Low expression of PDHA1 predicts poor prognosis in gastric cancer

PDH E1 component subunit alpha (PDHA1) has been reported to be biologically significant in several human tumors. The aim of this study was to investigate the expression of PDHA1 in gastric cancer (GC) and its relationship with clinicopathological characteristics and prognosis. Oncomine analysis of neoplastic vs. normal tissue showed that the mRNA levels of PDHA1 were significantly underexpressed in different types of GC across three analyses. Underexpression of PDHA1 was found in intestinal-type GC (P?=? 0.009), diffuse-type GC (P?=? 0.036), and mixed-type GC (P?=? 0.025). Immunohistochemical staining of the 174 GC tissue microarray showed that PDHA1 staining is much stronger in normal mucosa than in GC samples (P?=? 0.040). Furthermore, PDHA1 expression levels were found to be significantly lower in 69.05% (87/126) of poorly differentiated GCs as compared to the well or moderately differentiated ones (P?=? 0.037). Intriguingly, PDHA1 expression was significantly correlated with depth of invasion (P?<? 0.001), lymph node metastasis (P?<? 0.001), TNM stage (P?<? 0.001), and nerve invasion (P?=? 0.006). However, it was not correlated with gender, age, Lauren classification, and lymphovascular invasion (P > 0.05 for all). Kaplan-Meier analysis revealed that low tumor expression of PDHA1 was significantly correlated with a poorer overall survival in patients with GC (5-year overall survival rates for patients with low vs high PDHA1 expression?=?49.8% vs 72.7%, hazard ratio of death from GC?=?2.594, 95% CI?=?1.527 to 4.408, P?<? 0.001). Multivariate analysis showed that PDHA1 (P?=? 0.025) was an independent predictor of overall survival. These findings are of potential clinical utility and merit further validation.     

胃腺癌IGFBP4的表达与患者预后的关系

目的探讨胃腺癌中胰岛素样生长因子结合蛋白4(IGFBP4)的表达情况及预后意义。方法免疫组织化学技术检测2000年1月至2006年12月间401例胃癌术后标本中IGFBP4的表达,并探讨IGFBP4表达与临床病理参数及预后相关性。结果结果显示401例患者中208例(51.9%)IGFBP4表达下调,且在低分化胃腺癌、T4a/b、及Ⅲ/Ⅳ期胃癌患者中表达下调明显。生存分析显示IGFBP4低表达与较差的预后相关(P<0.001)。多因素分析显示IGFBP4可作为一个独立预后风险因素(HR=2.175,P<0.001)。结论 IGFBP4在胃腺癌中表达下调,提示预后不良。     

Clinicopathological and prognostic significance of C/EBP homologous protein (CHOP) in advanced gastric cancer

Background

Few studies have reported the clinical and prognostic significance of C/EBP homologous protein (CHOP) in advanced gastric cancer (GC). Therefore, the present study investigated the expression of CHOP in advanced GC patients to determine its potential prognostic role.

Correlation of cadherin-17 protein expression with clinicopathological features and prognosis of patients with sporadic gastric cancer

This study aimed to explore the correlations between cadherin-17 (CDH17) protein expression and the clinicopathological features and prognosis of patients with sporadic gastric cancer (GC). Nine relevant studies of 1,960 patients were identified using electronic database searches supplemented with a manual search in strict accordance with inclusion and exclusion criteria. Statistical analyses were conducted using STATA 12.0 statistical software. Relative risks and 95% confidence intervals were determined, and Z test was used to measure the significance of the overall effect size. A total of nine eligible cohort studies were included in this meta-analysis. The expression of CDH17 in patients with diffuse GC was significantly higher than in those with intestinal-type GC. Moreover, the tumor depth of invasion differed significantly between patients with positive CDH17 (CDH17+) and negative CDH17 (CDH17-) GC. However, there were no significant differences between CDH17+ and CDH17- GC patients with respect to tumor node metastasis clinical stages, histological grades, or lymph node metastasis. Despite the differences in invasive depth, there was no significant difference in 5-year survival rates between CDH17+ and CDH17- GC patients. Our meta-analysis provides evidence that CDH17 protein expression may be associated with the development of GC, suggesting that CDH17 is an important biomarker that could be useful for the early diagnosis of GC. However, CDH17 levels do not appear to impact overall survival.     

Advanced gastric cancer and prognosis

Summary The morphological features of 158 gastric carcinomas were analyzed in an attempt to identify patterns best correlated with prognosis. To this end, the depth of infiltration, vascular invasion, intra- and perineoplastic lymphocytic infiltrate, lymph node metastases and number of metastatic lymph nodes were evaluated according to the several classifications for advanced gastric cancer. A good correlation between prognosis and histological features of malignancy were observed, as well as different five-year survival rates for Mulligan, Lauren and Ming histotypes However, when the influence of each single morphological criteria of malignancy was examined, these differences disappeared for Mulligan and Lauren histotypes. On the other hand, the better prognosis for Ming expanding type carcinomas appeared unrelated to any individual feature of malignancy.     

Elevated epiregulin expression predicts poor prognosis in gastric cancer

Epiregulin (EREG) is a novel family member of EGF-like ligands and have elevated expression in a variety of human cancers. EREG expression promotes tumor progression and metastasis and reduces patient survival. However, the expression of EREG and its prognostic value are not clear in gastric cancer (GC). We assessed EREG mRNA and protein expression in GC tissues from Chinese patients using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining of tissue microarray, and analyzed the correlation between the level of EREG expression and patient clinical characteristics and prognosis. We found that EREG expression was significantly higher in GC tissues than in matched adjacent noncancerous tissues. High EREG protein expression in GC was significantly associated with TNM stage including tumor size, lymph node metastases and distant metastases as well as poor overall survival. These finding demonstrate that EREG is an independent prognostic biomarker for GC.     

Vimentin immunohistochemical expression as a prognostic factor in gastric cancer: A meta-analysis

Objective

The prognostic value of vimentin expression in Gastric Cancer (GC) has been assessed for years while the results are still in dispute. Thus, we performed a meta-analysis to determine the effect of vimentin immunohistochemical (IHC) expression on the prognosis of GC.

Inorganic pyrophosphatase (PPA1) is a negative prognostic marker for human gastric cancer

Inorganic pyrophosphatase (PPA1) is an enzyme which has been found to be upregulated in various tumors, yet its profile in gastrointestinal cancers has not systemically investigated. In present study, gastrointestinal tissue microarrays were used to evaluate PPA1 expression and the association of PPA1 expression with clinical outcomes was determined for patients with gastric cancer by immunohistochemistry. Overexpression of PPA1 was observed in cancers of the esophagus, stomach, and pancreaticobiliary system. PPA1 was overexpressed in 143 cases (51.3%) of the 279 primary gastric tumors and was associated with larger size (> 3 cm), nodal metastasis and advanced clinical staging (P < 0.05). Moreover, survival analysis demonstrated that PPA1 expression was significantly correlated reduced overall of patients with gastric cancer. Therefore, PPA1 may serve as a potential biomarker of poor prognosis in patients with gastric cancer.     

Down-regulation of long non-coding RNA LET is associated with poor prognosis in gastric cancer

Introduction: Long non-coding RNAs (lncRNAs) have emerged recently as major players in tumor biology and may be used for cancer diagnosis, prognosis, and potential therapeutic targets. Although down-regulation of lncRNA LET in several cancers has been studied, its role in gastric cancer remains unknown. The aim of our study was to investigate the expression, and clinical significance of lncRNA LET in gastric cancer. Methods: The expression of lncRNA LET was detected by quantitative real-time PCR (qRT-PCR) in pairs of tumor tissues and adjacent non-tumor tissues of 93 gastric cancer patients. Then, we analyzed the potential relationship between lncRNA LET expression levels in tumor tissues and clinicopathological features of gastric cancer, and clinical outcome. Results: We found that lncRNA LET expression was markedly down-regulated in tumor tissues compared with adjacent non-tumor tissues, and associated with depth of invasion, lymph node metastasis, distant metastasis, and TNM stage. Kaplan-Meier analysis showed that patients with low lncRNA LET expression had a poor overall survival than those with high lncRNA LET expression. Moreover, univariate and multivariate analyses showed that low lncRNA LET expression was an independent poor prognostic factor for gastric cancer patients. Conclusions: Our data provided the first evidence that lncRNA LET might be a novel prognostic indicator in gastric cancer and might be a potential target for diagnosis and gene therapy.     

Loss of ARID1A expression is associated with poor prognosis in non-small cell lung cancer

Adenine-thymine-rich inactive domain-containing protein 1A (ARID1A) is a large subunit of the switch-sucrose nonfermenting (SWI-SNF) complex. ARID1A is considered to be a tumor suppressor in various cancers. We investigated the clinicopathological significance including prognosis of ARID1A expression in non-small cell lung cancer (NSCLC). ARID1A expression was studied by tissue microarray immunohistochemical analysis of 171 surgically resected NSCLC specimens including adenocarcinoma (ADC) and squamous cell carcinoma (SCC) on tissue microarray. Semiquantitative immunohistochemical score was obtained by multiplying the intensity and percentage scores. The overall score was further simplified by dichotomizing into either negative (score < 4) or positive (score ≥ 4) for each patient. The ARID1A-negative group revealed significantly higher correlations with male sex (p = 0.020), larger tumor size (p = 0.007), SCC than with ADC (p = 0.023) and smoking (p = 0.001). Univariate survival analysis showed that the ARID1A-negative group had a significantly shorter cancer specific survival than the ARID1A-positive group (p = 0.018). Multivariate survival analysis showed that ARID1A negativity (p = 0.022) were independent prognostic factors related with shorter cancer specific survival for NSCLC. In conclusion, Loss of ARID1A expression is a potential molecular marker to predictive of poor prognosis of NSCLC.     

肿瘤转移相关蛋白1的表达与人直肠癌组织淋巴管转移及预后关系

目的观察肿瘤转移相关蛋白1(MTA1)与直肠癌淋巴结转移及预后的关系,探讨MTA1在直肠癌发生发展过程中的作用。方法应用免疫组化法和实时荧光定量PCR方法检测MTA1在45例人直肠癌和20例直肠息肉组织中的表达,并结合临床病理特征和生存资料进行相关分析。结果直肠癌组织中MTA1蛋白及mRNA的表达较直肠息肉组显著增加(P<0.05),MTA1表达与直肠癌淋巴结转移、Dukes临床分期密切相关(P<0.05)。MTA1阳性表达与生存率负相关(P<0.05)。结论 MTA1高表达促进直肠癌淋巴结转移,检测MTA1表达可成为直肠癌预后不良的重要指标。     

Elevated TRIM23 expression predicts poor prognosis in Chinese gastric cancer

The gene TRIM23 (tripartite motif containing 23) is a member of the tripartite motif (TRIM) family whose expression putatively participates in many pathophysiological processes. Nonetheless, the role of TRIM23 in gastric cancer (GC) remains uncertain. Our study evaluated the expression of TRIM23 in GC tissues and cell lines, and investigated an association between TRIM23 and survival. In the present study, our results demonstrated that TRIM23 mRNA and protein were frequently over-expressed in GC cell lines and GC tissues. High level of TRIM23 protein correlated with tumor size, tumor-node-metastasis (TNM) stage, depth of invasion, lymph node metastasis (LNM), tumor differentiation, and nerve invasion. Compared with the low TRIM23 protein group, the high TRIM23 protein group was significantly associated with worse prognosis of GC patients. Consistently, the KM-plot database suggested that high TRIM23 mRNA expression was also linked to a poor prognosis in GC patients both in positive and negative subgroups of human epidermal growth factor receptor 2 (HER2). But in the HER2 positive subgroup, the advantages of the low TRIM23 expression on overall survival were much more statistically significant. The univariate analysis indicated that TRIM23 expression correlated with overall survival. The multivariate analysis showed that independent factors of prognosis in GC were lymph node metastasis, vascular invasion, and depth of invasion. In summary, TRIM23 may be associated with progression of GC, and may be considered a therapeutic target for GC patients.     

High expression of integrin-linked kinase predicts aggressiveness and poor prognosis in patients with gastric cancer

Integrin-linked kinase (ILK), an intracellular serine/threonine protein kinase, has been reported to be highly expressed in many human malignancies, including gastric cancer. However, the prognostic significance of ILK expression in gastric cancer remains to be elucidated. In the present study, ILK expression in 95 gastric tumor tissues and 30 adjacent non-cancerous gastric mucosa was evaluated by immunohistochemistry and correlated with clinicopathological characteristics and patients’ outcome. The results showed that high ILK expression was observed in 47.4% (45/95) of gastric cancer tissues, but only in 20.0% (6/30) of adjacent gastric mucosa. Clinicopathological analysis indicated that high ILK expression was significantly associated with poor tumor differentiation (P = 0.024), advanced TNM stage (P = 0.006), tumor invasion (P = 0.001), and lymph node metastasis (P = 0.014). Kaplan–Meier survival curves demonstrated that patients with high ILK expression had substantially shorter overall survival that those with low ILK expression (P = 0.043, log-rank test). Furthermore, Cox multivariate regression analysis identified ILK expression as an independent prognostic factor for overall survival of gastric cancer patients (hazard ratio, 1.95; 95% confidence interval, 1.02–3.13; P = 0.026). In conclusion, our data suggest that ILK may contribute to the malignant progression of gastric cancer and serve as a novel prognostic indicator for gastric cancer patients.     

Foxp3~+ Tregs和PD1在胃癌组织中的表达及其临床病理意义

目的:探讨胃癌组织中Foxp3+调节性T细胞(Foxp3+Tregs)与程序性死亡受体1(PD1)的表达情况及两者与胃癌患者临床病理和预后的关系。方法:采用免疫组织化学方法检测111例胃癌患者癌组织和20例正常胃黏膜组织中Foxp3+Tregs及PD1的表达情况,分析胃癌组织中两者的表达与患者临床病理和预后的关系及两项指标之间的相关性。结果:胃癌组织中Foxp3+Tregs和PD1表达增加,PD1表达于肿瘤浸润性淋巴细胞(TILs),两者的表达均与淋巴结转移及TNM分期相关(P0.05),而与其它临床病理因素如肿瘤大小、病理类型,病变部位均无关,以上指标表达阳性者总体生存率低(P0.05),预后差。胃癌组织中Foxp3+Tregs与PD1+TILs的表达之间存在显著的正相关(P0.01)。结论:胃癌组织中存在Foxp3+Tregs和PD1+TILs共同表达,二者可作为判断胃癌患者疾病进展及预后的生物学标志物。     

Long non-coding RNA CCAT2 is up-regulated in gastric cancer and associated with poor prognosis

Introduction: Dysregulation of long non-coding RNAs (lncRNAs) play important roles in tumor progression. The aim of our study was to explore the clinicopathologic and prognostic significance of lncRNA CCAT2 expression in human gastric cancer. Methods: Expression levels of lncRNA CCAT2 in 85 pairs of gastric cancer and adjacent non-tumor tissues were detected by quantitative real-time PCR (qRT-PCR). In order to determine its prognostic value, overall survival and progression-free survival were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Results: Expression levels of lncRNA CCAT2 in gastric cancer tissues were significantly higher than those in adjacent non-tumor tissues. By statistical analyses, high lncRNA CCAT2 expression was observed to be closely correlated with higher incidence of lymph node metastasis and distance metastasis. Moreover, patients with high lncRNA CCAT2 expression had shorter overall survival and progression-free survival compared with the low lncRNA CCAT2 group. Multivariate analyses indicated that high lncRNA CCAT2 expression was an independent poor prognostic factor for gastric cancer patients. Conclusions: Our results suggested that up-regulation of lncRNA CCAT2 was correlated with gastric cancer progression, and lncRNA CCAT2 might be a potential molecular biomarker for predicting the prognosis of patients.     

Obesity is associated with a poorer prognosis in women with hormone receptor positive breast cancer

Objective

Whether moderate to severe obesity (body mass index (BMI) ≥ 30 to <40 kg/m²) contributes to breast cancer recurrence and mortality remains uncertain.

Subjects and methods

1199 women, recruited within 12 months of their diagnosis of hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2−) invasive breast cancer completed an enrolment questionnaire and an annual follow-up questionnaire every 12 months for another 5 years. The impact of obesity on time to either local or distant recurrence or new breast cancer, or death due to breast cancer was determined by Cox regression. Women in the most extreme categories of BMI (<18.5 and ≥40) were excluded from the analysis.

Results

Of the 1155 included women, mean age, 58.4 ± 11.6 years, 53.8% had Stage 1 disease and 88.9% received oral adjuvant endocrine therapy (OAET) within 2 years of diagnosis. The likelihood of an event was significantly associated with moderate to severe obesity (HR = 1.71, 95%CI, 1.12–2.62, p = 0.014), disease beyond Stage 1 (HR = 2.87, 95% CI 1.73–4.75, p < 0.001), OAET (HR = 0.26, 95%CI 0.14–0.46, p < 0.001), mastectomy (HR = 3.28, 95%CI 1.98–5.44, p < 0.001) and radiotherapy (HR = 2.12, 95%CI 1.24–3.63, p = 0.006). For Stage 1 disease, only moderate to severe obesity (HR 3.23, 95%CI 1.48–7.03, p = 0.003) and OAET use (HR 0.41, 95%CI 0.17–0.98, p = 0.046) were significantly associated with an event.

Conclusion

Moderate to severe obesity is associated with a poorer invasive breast cancer prognosis; this is also true for women with Stage 1 disease, and is independent of age and treatment.     

Caveolin-1 immuno-expression in human gastric cancer: histopathogenetic hypotheses

The immunohistochemical expression of caveolin-1 (cav-1) was evaluated in a series of gastric carcinomas (GC) and in the adjacent normal gastric mucosa. Cav-1 immuno-expression was found in most GC (94%) with a significantly higher amount in the Lauren intestinal type in comparison to the diffuse-type carcinomas. Interestingly, gastric intestinal metaplasia as well as the cells at the base and neck of gastric pits within all fundic mucosal fragments showed an evident cav-1 immuno-staining, suggesting a histogenetic derivation of these lesions from the trans-differentiation of chief cells or from a cryptic progenitor population at the base of fundic glands, as recently hypothesized by other authors. The absence of significant correlations between cav-1 immuno-expression and the other clinico-pathological parameters, such as the stage of disease or the patients overall survival, indicates that the role of cav-1 in GC is neither stage-specific nor related to prognosis.