Overexpression of stathmin plays a pivotal role in the metastasis of esophageal squamous cell carcinoma.

PURPOSE: Esophageal squamous cell carcinoma (ESCC) is a serious malignant tumor that affects human health. We analyzed the correlation between serum stathmin level and ESCC and elucidated the molecular mechanisms of stathmin's promotion of ESCC cell invasion and metastasis. METHODS: Stathmin level in ESCC and healthy control serum were detected by enzyme-linked immunosorbent assay (ELISA), and the clinical parameters were analyzed. We established ESCC cells with stathmin overexpression or knockdown and then evaluated the effects of stathmin on invasion and metastasis in ESCC. Differentially expressed genes were analyzed by Human Transcriptome Array and confirmed by RT-PCR. The expression levels of the integrin family, focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK) were detected by immunoblotting. RESULTS: Serum levels of stathmin were significantly higher in ESCC than in control serum and associated with lymph node metastasis, tumor stage and size. Furthermore, we found that stathmin promoted migration and invasion of ESCC cells in vitro and in vivo. In addition, we confirmed that the activation of the integrinα5ß1/FAK/ERK pathway is increased in stathmin-overexpression cells and accelerates cell motility by enhancing cell adhesion ability. CONCLUSION: Stathmin may predict a potential metastasis biomarker for ESCC.

Episomal lentiviral vectors confer erythropoietin expression in dividing cells.

Lentiviral vectors are now widely considered as one of the most common gene delivery tools for dividing and non-dividing cells. However, insertional mutagenesis has been found in clinical trials with retroviral vectors, which poses a safety risk. The use of non-integrating lentiviral (NIL) vectors, which avoid integration, eliminates the insertional mutagenesis problem. These NIL vectors are unable to mediate stable gene delivery into dividing cells, which makes them of limited use in the clinical practice of gene therapy. In this study, we constructed a NIL vector which harbors the scaffold/matrix attachment region (S/MAR) sequence and a therapeutic gene. NIL retained episomal erythropoietin (EPO) gene expression for 74days in dividing cells both with and without selection. Furthermore, Southern blot analysis showed that the NIL vector was retained extrachromosomally in CHO cells. In conclusion, the NIL vector based on an S/MAR sequence retained the extrachromosomal expression of a therapeutic gene in dividing cells. Our results show that NIL vectors maybe a safe and effective means of gene delivery, which is of potential clinical significance.

Plasma D-dimer value as a predictor of malignant lymph node involvement in operable non-small cell lung cancer.

Fibrin deposition and remodelling of the extracellular matrix are important early steps in tumour metastasis. The D-dimer value is an indicator of intravascular fibrin formation and degradation. Thus, the D-dimer value may be a predictor of the malignant involvement of lymph nodes in operable non-small cell lung cancer (NSCLC) patients. The study comprised 142 highly suspected lung cancer patients scheduled to undergo pneumonectomy, lobectomy or wedge resection. Of the 142 patients, 124 were subsequently diagnosed as NSCLC, and 18 were subsequently diagnosed as benign lung disease by histological examination. Preoperative plasma D-dimer values were quantified, and the relationship between plasma D-dimer and clinical variables including tumour size, involvement of lymph nodes and clinical stage was examined using Spearman correlation coefficients and χ (2) tests. The median plasma D-dimer values were statistically higher in NSCLC patients with malignant lymph nodes than in those who suffered either benign lung disease or carcinoma in situ (Kruskal-Wallis test; P = 0.001). Plasma D-dimer values were significantly correlated with clinical stage (ANOVA; P = 0.009). An obvious relationship was observed between elevated D-dimer (>0.475 mg/L fibrinogen equivalent units) and malignant lymph node involvement (χ (2) test; P = 0.0000). This correlation suggests that the plasma D-dimer value is a clinically important predictor for the malignant involvement of lymph nodes in operable NSCLC.

Postoperative dynamic changes in the concentration of CK19-2G2 in lung cancer patients and the clinical value of this marker.

CK19-2G2, a newly identified fragment of cytokeratin 19, is a candidate marker for the diagnosis of lung cancer and for monitoring a patient's response to lung cancer treatment. This study investigated the postoperative dynamic changes in serum CK19-2G2 concentration and the clinical value of this marker in lung cancer patients. Preoperative and postoperative concentrations of CK19-2G2 were measured in 352 lung cancer patients who had undergone pulmonary resection. Stratified analyses based on pathologic types and lymph node involvement were performed to determine their possible impacts on postoperative CK19-2G2 concentration. CK19-2G2 concentration was significantly lower after tumor resection than before tumor resection. For squamous cell carcinoma patients, the postoperative CK19-2G2 concentration had decreased significantly at 1 week after surgery and had decreased further at 1 month after surgery. For adenocarcinoma patients, there were little changes in the CK19-2G2 concentration during 1 week to 1 month after surgery. At 1 week after surgery, the CK19-2G2 concentration was slightly higher in patients with N2 stage disease than in those with N0 and N1 stage disease, and this difference increased at 1 month after surgery. Postoperative CK19-2G2 concentration may be an indicator of prognosis. An increase after the initial drop in CK19-2G2 concentration after surgery may indicate a poor prognosis.

Polymorphisms in UGT2B4 and susceptibility to pancreatic cancer.

As an important enzyme in the conjugation phase of drug clearance, UGT2B4 helps metabolize various endogenous and exogenous substances, and polymorphisms in the corresponding gene can influence enzyme activity. This study investigated the association between polymorphisms in UGT2B4 and the risk of developing pancreatic cancer in Han Chinese individuals. A hospital-based case-control study was conducted with 1579 healthy controls and 406 pancreatic cancer patients from China. Genomic DNA was obtained from peripheral blood lymphocytes. Time-of-flight mass spectrometry was used to genotype polymorphic loci in UGT2B4, and the association between these polymorphisms and susceptibility to pancreatic cancer was expressed as odds ratios (ORs) with 95% confidence intervals (CIs), as calculated using multivariable logistic regression analysis. The rs1131878C > T polymorphism (NT_016354.20: g.10558805C > T) in UGT2B4 was associated with an increased pancreatic cancer risk. Compared to the C/C genotype, the C/T genotype conferred 1.39 times higher the pancreatic cancer risk (95% CI = 1.09-1.77; P = 0.007), and the T/T genotype conferred 2.97 times higher the pancreatic cancer risk (95% CI = 1.24-7.08; P = 0.014). In contrast, compared with the A/A genotype, the A/C genotype at the rs3822179 locus in UGT2B4 (NT_016354.20: g.10569096C > A) bestowed a 20% risk reduction (OR = 0.80, 95% CI = 0.67-0.95; P = 0.011). However, the risk was not significantly reduced with the C/C genotype (OR = 0.77, 95% CI = 0.52-1.14, P = 0.191). Polymorphisms in UGT2B4 affect the risk of pancreatic cancer occurrence in Han Chinese individuals.

Association of Genetic Polymorphisms in UDP-Glucuronosyltransferases 2B17 with the Risk of Pancreatic Cancer in Chinese Han Population.

BACKGROUND: This study is aimed to investigate the association between polymorphisms in UGT2B17 and the risk of developing pancreatic cancer in Chinese Han population. METHODS: A hospital-based case-control study was conducted, and 1579 healthy controls and 406 pancreatic cancer patients were enrolled. Real-time PCR was applied to identify the genetic polymorphisms in the subjects, and multivariable logistic regression analysis was performed to investigate the association between UGT2B17 polymorphisms and susceptibility to pancreatic cancer. RESULTS: The prevalence of the UGT2B17 del/del, del/ins, and ins/ins in cases were 72.9%, 24.0%, and 3.1%, respectively, and in controls 66.6%, 30.7%, and 2.7%, respectively. Multivariable logistic regression revealed that, compared with the del/del genotype, the del/ins genotype in UGT2B17 is related to a significant reduction in pancreatic cancer risk (OR = 0.77, 95% CI = 0.60 - 0.99; P = 0.04). In the female subjects, compared with the del/del genotype, the del/ins genotype was related to a substantial reduction in pancreatic cancer risk (OR = 0.59, 95% CI = 0.39 - 0.90, P = 0.01). CONCLUSIONS: All these results indicate a higher ratio of UGT2B17 deletion polymorphisms in Asians. UGT2B17 deletion polymorphisms are associated with the risk of developing pancreatic cancer in Chinese Han population, especially in the female population.

Serum cytokeratin 19 fragment, CK19-2G2, as a newly identified biomarker for lung cancer.

BACKGROUND: CK19-2G2, a new fragment of cytokeratin 19, is a potential tumor marker for diagnosing lung cancer. The preoperative level of serum CK19-2G2 has been demonstrated to be associated with tumor metastasis and survival of breast cancer patients. This study investigated the postoperative dynamic changes in serum CK19-2G2 levels and its clinical significance in lung cancer patients. MATERIALS AND METHODS: Preoperative serum CK19-2G2 levels were measured in 630 lung cancer patients and were compared with individuals with benign pulmonary diseases (n = 134) and healthy volunteers (n = 263). In 352 cases, the patients underwent surgery. In these patients, in addition to preoperative assays, serum CK19-2G2 was also monitored at 1 week and 1 month after the operation. RESULTS: The preoperative baseline levels of serum CK19-2G2 was significantly higher in lung cancer patients than patients with benign diseases and healthy controls (P<0.001). The postoperative levels of CK19-2G2 declined significantly within 1 week after tumor resection. Hereafter, a further decrease was observed in the patients who underwent palliative operations, while for the patients in the radical resection group, their CK19-2G2 levels stabilized. CONCLUSION: CK19-2G2 may be a candidate marker for diagnosing and monitoring a patient's response to lung cancer treatment. In addition, CK19-2G2 may be an indicator for micrometastases in lung cancer patients.

Diagnostic accuracy of serum HE4, CA125 and ROMA in patients with ovarian cancer: a meta-analysis.

CA125, human epididymis secretary protein 4 (HE4) and the Risk of Ovarian Malignancy Algorithm (ROMA) could be used for diagnosing ovarian cancer (OCa). However, it has not been conclusively determined which of these markers yields the best diagnostic accuracy. Therefore, we conducted a meta-analysis to evaluate the diagnostic value of these markers. We systematically searched the PubMed and ScienceDirect databases and identified 32 studies that evaluated the role of CA125, HE4 and ROMA in diagnosing OCa. The bivariate random-effects approach was used to calculate the pooled estimates by considering the heterogeneity of major related parameters such as the menopausal status, International Federation of Gynecology and Obstetrics stages, detection method and blinded design. Three tests yielded similar discriminatory performances in the OCa diagnosis (AUC [95 % CI]-0.89 [0.86-0.92] for HE4; 0.87 [0.84-0.90] for CA125; 0.91 [0.88-0.93] for ROMA). HE4 yielded a higher specificity than CA125 and ROMA (HE4 93.60 [90.00-95.90] >CA125 82.10 [76.60-86.50] and ROMA 82.40 [77.40-86.50]), especially in the premenopausal subgroup (HE4 93.80 [88.40-96.80] >CA125 76.30 [63.30-85.70] and ROMA 85.10 [80.40-88.80]). In contrast, CA125 and ROMA performed significantly better in the postmenopausal subgroup than in the premenopausal subgroup (AUC [95 % CI]-CA125-premenopausal 0.85 [0.82-0.88]

CAG repeats in the androgen receptor gene are shorter in patients with pulmonary, esophageal or bladder carcinoma and longer in women with uterine leiomyoma.

Preferential occurrence of pulmonary, esophageal and bladder carcinomas in males indicate a possible involvement of androgen receptor (AR)-mediated functions. We evaluated the roles of the CAG repeat polymorphism in AR exon 1 in development of these lesions. The exon 1 of AR gene was amplified in samples from 198 male patients with lung carcinoma, 183 with esophageal carcinoma, 95 with bladder carcinoma and 94 males with appendicitis, as a reference group. Mean numbers of the CAG repeat in these 3 cancer groups were determined to be 20.2, 20.0 and 20.0, respectively, all being significantly smaller than that of the reference group (21.1; P<0.05). Samples from 118 female patients with lung carcinoma and 154 females with appendicitis, as a reference group, were examined, with the mean CAG repeat number significantly smaller (19.8) than that of the female reference group (20.7; P<0.01). Samples from 108 patients with uterine leiomyoma were also examined, and their CAG repeat numbers were found to be markedly expanded (23.4; P<0.01). The patients with multiple leiomyomas tend to carry a longer CAG repeat structure, with the mean CAG repeat number longer in the multicentric multiple cases (24.1) compared to that of the unicentric, multinodular cases (22.2) and those with solitary lesions (23.1; P<0.01). These results indicate that a shorter CAG repeat structure may predispose individuals to a higher risk to some male-predominant neoplasms including pulmonary, esophageal and bladder carcinomas and a longer one confers women greater susceptibility to leiomyoma development in the uterus.