Higher Tumor Node Metastasis Stage Research Articles

Long noncoding RNA associated with microvascular invasion in hepatocellular carcinoma promotes angiogenesis and serves as a predictor for hepatocellular carcinoma patients' poor recurrence-free survival after hepatectomy

Survival of patients with hepatocellular carcinoma (HCC) remains poor, which is largely attributed to active angiogenesis. However, the mechanisms underlying angiogenesis in HCC remain to be discovered. In this study, we found that long noncoding RNA associated with microvascular invasion in HCC (lncRNA MVIH) (lncRNA associated with microvascular invasion in HCC) was generally overexpressed in HCC. In a cohort of 215 HCC patients, the overexpression of MVIH was associated with frequent microvascular invasion (P = 0.016) and a higher tumor node metastasis stage (P = 0.009) as well as decreased recurrence-free survival (RFS) (P < 0.001) and overall survival (P = 0.007). Moreover, the up-regulation of MVIH served as an independent risk factor to predict poor RFS. We also found that MVIH could promote tumor growth and intrahepatic metastasis by activating angiogenesis in mouse models. Subsequent investigations indicated that MVIH could activate tumor-inducing angiogenesis by inhibiting the secretion of phosphoglycerate kinase 1 (PGK1). Additionally, in 65 HCC samples, MVIH expression was inversely correlated with the serum level of PGK1 and positively correlated with the microvessel density. Deregulation of lncRNA MVIH is a predictor for poor RFS of HCC patients after hepatectomy and could be utilized as a potential target for new adjuvant therapies against active angiogenesis.

Pyrophosphatase overexpression is associated with cell migration, invasion, and poor prognosis in gastric cancer

Inorganic pyrophosphatase (PPase) catalyzes the hydrolysis of pyrophosphate to form orthophosphate. Pyrophosphate can substitute for ATP under certain circumstances. We previously conducted a proteomic analysis to investigate tumor-specific protein expression in gastric cancer, and PPase was identified as a potential gastric tumor-specific marker; it was therefore selected for further study. Clinicopathological analysis, using proteomic analysis and immunohistochemistry, was used to validate PPase as a prognostic marker in gastric cancers. Proteomic analysis showed that PPase was overexpressed in patients with lymph node (LN) metastases and high tumor node metastasis (TNM) stages (p < 0.05). Based on immunohistochemistry, patients whose tumors overexpressed PPase had higher T stages, LN metastasis, a higher TNM stage, a higher cancer recurrence rate, and shorter survival times than patients whose tumors exhibited PPase underexpression (p < 0.05). Gain-of-function and loss-of-function approaches were employed to examine the malignant phenotypes of PPase-overexpressing or PPase-depleted cells. A decrease in PPase expression caused a significant decrease in gastric cancer cell migration and invasion in vitro, whereas forced overexpression of PPase enhanced migration but not invasion. Our findings indicate that PPase is involved in gastric tumor progression and that PPase may be a useful marker for poor prognosis of human gastric cancers.

CCL7 and CCL21 overexpression in gastric cancer is associated with lymph node metastasis and poor prognosis

To investigate how a complex network of CC chemokine ligands (CCLs) and their receptors influence the progression of tumor and metastasis. In the present study, we used immunohistochemistry to examine the expression of CCL7, CCL8 and CCL21 in 194 gastric cancer samples and adjacent normal tissues. We analyzed their correlation with tumor metastasis, clinicopathologic parameters and clinical outcome. We found that the higher expression of CCL7 and CCL21 in cancer tissues than in normal tissues was significantly correlated with advanced depth of wall invasion, lymph node metastasis and higher tumor node metastasis stage. Moreover, Kaplan-Meier survival analysis revealed that CCL7 and CCL21 overexpression in cancer tissues was correlated with poor prognosis. These results suggest that overexpression of these two CC chemokine ligands is associated with tumor metastasis and serves as a prognostic factor in patients with gastric cancer.

Epidermal Growth Factor Receptor Expression in Esophageal Adenocarcinoma: Relationship with Tumor Stage and Survival after Esophagectomy

Background and Aims. Esophageal adenocarcinoma (EA) is an aggressive tumor with increasing incidence in occidental countries. Several prognostic biomarkers have been proposed, including epidermal growth factor receptor (EGFR). The aim of this study was to assess whether EGFR expression predicts EA staging and patient survival. Methods. In this historical cohort, consecutive patients with EA managed between 2000 and 2010 were considered eligible for the study. Surgical specimens of patients treated with transhiatal esophagectomy were evaluated to establish EGFR expression and tumor differentiation. Staging was classified according with tumor-node-metastasis (TNM) system. Survival was determined according to either medical register or patient's family contact. Results. Thirty-seven patients who underwent esophagectomy without presurgical chemotherapy or radiotherapy were studied. EGFR expression was found in 16 patients (43%). EGFR expression was more frequent as higher was the TNM (I and II = 0% versus III = 47% versus IV = 100%; P < 0.001). Average survival in months was significantly shorter in the group of patients with EGFR expression (10.5 versus 21.7; P = 0.001). Conclusions. In patients with esophageal adenocarcinoma treated with transhiatal esophagectomy, EGFR expression was related to higher TNM staging and shorter survival. EGFR expression might be assumed as a prognostic marker for esophageal adenocarcinoma.

Portal venous invasion: The single most independent risk factor for immediate postoperative recurrence of hepatocellular carcinoma

Despite improvements of treatment in hepatocellular carcinoma (HCC), the recurrence rate after curative hepatic resection still remains remarkably high. An immediate recurrence of HCC after surgery is frustrating. We tried to clarify risks of immediate postoperative recurrence of HCC; that is, within 4 months after curative hepatic resection. A total of 167 patients with HCC underwent hepatic resection; 60 had immediate postoperative recurrences (IPR group), and 107 had disease-free survival for more than 5 years (DFS group). Variables were compared between the two groups. Univariate analysis showed the following variables were significant risk factors for immediate postoperative recurrence of HCC: male sex, elevated serum aspartate aminotransferase level, greater amount of blood loss, longer operation time, worse tumor differentiation, higher tumor node metastasis stage, and presence of any of the following: intrahepatic metastasis, tumor-rupture, portal venous invasion, or microvascular invasion. In multivariate analysis, only portal venous invasion was a significant risk factor (odds ratio=3.2, P=0.03, standard error=0.5, Logistic regression analysis). Portal venous invasion may be the most significant risk factor for immediate postoperative recurrence of HCC. However, accurate assessment of this risk factor may require histological examination, limiting its utility as a preoperative predictor. Further research is necessary to definitively identify preoperative predictors.

MTSS1 Overexpression Correlates with Poor Prognosis in Colorectal Cancer

BackgroundThe aims of this study were to investigate metastasis suppressor 1 (MTSS1) expression in benign and malignant colorectal tissues and to explore its significance in the prognosis of colorectal cancer (CRC) patients. MethodsMTSS1 expression was detected by immunohistochemistry in CRC, colorectal adenomatous polyp (precancerous lesion) and normal colorectal tissues. The relationship between MTSS1 expression in CRC tissues and clinicopathologic factors was analyzed with Mann–Whitney U test. MTSS1 protein expression was observed by Western blot in CRC tissues and adjacent nontumor colorectal tissues. Two factors between MTSS1 expression and CRC patient tumor node metastasis (TNM) stage were analyzed by Spearman rank correlation analysis. The Kaplan–Meier method and log-rank test were employed to compare the overall survival between MTSS1 negative/weak positive expression group and MTSS1 strong positive expression group. ResultsMTSS1 expression rates were significantly higher in CRC tissues (99 out of 135, 73.30%) than that in normal colorectal tissues (one out of seven, 14.29%), nontumor colorectal tissues (six out of 32, 18.75%), and adenomatous polyp tissues (four out of 15, 26.67%; P = 0.003, P < 0.001, P = 0.001, respectively). The upregulated MTSS1 expression in CRC tissues was significantly correlated to poor differentiation (P = 0.005), tissue invasion (P = 0.018), high preoperative CEA level (P = 0.022), present lymph node metastasis (P = 0.003), and high TNM stage (P = 0.002). MTSS1 expression was positively correlated with clinical TNM stage, that suggested the more advanced clinical TNM stage corresponding to the higher expression level of MTSS1 (rs = 0.327, P < 0.05). Western blotting demonstrated that MTSS1 expression was upregulated in 25 of 32 CRC tissues (75.0%) compared to corresponding adjacent nontumor colorectal tissues. The overall 5-year survival of MTSS1 strong positive expression CRC patients was significantly shorter than that of MTSS1 negative and weakly positive expression group. In multivariate analysis, MTSS1 expression maintained independent prognostic influence on overall survival (P = 0.004). ConclusionMTSS1 may be a good biomarker to be applied in the clinical setting to predict the prognosis of CRC patients with completely resected.

Risk of recurrence after laparoscopy-assisted radical gastrectomy for gastric cancer performed by a single surgeon

The risk of recurrence after laparoscopy-assisted radical gastrectomy (LAG) was investigated. Clinical data of 398 consecutive patients who underwent radical gastrectomy with R0 resection for gastric cancer at Gyeongsang National University Hospital between January 2005 and December 2007 were reviewed retrospectively. Of the patients, 65.4% (n = 261) and 34.6% (n = 138) underwent LAG and open radical gastrectomy (OG), respectively. Of the LAG cases, 73.2% (n = 192), 10.7% (n = 28), 12.6% (n = 33), and 3.1% (n = 8) had stage I, II, III, and IV gastric cancer, respectively. All patients were followed up for a mean of 36.8 ± 13.7 months, and 14.6% (n = 58) had recurrence during the follow-up period. Univariate analysis revealed that tumor size, tumor-node-metastasis (TNM) stage, method of approach (LAG versus OG), and operation type were associated significantly with recurrence. Multivariate analysis revealed that only high TNM stage was significantly associated with recurrence (P = 0.00). While patients who underwent OG had higher incidence of recurrence than patients who underwent LAG, OG was not significantly associated with recurrence on multivariate analysis (P = 0.06). LAG and OG did not differ significantly in terms of recurrence, even when used in advanced gastric cancer cases. Multivariate analysis revealed that high TNM stage was significantly associated with recurrence. Thus, LAG appears to be a safe and feasible procedure that has the potential to be an alternative to open surgery, even for advanced gastric cancer.

Comparison of Laparoscopic and Open Gastrectomy on Cancer Cells Exfoliating From the Cancer-invaded Serosa

Whether laparoscopic gastrectomy may reduce the frequency of gastric cancer cells exfoliating from the cancer-invaded serosa remains unclear. This study aimed to compare the detection of free gastric cancer cells in the peritoneal cavity during laparoscopic and open gastrectomy. Intraoperative peritoneal washings were collected from 63 gastric cancer patients undergoing laparoscopic gastrectomy and 61 patients undergoing open surgery. Hematoxylin and eosin staining and real time reverse transcription-polymerase chain reaction were used to examine the free cancer cells. The postoperative positive rates of free cancer cells detected by cytologic and real time reverse transcription-polymerase chain reaction were 39.68% and 44.26% in the laparoscopic and open groups, respectively. The depth of tumor invasion, area of invaded serosa, regional lymph node involvement, and higher tumor node metastasis staging were significantly associated with the presence of free cancer cells. The laparoscopic techniques used in gastric cancer surgery were not associated with a greater risk for the intraperitoneal dissemination of cancer cells than conventional techniques.