Dongmei Diao

D-dimer: not just an indicator of venous thrombosis but a predictor of asymptomatic hematogenous metastasis in gastric cancer patients.

Background Plasma D-dimer levels have been shown to be high in advanced tumor stage patients and can be used to predict clinical outcome in cancer patients. As most advanced tumor stage patients exhibit asymptomatic metastasis, which contributes to early tumor recurrence after surgery, we hypothesized that plasma D-dimer levels can be used to predict patients with potential metastasis. Methods We enrolled 1042 primary gastric cancer patients in three multiple cancer centers in Northwest China and examined plasma D-dimer levels using the latex-enhanced immunoturbidimetric assay (LEIA) method. Plasma D-dimer levels were compared with the clinicopathological characteristics in this large-scale case-control study with follow up. We also performed regular follow-up studies for 395 patients to analyze the 2-year survival rate and early tumor recurrence. Results In this large-scale clinical study, we found that plasma D-dimer levels were increased in patients with distant metastasis and especially hematogenous metastasis patients. The cut-off value of the D-dimer levels was determined to be 1.5 mg/ml based on the ROC curve, and the sensitivity and specificity for metastasis prediction were 61.9% and 86.6%, respectively. Additionally, patients with high D-dimer levels displayed early tumor recurrence and poor outcome during the follow-up study. Conclusion Plasma D-dimer may represent an easy to measure and lower cost marker for the testing of gastric cancer patients to predict asymptomatic hematogenous metastasis.

Prognostic value of the D-dimer test in oesophageal cancer during the perioperative period

There has been little research on the perioperative D‐dimer levels in oesophageal cancer patients. Plasma D‐dimer levels can be used to predict the outcome in cancer patients.

Elevated KIAA0101 expression is a marker of recurrence in human gastric cancer

Gastric cancer (GC) is one of the most common malignant tumors with a high rate of recurrence, which results in surgery being unsuccessful. Therefore, it is important to find the reason for the surgery failing. The purpose of the present study was to investigate a factor related to recurrence. Expression of KIAA0101 was assessed in 61 paired human primary GC and non‐cancerous gastric tissue using immunohistochemistry. After surgery, all 61 patients were followed regularly for more than 24 months or until death to analyze the 2‐year survival rate and recurrence. After suppressing KIAA0101 by RNA interference in human GC cell lines, the cell viability was detected using MTT. We are first to find that KIAA0101 was elevated in GC tissues compared with paired non‐cancerous gastric tissues. Immunohistochemical staining also revealed the predominant nuclear localization of KIAA0101 protein. Despite these findings, GC patients with elevated KIAA0101 expression levels exhibited a high recurrence and subsequently poor prognosis in the survival study. Also, cell viability was significantly inhibited after suppressing KIAA0101 in GC cells, suggesting that KIAA0101 might promote cancer cell proliferation. KIAA0101 is increased in human GC and is a marker of recurrence.

Proliferation Enhanced By NGF-NTRK1 Signaling Makes Pancreatic Cancer Cells More Sensitive To 2DG-Induced Apoptosis

Rapidly proliferating cancer cells rely on increased glucose consumption for survival. The glucose analog 2-deoxy-D-glucose (2DG) cannot complete glycolysis and inhibits the growth of many types of cancers. It is unknown whether reduced glycolysis inhibits the growth of pancreatic cancer. Activation of nerve growth factor (NGF)-neurotrophic tyrosine kinase receptor type 1 (NTRK1) signaling leads to enhanced proliferation of these cells. We investigated the effect of 2DG treatment on the viability of NTRK1-transfected pancreatic cancer cells. After treatment with 2DG, the viability of pancreatic cancer cells was evaluated by MTT assay. SB203580 (a specific inhibitor of the p38-MAPK pathway) and PD98059 (an MAP2K1 [mitogen-activated protein kinase kinase 1, previously, MEK1] inhibitor) were used to inhibit p38-MAPK and ERKs, respectively. The percentage of apoptotic cells was determined by flow cytometry. Overexpression of NTRK1 in pancreatic cancer cells resulted in increased cell proliferation, which was reduced by PD98059-mediated inhibition of ERKs but not by suppression of p38-MAPK with SB203580. After treatment with 2DG, the percentage of apoptotic cells was greater in those with high expression of NTRK1 than in cells with low NTRK1 expression. Blocking the p38-MAPK pathway with SB203580 effectively abolished the apoptosis induced by 2DG. We conclude that pancreatic cancer cells with a high expression of NTRK1 are more sensitive to 2DG-induced apoptosis, through the p38-MAPK pathway.

Expression of KIAA0101 protein is associated with poor survival of esophageal cancer patients and resistance to cisplatin treatment in vitro

The KIAA0101 protein is overexpressed in various human cancers, including esophageal cancer (EC). This study assessed the association of KIAA0101 protein with prognosis and resistance to chemotherapy in EC patients and then explored the role of KIAA0101 in EC cells in vitro. A total of 228 EC patients participated in the study. Tissue samples were collected for immunohistochemical analysis of KIAA0101 expression in tumor and normal tissues for association with clinicopathological and survival data. KIAA0101 cDNA or shRNA were transfected into EC cells for assessment of tumor cell viability, sensitivity to cisplatin treatment, and gene expression. Array-based comparative genomic hybridization (aCGH) was used to detect the changed copy-number alterations in cell lines expressing different levels of KIAA0101. Expression of KIAA0101 protein was upregulated in EC tissues, which was associated with pTNM stage, resistance to chemotherapy, tumor recurrence, and poor survival of EC patients. In vitro experiments showed that expression of KIAA0101 enhanced cell proliferation and upregulated cyclins A and B expression, leading to a reduced G1 phase of the cell cycle. KIAA0101 also induced resistance of EC Eca-109 and TE-1 cell lines to cisplatin treatment through a decrease in apoptosis. The aCGH data showed that levels of KIAA0101 expression altered chromosome stability, affecting genes that are associated with cancer progression. In conclusion, upregulated KIAA0101 expression is associated with EC progression, resistance to chemotherapy, and poor survival of the patients.

Ratio of Metastatic to Examined Lymph Nodes, a Helpful Staging System and Independent Prognostic Factor of Esophagogastric Junction Cancer

Background The incidence of the esophagogastric junction cancer is growing rapidly. The purpose of this study is to clarify the outcome of the ratio between metastatic and examined lymph nodes in esophagogastric junction cancer patients with or without 7 examined lymph nodes. Methods A total of 3,481 patients who underwent operation are identified from the Surveillance, Epidemiology, and End Results database. Different lymph nodes resected groups are analyzed to test the lymph nodes ratio factor. Results There are 2522 patients with 7 or more lymph nodes resected and 959 patients with less than 7 lymph nodes resected. Lymph nodes ratio and lymph node involvement are independent prognostic factors. But the lymph nodes ratio categories have a better prognostic value than the lymph node involvement categories. Compared with lymph node involvement categories, lymph nodes ratio categories represent patients with more homogeneous overall survival rate. Conclusions This study defines that the lymph nodes ratio is an independent prognostic factor for esophagogastric junction cancer. The lymph nodes ratio can prevent stage migration and may be a helpful system to predict the prognosis of esophagogastric junction cancer patients.

Plasma D-dimer level in the perioperative period in non-small-cell lung cancer

Background:  There has been little research on perioperative hypercoagulability in non‐small‐cell lung cancer patients. The D‐dimer can be used to evaluate the hypercoagulability in cancer patients.

Relationships between p14ARF Gene Methylation and Clinicopathological Features of Colorectal Cancer: A Meta-Analysis.

We conducted a meta-analysis to explore the relationships between p14ARF gene methylation and clinicopathological features of colorectal cancer (CRC). Databases, including Pubmed, Embase and Cochrane Library, were searched and, finally, a total of 18 eligible researches encompassing 1988 CRC patients were selected. Combined odds ratios (ORs) with 95% confidence intervals (95% CIs) were evaluated under a fixed effects model for absence of heterogeneity. Significant associations were observed between p14ARF gene methylation and tumor location (OR = 2.35, 95% CI: 1.55–3.55, P = 0.001), microsatellite instability (MSI) status (OR = 3.28, 95% CI: 2.12–5.07, P<0.0001). However, there were no significant associations between p14ARF gene methylation and tumor stage, tumor differentiation. We concluded that p14ARF gene methylation may be significantly associated with tumor location, and MSI status of CRC.

[Pre-operative plasma D-dimer level may predict the poor prognosis within one year after the surgery for non-small cell lung cancer].

BACKGROUND AND OBJECTIVE Some operable non-small cell lung cancer (NSCLC) patients have poor prognosis shortly after the surgery. D-dimer (DD) is an independent prognosis factor of lung cancer, especially for inoperable patients. The aim of the study is to investigate whether the pre-operative plasma DD level could predict the poor prognosis shortly after the surgery in operable NSCLC patients. METHODS The pre-operative plasma DD level of 56 newly diagnosed NSCLC patients without metastasis was examined. All the patients had been followed for one year post-operatively and the end-point was the occurrence of the poor prognosis incident including any sign of the metastasis, local recurrence or death related with the lung cancer. Difference of prognosis according to pre-operative plasma DD level was compared by Chi-square test. Diseases progress was analyzed by Kaplan-Meier method. RESULTS Among 56 NSCLC patients, 91% had received the curative resections (44 lobectomy and 7 pneumonectomy). There were still 2 cases of the wedge resection and 3 cases of the exploration. The median of the pre-operative plasma DD level was 1.05 (0.55) mg/L. The patients were allocated into two subgroups by the median of the DD levels. There were 11 patients with poor prognosis within one year after the resection in the high DD subgroup, while 3 patients in the low DD subgroup (P=0.03, OR=4.89, 95%CI: 1.2-20.1). The diseases progress curves were significantly different between the high and low subgroups (P=0.024). Based on plasma DD level, the poor prognosis incident within one year after the surgery was best predicted in the early stage (I, II) of the NSCLC, especially in adenocarcinoma patients. CONCLUSION The pre-operative plasma DD levels may predict the poor prognosis within one year after the surgery in NSCLC. The measurement of the fibrinolysis marker may help to exclude the unfit patients for the surgery.

The Management and Prognostic Prediction of Adenocarcinoma of Appendix

Malignant tumours of the appendix are quite rare, especially appendiceal adenocarcinomas, which may be difficult to detect preoperatively or intraoperatively. We collected data for 1404 patients with adenocarcinoma of the appendix from the Surveillance, Epidemiology, and End Results Program (SEER) database to explore the potential associations between clinicopathological factors and overall survival. Furthermore, a novel nomogram for predicting prognosis was developed based on our analysis of the SEER data. The nomogram prediction model included seven prognostic factors derived based on different clinical estimates. When compared with the traditional tumour-node-metastasis (TNM) staging system, the nomogram prediction model showed superior discriminatory power (Harrell’s C-index, 0.741 vs. 0.686) and a greater degree of similarity to actual 5-year overall survival after calibration (Akaike Information Criterion index, 5270.781 vs. 5430.141). Finally, we provide recommendations for the management of patients with adenocarcinoma of the appendix. Notably, we found the depth of adenocarcinoma invasion may be used as an indicator to determine the optimal surgical approach. For mucinous adenocarcinomas of the appendix, because these tumours are characterized by unique biological behaviour, intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is recommended. However, whether systematic chemotherapy should be administered to patients with adenocarcinoma of the appendix requires further investigation.