Jun Xiang

The Clinical Significance and Risk Factors of Solitary Lymph Node Metastasis in Gastric Cancer

Aims To assess the clinical significance and risk factors of solitary lymph node metastasis (SLM) in gastric carcinoma and establish a more accurate method to evaluate the possibility of lymph node metastasis (LM). Methods A total of 385 patients with gastric carcinoma who underwent D2 lymphadenectomy at the Cancer Center of Sun Yat-Sen University were included in this research. Then we used a group of data from Sun Yat-sen University Gastrointestinal Hospital (SYSUGIH) to validate the accuracy of our developed method. The χ2 test, Kaplan–Meier analysis, log-rank test, COX model, and discriminate analysis were used to analyze the data with SPSS13.0. Results We found that the LM number and pathological T staging were independent prognostic risk factors. CEA grading, LN status by CT, and T staging by CT were independent risk factors for LM in gastric carcinoma. In addition, we developed the equation Y = -5.0 + X 1 + 1.8X 3 + 0.7X 4 (X 1 = CEA grading, X 3 = LN status by CT, X 4 = T staging by CT) to evaluate the situation of LM. The data from SYSUGIH shows this equation has a better accuracy compared with CT. Conclusions SLM is an independent risk factor in gastric cancer. And there was no survival difference between the skip metastasis group and the other SLM group (P = 0.659). It is inappropriate for the patient with SLM doing a standard D2 lymphadenectomy, due to the fact that LM rarely occurs in the splenic artery, splenic hilum. The risk factors for LM include CEA grading, LN status by CT, and T staging by CT. And we can use Y = -5.0 + X 1 + 1.8X 3 + 0.7X 4 (X 1, CEA grading, X 3 = LN status by CT, X 4 = T staging by CT, the critical value is 0.3) to estimate the possibility of LM, which has a better accuracy compared with CT.

Levels of human replication factor C4, a clamp loader, correlate with tumor progression and predict the prognosis for colorectal cancer

BackgroundHuman replication factor C4 (RFC4) is involved in DNA replication as a clamp loader and is aberrantly regulated across a range of cancers. The current study aimed to investigate the function of RFC4 in colorectal cancer (CRC).MethodsThe mRNA levels of RFC4 were assessed in 30 paired primary CRC tissues and matched normal colonic tissues by quantitative PCR. The protein expression levels of RFC4 were evaluated by western blotting (n = 16) and immunohistochemistry (IHC; n = 49), respectively. Clinicopathological features and survival data were correlated with the expression of RFC4 by IHC analysis in a tissue microarray comprising 331 surgically resected CRC. The impact of RFC4 on cell proliferation and the cell cycle was assessed using CRC cell lines.ResultsRFC4 expression was significantly increased in CRC specimens as compared to adjacent normal colonic tissues (P <0.05). High levels of RFC4, determined on a tissue microarray, were significantly associated with differentiation, an advanced stage by the Tumor-Node-Metastasis (TNM) staging system, and a poor prognosis, as compared to low levels of expression (P <0.05). However, in multivariate analysis, RFC4 was not an independent predictor of poor survival for CRC. In vitro studies, the loss of RFC4 suppressed CRC cell proliferation and induced S-phase cell cycle arrest.ConclusionRFC4 is frequently overexpressed in CRC, and is associated with tumor progression and worse survival outcome. This might be attributed to the regulation of CRC cell proliferation and cell cycle arrest by RFC4.

MicroRNA-495 Inhibits Gastric Cancer Cell Migration and Invasion Possibly via Targeting High Mobility Group AT-Hook 2 (HMGA2)

Background Gastric cancer is one of the most common malignancies, and has a high mortality rate. miR-495 acts as a suppressor in some cancers and HMGA2 (high mobility group AT-hook 2) is a facilitator for cell growth and epithelial-mesenchymal transition (EMT), but little is known about their effect in gastric cancer. This study aimed to investigate the role and mechanism of miR-495 in gastric cancer. Material/Methods miR-495 levels were quantitatively analyzed in gastric cancer tissue and GES-1, SGC-7901, BGC-823, and HGC-27 cell lines by qRT-PCR. Levels of miR-495 and HMGA2 were altered by cell transfection, after which cell migration and invasion were examined by Transwell and E-cadherin (CDH1); vimentin (VIM), and alpha smooth muscle actin (ACTA2) were detected by qRT-PCR and Western blotting. The interaction between miR-495 and HMGA2 was verified by dual-luciferase reporter assay. Results miR-495 was significantly downregulated in cancer tissue and cell lines (p<0.05). Its overexpression inhibited cell migration and invasion, elevated CDH1, and inhibited VIM and ACTA2 levels in BGC-823 and HGC-27 cells. miR-495 directly inhibited HMGA2, which was upregulated in gastric cancer tissue, and promoted cell migration and invasion, inhibited CDH1, and elevated VIM and ACTA2. Conclusions miR-495 acts as a tumor suppressor in gastric cancer by inhibiting cell migration and invasion, which may be associated with its direct inhibition on HMGA2. These results suggest a promising therapeutic strategy for gastric cancer treatment.

Clinicopathological characteristics and long-term outcomes of colorectal cancer in elderly Chinese patients undergoing potentially curative surgery

PurposeThe aim of this study was to determine the clinicopathological characteristics and outcomes of Chinese colorectal cancer (CRC) patients aged 75xa0years and older undergoing potentially curative surgery.MethodsA total of 2,482 CRC patients at TNM stage I–III undergoing surgical treatment between 1995 and 2005 were evaluated, and patients were divided into a younger (<75xa0years old) and an elderly (≥75xa0years) group.ResultsThere were 2,482 CRC patients in this study, of which 2,194 (88.4xa0%) patients were in the younger group (mean age 57xa0years) and 288 (11.6xa0%) were in the elderly group (mean age 79xa0years). Significant differences were observed between the two groups with regard to the American Society of Anesthesiologists’ score, tumor location, co-morbidities, emergency procedures, use of chemotherapy, proportion admitted to the ICU, length of ICU stay, causes of death, T/N stage and postoperative recurrence. The postoperative mortality increased from 4.8xa0% in the younger group to 8.3xa0% in the older group (pxa0=xa00.011). Although significant differences were found in the overall 5-year survival (73 vs. 56xa0%, pxa0<xa00.0001) and disease-free 5-year survival (68 vs. 54xa0%, pxa0<xa00.0001) between the two groups, the cancer-specific 5-year survival was similar (88 vs. 85xa0%, pxa0=xa00.089) in both groups.ConclusionsAlthough elderly CRC patients have unique clinicopathological features, a higher postoperative mortality and a worse overall and disease-free survival compared with younger patients, the cancer-specific survival at five years is similar between elderly and younger patients. Elderly patients benefit from radical surgery and have a good postoperative oncological outcome, irrespective of their age.

Body mass index (BMI) may be a prognostic factor for gastric cancer with peritoneal dissemination

BackgroundThe aim of this study is to investigate whether body mass index (BMI) is a prognostic factor in gastric cancer patients with peritoneal dissemination.MethodsThis is a retrospective study consisting of 518 patients with a histological diagnosis of gastric cancer with peritoneal dissemination seen at the Sixth Affiliated Hospital of Sun Yat-Sen University and Sun Yat-sen University Cancer Center between January 2010 and April 2014. Patients were followed until December 2015. Chi-square test and Kaplan-Meier survival analysis were used to compare the clinicopathological variables and prognosis.ResultsUnivariate analyses showed that significant prognostic factors included palliative gastrectomy (pu2009<u20090.001), tumor size (pu2009<u20090.001), tumor location (pu2009=u20090.011), peritoneal seeding grade (pu2009<u20090.001), ascites (pu2009=u20090.001), serum CEA level (pu2009=u20090.002), serum CA19-9 level (pu2009=u20090.033), palliative chemotherapy (pu2009<u20090.001), and BMI group (pu2009<u20090.001). For patients with palliative chemotherapy, univariate analysis revealed that palliative gastrectomy (pu2009<u20090.001), tumor size (pu2009=u20090.002), tumor location (pu2009=u20090.024), peritoneal seeding grade (pu2009=u20090.008), serum CEA level (pu2009=u20090.041), and BMI group (pu2009<u20090.001). Multivariate analysis revealed that BMI was an independent prognostic factor in gastric cancer patients with peritoneal dissemination, especially in patients who received palliative chemotherapy.ConclusionsBMI is a prognostic factor for patients who have gastric cancer with peritoneal dissemination, especially in those who received palliative chemotherapy.

Nomogram analysis and external validation to predict the risk of lymph node metastasis in gastric cancer

Aim To identify risk factors for lymph node metastasis using a nomogram for gastric cancer patients to predict lymph node metastasis. Results The Chi-square test and the logistic regression showed that the Boarrmann type, preoperative CA199 level, T stage and N stage by CT scan were independent risk factors. The concordance index (C-index) was 0.786 in the internal validation of the Nomogram model. In the external validation, the C-index was 0.809, and the AUC was 0.894. The total accuracy of the prediction was 82.2%, and the false-negative rate was 5.4% with a cut-off value set at 0.109. Materials and Methods The study consisted of 451 patients with a histological diagnosis of gastric cancer with 0 or 1 lymph node metastasis from the Sun Yat-sen University Cancer Center as the development set, and the validation set consisted of 186 gastric cancer patients from the Sixth Affiliated Hospital of Sun Yat-Sen University. A Chi-square test and a logistic regression analysis were used to compare the clinicopathological variables and lymph node metastasis. The C-index and ROC curve were computed for comparisons of the nomograms predictive ability. Conclusions We developed and validated a nomogram to predict lymph node metastasis in gastric cancer before surgery. This nomogram can be broadly applied, even in general hospitals, and is useful for decisions regarding treatment programs for patients.

Low expression of CDK10 correlates with adverse prognosis in gastric carcinoma

Background: Cyclin-dependent kinase (CDK) 10, is reported to play an essential role in the progression from the G2 to M phase of the cell cycle. Recently, reduced expression of CDK10 has been observed in several cancerous human tissue, suggesting that CDK10 is a tumor suppressor gene. However, data on its expression pattern and clinical relevance in gastric cancer are not sufficient. Therefore, this study aims to investigate CDK10 expression and its prognostic significance in primary gastric adenocarcinoma. Methodology/Principal Findings: The expression level of CDK10 was analyzed using qRT-PCR, western blotting, and immunohistochemistry on tissue samples from 189 post-resection gastric cancer patients. The expression of CDK10 mRNA was reduced in tumor tissue samples compared with matched adjacent non-tumor tissue samples (P=0.013); this finding was confirmed by western blot analysis (P=0.016). Immunohistochemistry data indicated that CDK10 expression was significantly decreased in 92 of 189 (48.7%) gastric cancer cases. Kaplan-Meier survival curves revealed that decreased expression of CDK10 was strongly associated with a poor prognosis in gastric cancer patients (P<0.001). Multivariate Cox analysis identified CDK10 expression as an independent prognostic factor for overall survival (P=0.011). Conclusions/Significance: Our data suggest that reduced CDK10 expression independently predicts a poor prognosis in patients with gastric cancer. CDK10 can may serve as a valuable prognostic marker and a potential target for gene therapy.

A novel anti-reflux reconstruction after laparoscopic total gastrectomy: jejunal pouch-esophageal anti-reflux anastomosis

A novel anti-reflux reconstruction after laparoscopic total gastrectomy: jejunal pouch-esophageal anti-reflux anastomosis Shi Chen, Xi-Jie Chen, Dong-Wen Chen, Jun Xiang, Jun-Sheng Peng* Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China

Nuclear receptor binding protein 1 correlates with better prognosis and induces caspase-dependent intrinsic apoptosis through the JNK signalling pathway in colorectal cancer

Nuclear receptor binding protein 1 (NRBP1) is a ubiquitously expressed and highly conserved pseudokinase that has important roles in cellular homoeostasis. Despite recent advances in understanding the biology of NRBP1, the role of NRBP1 and its underlying mechanism in colorectal cancer (CRC) have not been fully elucidated. In the present study, we observed that NRBP1 expression levels were significantly reduced in CRC tissues compared with corresponding adjacent normal tissues, and high NRBP1 expression correlated with better prognosis in CRC. Overexpression of NRBP1 inhibited CRC cell proliferation and promoted apoptosis in vitro and in vivo. In contrast, knockdown of NRBP1 expression increased cell proliferation and decreased the percentage of apoptotic cells. Moreover, overexpression of NRBP1 activated caspase-dependent intrinsic apoptosis. In addition, we further discovered that NRBP1 regulated the apoptotic pathway through interaction with JNK. Finally, NRBP1 overexpression led to attenuated CRC growth in a xenograft mouse model. Our study illustrates the suppressor role of NRBP1 in CRC and provides a potential therapeutic target.

Tumor Size Is a Critical Factor in Adjuvant Chemotherapy for T3-4aN0M0 Gastric Cancer Patients after D2 Gastrectomy

Aim. To investigate whether tumor size is a reasonable indication for adjuvant chemotherapy for T3-4aN0M0 gastric cancer patients after D2 gastrectomy. Method. We performed a retrospective study of 269 patients with a histological diagnosis of T3-4aN0M0 stage gastric cancer who underwent D2 radical surgery at the Sun Yat-sen University Cancer Center or the Sixth Affiliated Hospital of Sun Yat-sen University between January 2006 and December 2010. The follow-up lasted until June of 2015. Chi-square tests and Kaplan-Meier methods were employed to compare the clinicopathological variables and prognoses. Result. For this group of patients, univariate analyses revealed that tumor size (p < 0.001), pathological T stage (p < 0.001), and tumor location (p = 0.025) were significant prognostic factors. Adjuvant chemotherapy did not exhibit prognostic benefits. For patients with tumors larger than 5u2009cm, univariate analysis revealed that tumor location (p = 0.007), Borrmann type (p = 0.039), postoperative chemotherapy (p = 0.003), and pathological T stage (p < 0.001) were significant prognostic factors. Multivariate analysis revealed that postoperative chemotherapy and pathological T stage were independent prognostic factors. Conclusion. Our results imply that tumor size should be a critical factor in the decision to utilize adjuvant chemotherapy for T3-4aN0M0 gastric cancer patients after D2 gastrectomy. Additional randomized controlled trials are required before this conclusion can be considered definitive.