CTCs, and 40 were CTC-positive.…”

Section: Discussionmentioning

confidence: 88%

Survival Analysis of Elderly Patients Over 65 Years Old With Stage Ii/iii Gastric Cancer Treated With Adjuvant Chemotherapy After Laparoscopic D2 Gastrectomy: a Retrospective Cohort Study

Liang

Zhao

Chen

et al. 2020

Preprint

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Background: The benefits of adjuvant chemotherapy for elderly patients (age >65) with gastric cancer (GC) remain unknown because elderly patients are underrepresented in most clinical trials. To evaluate the effectiveness and complications of adjuvant chemotherapy in elderly patients (>65 years of age) after laparoscopic D2 gastrectomy.Methods: This was a retrospective cohort study of elderly patients (>65 years) with stage II/III GC who underwent curative laparoscopic D2 gastrectomy between 2004 and 2018. The patients were divided as surgery alone and surgery plus adjuvant chemotherapy (chemo group). The overall survival (OS), disease-free survival (DFS), circulating tumor cells (CTCs), chemotherapy duration, and toxicity were examined. Results: There were 270 patients included: 169 and 101 in the surgery and chemo groups, respectively. There were ten (10/101) and six (6/101) patients with grade 3+ non-hematological and hematological adverse events. The 1-/3-/5-year OS rates of the surgery group were 72.9%/51.8%/48.3%, compared with 90.1%/66.4%/48.6% for the chemo group (log-rank test: P=0.018). For stage III patients, the 1-/3-/5-year OS rates of the surgery group were 83.7%/40.7%/28.7%, compared with 89.9%/61.2%/43.6% for the chemo group (log-rank test: P=0.015). Adjuvant chemotherapy was significantly associated with higher OS (HR=0.568, 95%CI: 0.357-0.903, P=0.017) and DFS (HR=0.511, 95%CI: 0.322-0.811, P=0.004) in stage III patients. CTC >0 had no significant impact on the benefits of adjuvant chemotherapy on OS and DFS.Conclusions: This study suggested that adjuvant chemotherapy significantly improves OS and DFS for elderly patients with stage III GC after D2 laparoscopic gastrectomy, with a tolerable adverse event profile.

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“…Biopsy is the best diagnostic method for early GC, but it is more traumatic for patients. Therefore, the diagnosis rate of early GC is low and there is no speci c tumor indicator [5][6][7]. It is on the urgent to nd speci c and sensitive diagnostic markers for gastric cancer.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Assessment of Plasma-Derived circ_0004771 as a Potential Biomarker in Tracking the Progression of Gastric Cancer

Kong

Qin

et al. 2020

Preprint

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Background: Due to the lack of specific and sensitive detection indicators, most patients with gastric cancer (GC) are already in the advanced stage at the time of diagnosis, resulting in a higher mortality. Therefore, it is urgent to search for effective diagnostic biomarkers with high specificity that can be applied in clinic. Methods: We screened out circ_0004771 through circRNA sequencing performed on three pairs of GC tissues and corresponding paracancerous tissues. Both exonuclease digestion assay, agarose gel electrophoresis (AGE) and sanger sequencing verified the potential of circ_0004771 being a biomarker. Additionally, we established quantitative real-time fluorescent Polymerase Chain Reaction (qRT-PCR) to detect the expression level of circ_0004771 and evaluated the methodology. What’s more, we collected plasma samples from GC patients, precancerous patients and gastritis patients, and we constructed the receiver operating characteristic curve (ROC) to appraise its diagnostic efficacy. Meanwhile, we collected the clinicopathological data of the patients to analyze the relationship between the expression level of circ_0004771 and the pathological parameters of the patients. Results: The expression level of circ_0004771 is up-regulated both in GC tissues and cells compared to normal controls. Circ_0004771 can be served as a promising biomarker because of its stable cyclic structure and longer half-life. The expression level of plasma circ_0004771 can distinguish between GC patients and precancerous patients, GC patients and gastritis patients. The diagnostic efficiency of circ_0004771 is higher than that of CEA and CA199. Higher diagnostic efficiency can be achieved in combination diagnosis. The expression level of plasma circ_0004771 in GC patients decreased after surgery, which can track the recovery condition of patients. Besides, the downstream regulatory forecast indicates that circ_0004771 may act as miRNA sponge to regulate the progression of GC.Conclusion: Plasma circ_0004771 can be served as a less invasive tumor biomarker with high diagnostic values.

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Prognostic and predictive blood biomarkers in gastric cancer and the potential application of circulating tumor cells

Cited by 41 publications

References 84 publications

Epithelial‐mesenchymal transition may be involved in the immune evasion of circulating gastric tumor cells via downregulation of ULBP1

Epithelial‐mesenchymal transition may be involved in the immune evasion of circulating gastric tumor cells via downregulation of ULBP1

Survival Analysis of Elderly Patients Over 65 Years Old With Stage Ii/iii Gastric Cancer Treated With Adjuvant Chemotherapy After Laparoscopic D2 Gastrectomy: a Retrospective Cohort Study

Comprehensive Assessment of Plasma-Derived circ_0004771 as a Potential Biomarker in Tracking the Progression of Gastric Cancer

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