Kun Zhu

Plasma miR-183 predicts recurrence and prognosis in patients with colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. The prognosis for this cancer is poor, and the development of novel biomarkers, particularly non-invasive surrogate biomarkers, is urgently needed. Recent studies have demonstrated that microRNAs (miRNAs) are stably detectable in the blood and can serve as useful biomarkers for various types of cancer. In this study, the miR-183 expression levels were found to be significantly overexpressed in plasma samples from CRC patients compared with controls, and the postoperative plasma miR-183 levels were significantly reduced compared with the preoperative levels. The value of the area under the receiver operating characteristic (ROC) curve obtained for miR-183 was 0.829, which was higher than those for carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). High plasma miR-183 expression was significantly associated with lymph node metastasis, distant metastasis, higher pTNM stage (III-IV), and tumor recurrence. CRC patients with elevated miR-183 expression in plasma displayed shorter disease-free survival (DFS) and lower overall survival (OS). More importantly, plasma miR-183 was independently correlated with tumor recurrence and a lower OS. Collectively, our results suggested that the elevated miR-183 in the plasma could be a promising biomarker for predicting the risk of tumor recurrence and poor survival in CRC patients.

The preoperative neutrophil–lymphocyte ratio predicts recurrence and survival among patients undergoing R0 resections of adenocarcinomas of the esophagogastric junction

Elevated preoperative neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) predict survival rates among patients with several types of cancer. The current study sought to clarify whether NLR and PLR are clinically useful independent prognostic indicators of adenocarcinomas of the esophagogastric junction (AEG) among patients undergoing curative resections (i.e., R0 resections).

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.

Adenocarcinomas of the esophagogastric junction: experiences at a single institution in China

BackgroundThe incidence of adenocarcinoma of the esophagogastric junction is increasing. This study aims to evaluate the clinicopathological features of Chinese patients with adenocarcinoma of the esophagogastric junction and to define prognostic factors.MethodsWe retrospectively reviewed a database of 382 consecutive patients with adenocarcinoma of the esophagogastric junction at the First Affiliated Hospital of Xi’an Jiaotong University from January 2005 to March 2010. All patients were classified according to the Siewert’s classification and staged according to the latest edition of the American Joint Committee on Cancer categories.ResultsSix of the 382 patients had type I adenocarcinoma, 220 had type II, and 156 had type III. There was no significant difference in the overall survival of different Siewert subtypes. According to the multivariate analysis, pathological lymph node stage, age, and the existence of lymphovascular invasion were the independent factors of prognosis of adenocarcinoma of the esophagogastric junction following surgery.ConclusionsOn the data, the distribution of the three types of tumor was found to be different from that reported in Western countries. Lymph node metastasis, lymphovascular invasion, and age were significant and independent factors for poor prognosis after R0 resection for adenocarcinoma of the esophagogastric junction.

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.

Paf15 expression correlates with rectal cancer prognosis, cell proliferation and radiation response.

Paf15, which participates in DNA repair, is overexpressed in numerous solid tumors. Blocking of Paf15 inhibits the growth of many types of cancer cells; while simultaneously enhancing cellular sensitivity to UV radiation. However, its expression and function in rectal cancer (RC) remain unknown. The current study was undertaken to assess the association of Paf15 expression with RC prognosis, as well as to explore the participation of Paf15 in the response of RC cells to irradiation. Increased Paf15 expression was observed in RC tissues and associated with pTNM stage and poor survival. In vitro, Paf15 induced increased RC cell proliferation while accelerating cell cycle progression, inhibiting cell death, and protecting against gamma radiation-induced DNA damage in RC cells. In conclusion, increased Paf15 expression is associated with increased RC proliferation, decreased patient survival, and a worse radiotherapeutic response.

MEG3/miR‑21 axis affects cell mobility by suppressing epithelial‑mesenchymal transition in gastric cancer

The prognosis of patients with gastric cancer remains poor mainly due to distant metastasis. Maternally expressed gene 3 (MEG3), a long non-coding RNA (lncRNA), is downregulated in various tumor tissues and suppresses tumor progression. miR-21 is a microRNA which is expressed highly in tumor tissues. In the present study, we investigated the relationship between MEG3 and miR-21 in regards to the cell mobility of gastric cancer. Our data demonstrated that MEG3 was downregulated while miR-21 was upregulated in gastric cancer tissues and cell lines by qRT-PCR. Overexpression of MEG3 suppressed cell mobility of gastric cancer cells (AGS) by downregulating the expression of MMP-3, MMP-9 and VEGF. As shown by western blot analysis, overexpression of MEG3 also suppressed epithelial-mesenchymal transition (EMT) by increasing the expression of an epithelial marker (E-cadherin) and downregulating the expression of mesenchymal markers (N-cadherin, Snail and β-catenin), indicating that MEG3 suppressed cell mobility through the inhibition of EMT in gastric cancer. The expression of miR-21 was negatively regulated by MEG3 and overexpression of miR-21 promoted cell mobility of AGS through activation of EMT. Co-transfection of lncRNA-MEG3 and miR-21 mimic counteracted the inhibitory effect on the cell mobility attributed to MEG3, suggesting that the MEG3/miR-21 axis affects cell mobility by suppressing EMT in gastric cancer. Using a mouse xenograft tumor model, we found that the overexpression of MEG3 suppressed tumor growth and metastasis while overexpression of miR-21 had the opposite effects. The MEG3/miR-21 axis affected gastric cancer growth and metastasis through inhibition of EMT in vivo. In conclusion, we demonstrated that the MEG3/miR-21 axis participates in the tumor progression and metastasis of gastric cancer through the regulation of EMT.