The roles of serum PDCD5 in circulating CD133 positive cells of the patients with gastric cancer.

Cancer stem cells are responsible for the development, metastasis, recurrence, and drug resistance of cancer. More and more studies exhibited that the circulating CD133+ cells is a marker for the prognosis of various malignancies. Programmed cell death protein 5 (PDCD5) can promote apoptosis in different tumor cell types in response to various stimuli. However, the impact of PDCD5 on circulating CD133+ cells of gastric cancer patients remains unclear. In this study, we detected serum PDCD5 level in blood samples of the patients with gastric cancer by using ELISA. MTT assay, sphere assay, and wound healing assay were used to test the anti-tumor effects of rhPDCD5 on CD133+ cells in vitro. Lower serum levels of PDCD5 protein were identified in the gastric cancer patients that with CD133+ fraction more than 1.6 %. No difference between healthy controls and the gastric cancer patients that with CD133+ fraction less than 1.6 %. Serum PDCD5 was correlated with the favorable prognosis of patients with gastric cancer. In the last, we confirmed that rhPDCD5 could induce apoptosis, and inhibit the proliferation, colony formation, and mobility of CD133+ cells in vitro by suppressing MEK/ERK pathway. Serum PDCD5 could be considered as a potential drug for the gastric cancer patients with circulating CD133+ cells.

The role of beclin-1 expression in patients with gastric cancer: a meta-analysis.

Beclin-1 has been identified as a reliable biomarker in monitoring the prognosis for tumors. We carried out a meta-analysis focusing on the relationship between beclin-1 and the clinical characteristics of patients with gastric cancer. We identified articles in MEDLINE, PubMed, Embase, ISI Web of Science, and Chinese National Knowledge Infrastructure databases by using the following strategy: ("beclin 1" or "beclin-1" or "ATG6") and ("gastric cancer" or "stomach cancer"). We conducted a final analysis of 1,254 patients from seven studies. The pooled odds ratio (OR) indicated a significant association between beclin-1 expression and the differentiation of gastric cancer (pooled OR = 0.23; 95 % confidence interval (CI) = 0.07-0.73) or tumor-node-metastasis staging of gastric cancer (pooled OR = 0.62; 95 % CI = 0.48-0.79). Beclin-1 expression was different in intestinal- and diffuse-type gastric cancer (pooled OR = 0.55; 95 % CI = 0.39-0.77). No association between beclin-1 and tumor size (pooled OR = 0.73; 95 % CI = 0.45-1.17) or lymph node metastasis (pooled OR = 0.59; 95 % CI = 0.17-1.99) was observed.

Different races have different immune microenvironments: comparison of White and Asian patients with liver cancer.

Different ethnic groups have different incidence rate of hepatocellular carcinoma (HCC). In addition to lifestyle and environmental factors, genetic susceptibility is also an important reason. In this study, we screened the immune related genes and stromal related genes in White and Asian liver cancer patients cohort of The Cancer Genome Atlas (TCGA) the using ESTIMATE algorithm. Hub genes that significantly associated with overall survival (OS) were selected from White and Asian liver cancer patients, respectively. In addition, we validated the functions of two hub genes, IL-18RAP and GPM6A, in vivo and in vitro. We confirmed different races have different tumor immune microenvironments. Immune microenvironment can influence and change the efficacy of immunotherapy for liver cancer patients.

Effect of secretory DKK3 on circulating CD56bright natural killer cells in patients with liver cancer.

BACKGROUND: Liver cancer seriously threatens human health. Natural killer (NK) cells are an important part of the innate immune system and have strong anti-tumor ability. Immunotherapy based on NK cells has become a hot topic in the treatment of liver cancer. METHODS: In this study, we checked the serum DKK3 (sDKK3) and circulating CD56bright NK cells using ELISA and flow cytometry, respectively, in the blood of liver cancer patients. The effect on recombinant human DKK3 (rhDKK3) on CD56bright NK cells was analyzed in vitro. RESULTS: We found low levels of sDKK3 in liver cancer patients and a negative correlation between sDKK3 and circulating CD56bright NK cells. In addition, we found that DKK3 induced the differentiation and improved the cytotoxicity of CD56bright NK cells for the first time. It could be used as an agonist for NK cell-based immunotherapy. CONCLUSIONS: Improving the clinical efficacy of NK cells through DKK3 will become a new strategy for cancer immunotherapy.

The role of the stemness index-associated signature in the analysis of the tumorigenesis of liver cancer patients of different races.

Cancer stem cells (CSCs) are a subset of cancer cells with stem cell characteristics. The discovery of CSCs has opened a new era for cancer research. CSCs not only play a critical role in tumorigenesis, but also are responsible for the failure of cancer treatments. Here, we performed weighted gene co-expression network analysis (WGCNA) to identify key stemness genes and prognostic signatures using the data of an Asian liver cancer patient cohort and a White liver cancer patient cohort in The Cancer Genome Atlas (TCGA) database. To compare the difference in tumorigenesis between the Asian patients and the White patients, the prognostic value of the key genes from the Asian patients was evaluated in the White patient cohort and vice versa. We found that some key genes could predict the survival of the patients regardless of race. In addition, the key genes, NUCB2 and KLF4A, were selected from Asian patients and White patients, respectively, for further experimental validation. Knocking down NUCB2 could inhibit the activity of the AKT/mTOR signaling pathway and reverse the epithelial-mesenchymal transition (EMT) in liver cancer cells. We also confirmed that the knockdown of KLF4A suppressed ABCG2 activity and reduced the side population (SP) in liver cancer cells for the first time. Our results suggest that the stemness index is a useful method to identify key genes in tumorigenesis. Compared to the analysis for all patients, applying this index to the analysis of the patients of different races will provide more potential therapeutic targets for cancer treatment.

[Prognostic analysis of clinicopathological factors in patients after radical resection of esophageal carcinoma].

OBJECTIVE: To explore factors affecting the survival in patients after radical resection of esophageal carcinoma, and to provide a valuable reference for selecting treatment protocol after surgery. METHODS: Clinicopathological data of 618 esophageal cancer patients who underwent radical resection at the Fourth Hospital of Hebei Medical University from May 2002 to June 2006 were collected and reviewed in this study. All patients had no cancer history, did not receive preoperative radiotherapy or chemotherapy, and had Karnofsky performance scores ≥ 70. Univariate analysis was performed by using log-rank test to determine predictors of survival, and multivariable analysis was performed by a Cox regression model. RESULTS: The overall 1-, 3-, 5-year survival rates were 83.32%, 53.33%, 36.02%, respectively, and the median survival time was 38.33 months. The Cox regression analysis showed that operation mode, intraoperative findings of the extent of tumor invasion, pathological T stage, and the number of metastatic lymph nodes were significant predictors of survival. For patients with lymph node metastasis, the overall 1-, 3-, and 5-year survival rates did not significantly differ between the operation alone group and the postoperative prophylactic radiotherapy group. For patients without lymph node metastasis, the 1-, 3-, and 5-year survival rates were 94.34%, 51.55%, and 34.41%, respectively, in the postoperative radiotherapy group, significantly higher than those in the operation alone group (63.08%, 23.30% and 4.36%; χ(2) = 15.99, P < 0.01). CONCLUSIONS: The independent prognostic factors of esophageal cancer patients after radical resection include the operation mode, intra-operative findings of the extent of tumor invasion, pathological T stage, the number of lymph node metastasis and the number of regions of lymph node metastasis. Postoperative prophylactic radiotherapy is beneficial for esophageal cancer patients with lymph node metastasis.

Amino acid profiles in the tissue and serum of patients with liver cancer.

Most patients with liver cancer were found late and lost the chance of surgery. Liquid biopsy can monitor the risk of tumor recurrence and metastasis, quickly evaluate the curative effect of tumor treatment, and is conducive to early screening and auxiliary diagnosis of high-risk groups. Amino acid (AA) profiling has been used to the diagnosis and the prognosis for cancers. However, little was known about the profiles of AA of liver cancer. In this study, we used tRNA in Cancer database to analyze the AA levels in liver cancer tissues. Blood samples of patients with liver cancer were collected and analyzed using the automatic AA analyzer. We found that valine, isoleucine, and leucine were decreased significantly both in the plasma and the tumor tissues of patients with liver cancer. However, upregulation of methionine was observed in tissues and plasma of patients with liver cancer. Interestingly, tyrosine, and phenylalanine were decreased in tumor tissue but increased in the plasma of patients with liver cancer. This is the first report provided an overview of AA profile in both plasma and tissue for patients with liver cancer. AA levels can be used as diagnostic and prognostic markers of patients with liver cancer.

[Exploration of the classification of gross tumor volume and pathological staging of esophageal carcinoma].

OBJECTIVE: Using the volume calculating function of treatment planning system of 3DCRT to work out the value of GTV standard classifications and to provide the reference for clinical staging of esophageal carcinoma. METHODS: Six hundred and seven patients underwent radical resection of thoracic esophageal carcinoma in our hospital, and their pre-operative CT images were transmitted in digital format to the three-dimensional conformal radiotherapy planning system by the network. Esophageal lesion GTV targets were outlined, and their volumes were automatically computed by the planning system. Compared the differences of the GTV volumes in different pathological T stages, and analyzed the relationship between GTV volumes and pathological T stages. According to the median volume of GTV at different pathological T stages, divided the values of GTV volume corresponding to different T stages and selected the suitable classification standard of GTV volume. RESULTS: The esophageal carcinoma GTV length, maximum diameter and volume were related to pathological T staging and with a positive correlation (all P < 0.001). The Spearman correlation coefficient (r) was 0.376, 0.466 and 0.464, respectively, P < 0.001. Except that the length, maximum diameter and volume of GTV in pathological T3 and T4 had no significant difference, other indicators of the pathological T stages showed significant differences between the groups (P < 0.001). According to the median volume of GTV at different pathological T stages, the GTV volumes were divided into three grades: 13.0 cm(3). When compared them with pathological T1, T2, and T3-T4 stages, the coincidence rate was 73.8%. The consistency was good between the GTV volume grades and pathological T stages (Kappa = 0.40, P < 0.001). The overall 5-year survival rates of GTV grades 1, 2, 3 were 78.1%, 31.5% and 33.5%, respectively (P < 0.0001). If the GTVs were divided into four grades: 39.0 cm(3), the coincidence rate of GTV volume grades and pathology T staging was only 54.7%, and the consistency was poor, Kappa = 0.24, P < 0.001. The overall 5-year survival rate of GTV 1, 2, 3, 4 were 78.1%, 31.5%, 36.2% and 27.5%, respectively (P < 0.0001). CONCLUSION: The length, maximum diameter and volume of esophageal carcinoma GTV are related to pathological T staging with a positive correlation. The classification that esophageal carcinoma GTVs divided into three grades has a good coincidence with the pathological T staging.

[Characteristics of the lymph node metastases and influencing factors and their value in target region delineation in postoperative radiotherapy for thoracic esophageal carcinoma].

OBJECTIVE: To explore the distribution of lymph node metastases, to analyze the cliniopathologic factors of thoracic esophageal carcinoma after curative resection, and to provide the criteria of irradiated region delineation in radiotherapy for esophageal carcinoma. METHODS: The clinicopathological data of 763 patients who underwent esophagecotomy from Jun 2002 to Jun 2006 were retrospectively analyzed. The regularity of lymph node metastases of thoracic esophageal cancer and clinicopathological factors were stratified and analyzed with SPSS13.0 software. RESULTS: Of the 763 patients, a total of 5846 lymph nodes were dissected with an average of 7.7 lymph nodes in each case. Metastatic lymph nodes were 711, the ratio of metastatic lymph node was 12.2%, and 297 patients had lymph node involved, the lymph node metastasis rate was 38.9%. The metastatic lymph nodes of upper-thoracic esophagus were mainly observed in the supraclavicular and paratracheal regions (P < 0.05), the metastatic lymph nodes of middle-third thoracic esophagus were bidirectional, and those of the lower-third thoracic esophagus mainly metastasized to the regions adjacent to the esophagus, gastric cardia and gastric artery (P < 0.05). Both the metastasis ratio and rate of lymph nodes adjacent to the gastric artery in the lower-thoracic esophageal cancer were significantly higher than those in the middle-third and upper-third thoracic esophageal cancers (P = 0.007, P = 0.001). The multiple factors logistic regression analysis showed that tumor length, depth of tumor invasion, vascular tumor emboli and distant metastasis were major factors for lymphatic metastasis (P < 0.01). For the whole group of patients the lymph node metastatic rate was 28.5% in upper-thoracic esophageal cancer, significantly lower than 38.8% of the lower-thoracic esophageal cancer (P = 0.039) and 43.4% in the middle-thoracic esophageal cancer (P = 0.010). However, the lymph node metastatic rates were 37.0%, 37.9% and 41.4% in the upper-, middle- and lower-thoracic esophageal cancers of the 592 cases receiving left chest notches, with a non-significant difference among them (P = 0.715). CONCLUSION: The lesion length, depth of tumor invasion, vascular tumor embolus and distant metastasis are the most important parameters for lymph node metastases. Operative modes have obvious influence on the distribution of regional lymph node metastases. Therefore, in the clinical management, a postoperative prophylactic radiotherapy may be selected according to the tumor length, depth of tumor invasion, vascular tumor embolus and distant lymph node metastasis.

Prognostic value of circulating CD133(+) cells in patients with gastric cancer.

OBJECTIVES: Gastric cancer is an important cause of cancer-related mortality worldwide (1). There is increasing evidence that the existence of cancer stem cells (CSC) is responsible for tumour formation and maintenance. MATERIALS AND METHODS: The present study was designed to recognise circulating CSCs from blood samples of patients with gastric cancer, using CD133 and ABCG2 as potential markers. CD133(-) , CD133(+)  ABCG2(-) and CD133(+)  ABCG2(+) cells lines were analysed by flow cytometry, immunofluorescence staining, western blotting and real-time PCR. Furthermore, functional assays (clonogenic assay in vitro and tumourigenic assay in vivo) were also performed using these cell lines. RESULTS: Higher percentages of CD133(+) cells were identified in blood samples from gastric cancer patients compared to normal controls. In addition, we found by using Kaplan-Meier analysis, that numbers of CD133(+) cells correlated with poor prognosis gastric cancer patients. Finally, tumourigenic properties of CD133(+)  ABCG2(+) cells were determined in vitro and in vivo. CONCLUSIONS: Our in vitro and in vivo experiments demonstrated that CD133(+)  ABCG2(+) cells exhibited well-known CSC characteristics; thus when circulating they could be used as a prognostic marker for gastric cancer.