Fangxuan Li

The correlation between pre-operative serum tumor markers and lymph node metastasis in gastric cancer patients undergoing curative treatment

Abstract Background: There was few study concentrated on the correlation between the evaluated tumor markers and lymph node metastasis. In this study, we aimed to evaluate the correlation between the CA724, CA242, CA199, CEA and the lymph node metastasis of gastric cancer and assess the prognostic value of them in different N stage patients. Methods: We analyzed the correlation between serum level of CA724, CA242, CA199, CEA and lymph node metastasis in 1501 gastric cancer patients. Results: Lymph node metastasis of gastric cancer was related with tumor location, Bormann type, tumor size, histological type, depth of invasion and TNM stage (p < 0.05). The values of CA724, CA242, CA199 and CEA were positively correlated with the metastatic lymph node counts and the N stage (p < 0.05). The later the N stage was, the levels of CA724, CA242 and CA199 were higher. The later the N stage was, the positive rates of tumor markers were higher (p < 0.05). In comparing with single tumor markers, the positive rates of tumor markers combination were higher. The combination of CA724 + CA242 + CA199 + CEA had highest positive rate. The higher CEA level related to N1 stage patients while higher CA199 was related with poor prognosis for N1 stage patients. For N0 and N2 stage patients, evaluation of CA724 indicated poorer prognosis. For N1 and N2 stage gastric patients, the patients with increased CA242 inclined to have shorter survival time. Conclusions: The tumor makers CA724, CA242, CA199 and CEA were evaluated significantly in the gastric patients with later N stage. The combination of these four tumor markers maybe prefer diagnostic index of gastric cancer and its lymph node metastasis. These tumor markers can be a possible indicator of poorer prognosis in different N stage patients.

Significance of Thrombocytosis in Clinicopathologic Characteristics and Prognosis of Gastric Cancer

PURPOSE We aimed to study the relationship between thrombocytosis and clinical features of gastric cancer focussing on platelet counts and gastric cancer progression through different TNM stages. METHODS According to the normal range of platelet count in our institution, 1,596 patients were divided to two groups: a thrombocytosis group (120 patients, >400?1000/μL) and a control group (1,476 patients, ≤400?1000/μL). RESULTS The incidence of thrombocytosis was 7.5%. Higher platelet counts were observed in patients with older age, larger tumor size, deeper invasion, lymph node metastasis, distant metastasis and advanced TNM stage. In multivariate logistic regression, tumor size, depth of tumor invasion, lymph node metastasis and TNM stage were independent risk factors for thrombocytosis of gastric cancer patients. On prognostic analysis, age, tumor size, tumor location, histologic type, depth of tumor invasion, lymph node metastasis, distant metastasis and TNM stage and platelet count were important factors. Tumor size, invasion depth, lymph node metastasis, TNM stage and the platelet count were independent prognostic factors. CONCLUSION Thrombocytosis is associated with clinical features of gastric cancer patients and correlates with a poor prognosis.

IDO1: An important immunotherapy target in cancer treatment

Abstract Indoleamine 2,3‐dioxigenase 1 (IDO1) acts in pathogenic inflammatory processes and engender immune tolerance to tumor antigens. IDO1 can decrease the tryptophan and produce a series of toxic kynurenine metabolites to promote the immune toleration via GCN2 pathway, mTOR pathway, toxic effect of kynurenine and favoring differentiation of Tregs. IDO1 can be induced in most human cells, especially APCs and cancer cells through canonical and non‐canonical NF‐&kgr;B and Jak/STAT pathways, as well as PKC and TGF‐&bgr; signaling pathways. A series of human cancers over‐express IDO1 in a constitutive way. Thus, IDO1 is likely to be an attractive target for developing inhibitors of tumor treatments. Many preclinical and clinical trials have been underway and suggest that IDO1 inhibitor maybe an effective tool against a wide range of cancers. However, the IDO1 inhibitor alone had been verified that to be disappointment in achieving effective antitumor efficacy. Concentrating on its molecular mechanism in immune toleration and complex environments of cancer, IDO1 inhibitor could cooperate with chemotherapies and other immune target inhibitors to lessen the tumor. HighlightConcentrating on molecular mechanism of IDO1 in immune toleration and complex environments of cancer, IDO1 inhibitor could cooperate with chemotherapies and other immune targets to lessen the tumor as possible.

The effect of antisense inhibitor of miRNA 106b∼25 on the proliferation, invasion, migration, and apoptosis of gastric cancer cell

Accumulating data has demonstrated that miRNA 106b∼25, which are composed of the highly conserved miRNA 106b, miRNA 93, and miRNA 25, play carcinogenic roles in cancers. We investigated the expression of miRNA 106b∼25 in gastric cancer cells (SGC 7901, MGC 803, BGC 823) and normal gastric epithelial cell then inhibited miRNA 106b∼25 expression via transiently transfecting their antisense inhibitor. After miRNA 106b∼25 cluster was inhibited, MTT, Scratch test, Transwell invasion test, and flow cytometry were applied to investigate the proliferation, invasion, migration, cell cycle, and apoptosis of gastric cancer cell. The expression of miRNA 106b, miRNA 93, and miRNA 25 in gastric cancer cells SGC 7901, MGC 803, and BGC 823 was significantly higher than in gastric epithelial cell GES-1. The most significant suppression of miRNA 106b∼25 expressions can be detected in MGC 803 cell after transiently transfecting their antisense inhibitors. So, MGC 803 cell was selected as our research object. After inhibiting miRNA 106b and miRNA 93 respectively and combined, the proliferation, migration, and invasion of gastric cancer cell MGC 803 were significantly suppressed. The most significant suppression was observed in combined inhibiting group. After miRNA 106b∼25 cluster was inhibited respectively or combined, more gastric cancer cells were arrested in the G0G1 phase. However, there was no statistical difference in comparing with control groups. While the percentages of apoptotic cells increased after miRNA 106b∼25 cluster was inhibited, the statistical difference was detected only in combined inhibiting group. Inhibiting miRNA 106b∼25 cluster via transfecting antisense inhibitor can influence biological behavior of gastric cancer cell.

Role of microRNA-93 in regulation of angiogenesis

Angiogenesis is essential for a wide variety of physiological and pathological processes. To date, many angiogenic microRNAs (miRNAs) have been identified and several of them were further investigated to elucidate the mechanisms of specific miRNAs in regulating angiogenesis. In recent studies concerning tumor and ischemia, the miRNA-93 had been demonstrated to be able to modulate angiogenesis in different molecular pathways. The miRNA-93 can promote angiogenesis via enhancing endothelial cell proliferation, migration, and tube formation. Additionally, miRNA-93-over-expressing cells developed a relationship with the blood vessels allowing tumor cells to survive and to grow well. However, high expression of miRNA-93 can depress the vascular endothelial growth factor (VEGF) secretion and its downstream molecular targets in in vivo and vitro experiments. MiRNA-93’s effects on angiogenesis are dependent on the interaction of other multiple genes and signal pathways, such as P21, E2F1, integrin-β8, LATS2, etc. Future investigation should involve mapping the network by which miRNA-93 exerts its functions.

The clinical significance of memory T cells and its subsets in gastric cancer

BackgroundLong life of memory T cell (Tm) determines its crucial role in the carcinogenesis and carcinogenic progression which usually take long time. The Tm compartment contains two populations, central memory T cells (Tcm) and effector memory T cells (Tem), based on their phenotypic markers, functional attributes, and migratory properties.MethodsWe investigated the subsets of the Tm in peripheral blood and tumor microenvironments in patients with gastric cancer by flow cytometry, and aimed to explore the correlation between the Tm and clinicopathologic features of gastric cancer.ResultsThe percentages of CD4+/CD8+ Tm and CD4+/CD8+ Tcm in peripheral blood from gastric cancer patients were statistically lower, whereas the percentages of CD4+/CD8+ Tem were significantly higher than healthy controls. The proportion of CD4+/CD8+ Tcm increased after tumor resection, while the percentage of the CD4+/CD8+ Tem decreased significantly. Significant associations were detected between the peripheral CD4+/CD8+ Tm and clinical stage, as well as the CD8+ Tcm and clinical stage and nodal involvement. Tumor infiltrating CD8+ Tm expressed both central and effector memory phenotypes, whereas CD4+ Tm displayed predominantly an effector memory phenotype. Higher percentages of tumor infiltrating CD4+/CD8+ Tm were significantly associated with the early disease stage.ConclusionsTm and its subsets were good immune indicators for the disease stage of gastric cancer. The proportion of Tm subsets may reflect the immune suppressive and immune response to the tumor associated antigen.

The subsets of dendritic cells and memory T cells correspond to indoleamine 2,3-dioxygenase in stomach tumor microenvironment

The abnormal distributions of memory T cells (Tm) and dendritic cells (DC) in stomach cancer are not well understood. Indoleamine 2,3-dioxygenase (IDO), produced by DC, may be an important enzyme affecting function and proliferation of Tm. In this study, IDO expression was examined by immunohistochemical staining. The subsets of Tm and DC were counted by flow cytometry. The percentages of CD4 + Tm and CD4 + central Tm (Tcm) were lower in tumor tissues than in normal tissues (P < 0.05), while the CD4 + effector Tm (Tem) and CD8 + Tem percentages were higher in tumor tissues (P < 0.05). The ratio of myeloid DC (DC1)/plasmacytoid DC (DC2) was significantly lower in tumor tissues (P = 0.009). The high expression of IDO was more frequently observed in tumor tissues (P = 0.001). The percentages of CD4 + Tm and CD8 + Tm were positively associated with DC1 percentage and ratio of DC1/DC2 (P < 0.05). The higher CD8 + Tcm percentage was associated with higher DC2 percentage (P = 0.025). The patients with high IDO expression had significantly lower CD4 + Tm (P = 0.012) and CD8 + Tm percentages (P = 0.033), but higher CD8 + Tem percentage (P < 0.01). Concerning on clinicopathologic features, the higher DC2 percentage was associated with larger tumor size (P = 0.019). The CD4 + Tm and CD8 + Tem percentages were significantly associated with clinical stage and lymph node metastasis; the high IDO expressions were significantly associated with deeper tumor invasion (P = 0.016) and lymph node metastasis (P = 0.038). Thus, DC subsets, Tm subsets, and IDO expression were correlated with each other. They were associated with the established clinicopathologic features, such as tumor size, depth of invasion, lymph node metastasis, and clinical stage.

High Indoleamine 2,3-Dioxygenase Is Correlated With Microvessel Density and Worse Prognosis in Breast Cancer

Indoleamine 2,3-dioxygenase (IDO), which catalyzes the breakdown of the essential amino acid tryptophan into kynurenine, is understood to have a key role in cancer immunotherapy. IDO has also received more attention because of its non-immune functions including regulating angiogenesis. The purpose of this study was to investigate the effects of IDO on microvessel density (MVD), and to explore its prognostic role in breast cancer. We showed IDO expression was positively correlated with MVD labeled by CD105 (MVD-CD105) rather than MVD labeled by CD31 (MVD-CD31) in breast cancer specimens. Both IDO expression and MVD-CD105 level were associated with initial TNM stage, histological grade, and tumor-draining lymph nodes (TDLNs) metastasis in breast cancer. In the prognostic analysis, TDLNs metastasis, an advanced TNM stage (III) and high histological grade (III) significantly predicted shorter survival in univariate analysis. Concentrating on IDO and MVD, the patients with IDO expression or high MVD level had poorer prognosis compared with no IDO expression [P = 0.047 for progress-free survival (PFS)] and low MVD level (P = 0.019 for OS); the patients with IDO expression and high MVD level had a tendency with shorter overall survival when compared with non IDO expression, low MVD level, or both (P = 0.062 for OS). In multivariate analysis, an advanced TNM stage (III) was significantly associated with shorter 5-year survival rate of PFS (HR: 0.126, 95% CI: 0.024–0.669, P = 0.015). In order to verify the phenomenon of IDO promoting angiogenesis, we contained the study in vitro. We detected the expression of IDO mRNA in breast cancer cell lines and measured the concentration of tryptophan and kynurenine in the supernatants of MCF-7 by high performance liquid chromatography. The ratio of Kyn and trp (kyn/trp) was calculated to estimate IDO-enzyme activity. MCF-7 cells, which produce high level of IDO and metabolize tryptophan, promoted human umbilical vein endothelial cells (HUVEC) proliferation significantly in co-culture system. Meanwhile IDO could upregulate the expression of CD105 in HUVEC, which was downregulated after adding IDO inhibitor, 1-methyl-d-trytophan. These results suggest that IDO could promote angiogenesis in breast cancer, providing a novel, potentially effective molecular or gene therapy target for angiogenesis inhibition in the future.

The Association Between Metabolic Syndrome and Gastric Cancer in Chinese

Background: Metabolic syndrome (MetS) play a carcinogenic role in variety of cancers and influence the prognosis of cancer patients both systemically and hormonally. Methods: The data of clinicopathologic features and MetS of 808 gastric cancer patients and 1,146 randomly healthy controls were analyzed retrospectively. Results: Higher TG level, lower HDL-C level and higher hypertension frequency were observed in all gastric cancer patients when compared with healthy controls. While, gastric cancer patients had greater waist circumference only in females. Among three definitions of MetS, the MetS identified by the Chinese Diabetes Society (CDS) was associated with the most significant increasing risk of gastric cancer. Comparing all gastric cancer patients with healthy controls, OR of gastric cancer was enhanced by various individual components of the MetS, including higher TG level, lower HDL-C level, hypertension and diabetes; In male subgroup, OR of gastric cancer was enhanced by higher BMI, hypertension and diabetes; In females, OR of gastric cancer was enhanced by lower HDL-C, hypertension and diabetes. MetS was associated with poor differentiated carcinoma, more advanced pathological T, N stage and TNM stage of gastric cancer. Conclusion: The presence of MetS and its components were increased in gastric cancer, especially in gastric cancer patients with poor differentiation and advanced stage, which implies that metabolic disorder may play an important role in the development of gastric cancer.