Shu Qiang Yuan

Poor Prognosis of Gastric Adenocarcinoma with Decreased Expression of AHRR

Background The aryl hydrocarbon receptor (AHR) repressor (AHRR), a member of growing superfamily, is a basic-helix-loop-helix/Per-AHR nuclear translocator (ARNT)-Sim (bHLH-PAS) protein. Recently, AHRR has been proposed to function as a putative new tumor suppressor gene based on some relevant studies in multiple types of human cancers. This current study aims to investigate AHHR expression and its prognostic significance in primary gastric adenocarcinoma. Methodology/Principal Findings The expression level of AHRR was analyzed using real-time quantitative PCR (RT-qPCR), western blotting, and immunohistochemical staining. It was clearly showed that the expression status of AHRR was reduced in tumor tissue samples compared with that in matched adjacent non-tumor tissue samples by RT-qPCR (P = 0.0423) and western blotting analysis (P = 0.004). Moreover, data revealed that AHRR without exon 8 (the active isoform) was the predominant form either in tumor tissues (66.7%, 8/12) or in matched adjacent non-tumor tissues (100.0%, 12/12), and the mRNA level of this isoform was significantly reduced in tumor tissues (P = 0.006). Immunohistochemistry analysis indicated that AHRR expression was significantly decreased in 175 of 410 (42.7%) gastric adenocarcinoma cases. Kaplan-Meier survival curves and Multivariate Cox analysis revealed that decreased expression of AHRR was significantly associated with poor prognosis in gastric adenocarcinoma patients. Conclusions/Significance Our data suggests that, in primary gastric adenocarcinoma, AHRR may play as a suppressor gene and its expression status has the potential to be an independent prognostic factor.

Reduced expression of uroplakin 1A is associated with the poor prognosis of gastric adenocarcinoma patients.

Background The aim of this study was to investigate the expression and prognostic significance of Uroplakin1A (UPK1A) in gastric adenocarcinoma patients. Functional studies were also analyzed in vitro. Methodology/Principal Findings Real-time quantitative PCR (RT-qPCR), western blotting, and immunohistochemical (IHC) staining methods were used to analyze the expression of UPK1A in primary gastric adenocarcinoma tissue samples. Compared with matched adjacent non-tumor, the expression of UPK1A in fresh surgical specimens was reduced, which was confirmed by RT-qPCR (P<0.01) and western blotting analysis (P<0.01). The paraffin specimens from a consecutive series of 445 gastric adenocarcinoma patients who underwent surgery between 2003 and 2006 were analyzed by IHC staining. The relationship between UPK1A expression, clinicopathological factors, and survival were evaluated. IHC staining analysis revealed that the reduced expression of UPK1A was observed in 224 cases (50.3%). Additionally, the correlation analysis of clinicopathological factors demonstrated that reduced expression of UPK1A was significantly associated with histological grade (P = 0.022), node metastasis (P<0.001) and tumor node metastasis (TNM) stage (P = 0.008) (7th edition of the International Union Against Cancer (UICC)). Furthermore, Kaplan-Meier survival analysis revealed that the reduced expression of UPK1A was significantly associated with poor prognosis (P = 0.043). Cox hazards model analysis indicated that UPK1A expression was an independent risk factor at the 0.1 level (P = 0.094). The function of UPK1A in cell cycle, migration, and invasion was investigated by overexpressing UPK1A in the MKN45 gastric cancer cell line. The elevated expression of UPK1A cells induced G1 phase arrest and significantly inhibited migration and invasion. Conclusions/Significance The reduced expression of UPK1A might play a role in the progression of gastric cancer. Thus, UPK1A could be a potential favorable biomarker associated with gastric cancer prognosis.

Endoscopic ultrasonography compared with multidetector computed tomography for the preoperative staging of gastric cancer: A meta-analysis

BackgroundThe current study sought to perform a meta-analysis to compare the preoperative staging of endoscopic ultrasonography (EUS) and multidetector computed tomography (MDCT) in gastric carcinoma.MethodsArticles published between January 1, 2000, and April 1, 2016, that compared EUS with MDCT were included, and data were presented as 2 × 2 tables. The sensitivities, specificities and summary receiver operating characteristic (ROC) curves for T and N staging were calculated using a bivariate mixed effects model. Data were weighted by generic variance and then pooled by random-effects modeling.ResultsEight studies comprising 1736 patients were included in this meta-analysis. For T1 staging, the sensitivity value for EUS (82%) was significantly higher than that for MDCT (41%) (relative risk (RR): 2.06, 95% confidence interval (CI) 1.07–3.94; P = 0.030). For lymph node involvement, the sensitivity value for EUS (91%) was also significantly higher than that for MDCT (77%) (RR 1.14, 95% CI 1.05–1.23; P = 0.001). However, the specificity values of both EUS and MDCT were quite low, at 49 and 63%, respectively. No significant differences in T2–4 staging between EUS and MDCT were noted.ConclusionThis meta-analysis indicates that EUS may be superior to MDCT in preoperative T1 and N staging. Additionally, the low specificity values of EUS and MDCT for N staging merits attention.

Clinicopathological characteristics and prognostic value of signet ring cells in gastric carcinoma: A meta-analysis

Background and Objectives: Previous studies of the prognostic value of the signet ring cell (SRC) type have yielded inconsistent results. Therefore, the aim of the present meta-analysis is to explore the clinicopathological characteristics and prognostic value of SRCs. Methods: Relevant articles that compared SRC and non-SRC type in PubMed and Web of Science were comprehensively searched. Then, a meta-analysis was performed. Results: A total of 19 studies including 35947 cases were analyzed. Compared with non-SRC patients, SRC patients tended to be younger (WMD: -3.88, P=0.001) and predominantly female (OR: 1.60, P<0.001). Additionally, SRC patients exhibited less upper third tumor location (OR: 0.62, P<0.001) and less frequent hematogenous metastasis (OR: 0.41, P<0.001). There was no difference in overall survival (OS) between SRC and non-SRC patients in the total population (HR: 1.02, P=0.830). Early gastric cancer with SRCs was associated with better OS (HR: 0.57, P=0.002), while advanced gastric cancer with non-SRCs was associated with a worse prognosis (HR: 1.17, P<0.001). Conclusions: This meta-analysis revealed that SRC tends to affect young females and tends to be located in the middle and lower third of the stomach. Early SRCs are associated with better prognoses, while advanced SRCs are associated with worse prognoses.

Glasgow Prognostic Score is superior to ECOG PS as a prognostic factor in patients with gastric cancer with peritoneal seeding

The Glasgow Prognostic Score (GPS) has been shown to be associated with survival rates in patients with advanced cancer. The present study aimed to compare the GPS with the Eastern Cooperative Oncology Group Performance Status (ECOG PS) in patients with gastric cancer with peritoneal seeding. For the investigation, a total of 384 gastric patients with peritoneal metastasis were retrospectively analyzed. Patients with elevated C-reactive protein (CRP; >10 mg/l) and hypoalbuminemia (<35 mg/l) were assigned a score of 2. Patients were assigned a score of 1 if presenting with only one of these abnormalities, and a score of 0 if neither of these abnormalities were present. The clinicopathologic characteristics and clinical outcomes of patients with peritoneal seeding were analyzed. The results showed that the median overall survival (OS) of patients in the GPS 0 group was longer, compared with that in the GPS 1 and GPS 2 groups (15.50, vs. 10.07 and 7.97 months, respectively; P<0.001). No significant difference was found between the median OS of patients with a good performance status (ECOG <2) and those with a poor (ECOG ≥2) performance status (13.67, vs. 11.80 months; P=0.076). In the subgroup analysis, the median OS in the GPS 0 group was significantly longer, compared with that in the GPS 1 and GPS 2 groups, for the patients receiving palliative chemotherapy and patients without palliative chemotherapy. Multivariate survival analysis demonstrated that CA19-9, palliative gastrectomy, first-line chemotherapy and GPS were the prognostic factors predicting OS. In conclusion, the GPS was superior to the subjective assessment of ECOG PS as a prognostic factor in predicting the outcome of gastric cancer with peritoneal seeding.

Preoperative apolipoprotein B/apolipoprotein A1 ratio: A novel prognostic factor for gastric cancer

Background The correlations between lipid profile (lipid molecules and their derivative indexes) and clinical outcome have been widely testified in many carcinomas, but its prognostic value remains unknown in gastric cancer (GC). Our purpose in the study was to comprehensively evaluate the clinical significance of lipid profile in GC. Methods We retrospectively collected clinical information of 1,201 GC patients who received surgery at Sun Yat-sen University Cancer Center from 2005 to 2010. Kaplan–Meier analysis and Cox proportional hazards regression model were performed to determine its prognostic significance. Results Lipid profile including cholesterol, triglyceride, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), LDL-C/HDL-C ratio, and ApoB/ApoA1 ratio were analyzed. For the first time, we found ApoB/ApoA1 ratio showed the biggest prognostic potency among all lipid-related variables and could act as an independent prognostic factor in GC. Patients with a high ApoB/ApoA1 ratio (≥1) had a shorter overall survival (hazard ratio: 1.373, 95% confidence interval: 1.123–1.68; P=0.002). Conclusion Preoperative serum ApoB/ApoA1 ratio might be used as a novel prognostic indicator of GC.

Selective gastric cancer patients with peritoneal seeding benefit from gastrectomy after palliative chemotherapy: A propensity score matching analysis

Background: The present study aimed to explore whether gastric cancer patients with peritoneal seeding after receiving palliative chemotherapy could benefit from gastrectomy and to identify patients with peritoneal seeding who should be selected to receive gastrectomy. Methods: A total of 201 gastric cancer patients were diagnosed with peritoneal seeding and received palliative chemotherapy. Propensity score matching (PSM) was performed to balance the selection bias. Results: After PSM, compared with non-gastrectomy group, gastrectomy group had a longer median overall survival (OS) (23.60 vs. 13.80 moths; P=0.034). Patients with R0 resection had a median OS of 43.60 months compared with 11.27 months in patients who underwent R1/2 resection (P<0.001). The median OS times between the R1/2 resection and non-gastrectomy groups were not different (P=0.139). Subgroup analysis revealed that only patients receiving more than 4 periods of first-line chemotherapy benefited from gastrectomy (P=0.018), whereas patients receiving 1-4 periods of first-line chemotherapy did not (P=0.275). Multivariate analysis showed that gastrectomy (P=0.012) and the period of first-line chemotherapy (P<0.001) were independent prognostic factors. The overall postoperative morbidity was 3.03% (1/33) in the gastrectomy group, and no treatment-related death was observed. Conclusions: The present study indicated that gastrectomy after palliative chemotherapy is a safe procedure and showed a survival benefit for gastric cancer patients with peritoneal seeding. Moreover, clinically curative R0 gastrectomy and more than 4 periods of palliative chemotherapy resulted in better clinical outcomes.

Development and validation of a nomogram to predict the benefit of adjuvant radiotherapy for patients with resected gastric cancer

Background: The US guidelines for gastric cancer (GC) recommend adjuvant radiotherapy (ART) combined with 5-fluorouracil as a standard treatment for patients with resected locally advanced GC. However, patient selection criteria for optimizing the use of adjuvant therapies are lacking. In this study, we developed and validated a nomogram to predict the individualized overall survival (OS) benefit of ART among patients with resected ≥stage IB GC. Patients and Methods: The 2002-2006 Surveillance, Epidemiology, and End Results (SEER) data of 5,206 patients with resected GC were used as a training set for the development of a nomogram. The 2007-2008 SEER data of 1,986 patients with resected GC were used as validation data. Results: In the multivariate analysis weighted by inverse propensity score, the efficacy of ART varied by the ratio of positive to examined nodes (Pinteraction<0.01). The magnitude of this difference was included in the nomogram with associated prognosticators to predict the 3- and 5-year OS with and without ART. The nomogram showed significant prognostic superiority to the 8th TNM staging in the training set (Concordance index, 0.68 versus 0.65; P<0.01) and the validation set (Concordance index, 0.68 versus 0.64; P<0.01). Moreover, the calibration was accurate, and the actual efficacy of ART was positively correlated with the nomogram-estimated survival benefit from ART (Pinteraction<0.01 and Pinteraction=0.02 in the training set and the validation set, respectively). Conclusion: The nomogram can aid individualized clinical decision making by estimating the 3- and 5-year OS and potential benefits of ART among patients with resected GC.

High expression level of T-box transcription factor 5 predicts unfavorable survival in stage I and II gastric adenocarcinoma

The expression of T-box transcription factor 5 (TBX5) has previously been observed in human cancer. The aim of the present study was to investigate TBX5 expression and its potential clinical significance in gastric cancer (GC). Using reverse transcription-quantitative polymerase chain reaction, the TBX5 mRNA expression levels in 30 pairs of surgically resected healthy gastric tissues and early stage (stages I and II) GC tissues were evaluated. The TBX5 mRNA expression levels were increased in GC stage I and II tumor tissues (P=0.01, n=30) compared with the matched adjacent non-tumor tissue. However, no significant difference was observed in TBX5 mRNA expression levels in matched adjacent non-tumor tissue compared with the tumor tissue from stage III and IV GC samples (P=0.318, n=30). Immunohistochemical analysis for TBX5 expression was performed on 161 paraffin-embedded stage I and II GC tissue blocks. Statistical analysis was performed to evaluate the associations between TBX5 expression, clinicopathological factors and prognosis. Patients with stage I and II GC and tumors with high TBX5 expression levels presented poor overall survival (OS) rate (P=0.024). The Cox proportional hazards model analysis demonstrated that TBX5 expression was an independent risk factor (P=0.017). The present study indicates that high expression of TBX5 is associated with unfavorable OS rates in patients with stage I and II GC. In conclusion, the expression of TBX5 may be a valuable biomarker for the selection of cases of high-risk stage I and II GC.