长链非编码RNA CYTOR在人类癌症中调控机制研究进展

癌症因其多具有异质性、耐药性以及易复发转移的特点,临床很难治愈。揭示癌症发生发展的分子机制、鉴定新的诊断标志物和分子治疗靶标,无疑是解决癌症早期诊断、治疗以及改善患者预后问题的有效策略。越来越多的研究表明,长链非编码RNA(long non-coding RNA,lncRNA)在人类癌症中特异性表达,是癌症发生发展的关键调节因子。细胞骨架调节因子RNA(cytoskeleton regulator RNA,CYTOR)是近年发现的一种致癌性lncRNA。CYTOR在多种类型癌症中均高表达,通过多种途径调控癌症发生发展,可能是癌症早期诊断、分子靶向治疗以及评估预后有效生物标志物。该文综述了CYTOR在人类癌症中的分子调控机制及其相关生物学效应,以期为临床癌症的诊疗提供新的科学参考。

Biomarkers and potential pathogenesis of colorectal cancer-related ischemic stroke

AIM To investigate the specific biomarkers and potential pathogenesis of colorectal cancer-related ischemic stroke(CRCIS).METHODS A retrospective study was conducted on CRCIS patients(colorectal cancer patients with ischemic stroke without conventional stroke risk factors) registered at seven centers between January 2007 and December 2017. Clinical data and laboratory and imaging findings were compared with age-and sex-matched patients with colorectal cancer(CRC) without ischemic stroke that were admitted to the same hospital during the same period. Univariate and multivariate analyses were performed to analyze the independent risk factors for CRCIS. A receiver operator characteristic curve was configured to calculate the optimal cut-off value of the products of the independent risk factors for CRCIS. RESULTS A total of 114 CRCIS patients and 114 CRC patients were included. Multiple lesions in multiple vascular territories were common in CRCIS patients(71, 62.28%). The levels of plasma D-dimer, carcinoembryonic antigen(CEA), cancer antigen 125, and neutrophil count were significantly higher in CRCIS patients than in CRC patients. Multiple logistic regression analysis revealed that plasma D-dimer levels [odds ratio(OR) = 1.002, 95% confidence interval(CI): 1.001-1.003, P < 0.001], CEA levels(OR = 1.011, 95%CI: 1.006-1.015, P < 0.001), and neutrophil count levels(OR = 1.626, 95%CI: 1.268-2.087, P < 0.001) were independent risk factors for CRCIS. In addition, receiver operator characteristic curve revealed that the area under curve for the products of plasma D-dimer, CEA, and neutrophil count was 0.889 ± 0.022(95%CI: 0.847-0.932, P < 0.001), and the optimal cut-off value for the product was 252.06, which was called the CRCIS Index, with a sensitivity of 86.0% and specificity of 79.8%.CONCLUSION Hypercoagulability induced by elevated CEA and neutrophils may be an important cause of CRCIS. The CRCIS index, which serves as a biomarker of CRCIS, needs further study.

Clinicopathological and prognostic significance of aberrant Arpin expression in gastric cancer

AIM To detect the expression of Arpin, and determine its correlation with clinicopathological characteristics and the prognosis of gastric cancer (GC) patients. METHODS A total of 176 GC patients were enrolled as study subjects and classified into groups according to different clinicopathological variables. GC mucosal tissues were obtained via surgery. Another 43 paraffin-embedded tissue blocks of normal gastric epithelium (> 5 cm away from the edge of the tumor) were included in the control group. Immunohistochemistry (IHC) for the Arpin and Arp3 proteins was performed on the formalin-fixed, paraffin-embedded GC tissues. Additionally, expression of the Arpin protein in 43 normal gastric tissues was also determined using IHC. RESULTS Expression of the Arpin protein in GC was lower than that in normal gastric mucosa (30.68% vs 60.47%, P < 0.001). A chi(2) test of the 176 GC samples used for IHC showed that decreased Arpin expression was associated with advanced TNM stage (P < 0.01) and the presence or absence of lymph node metastasis (80.92% vs 35.56%, P < 0.001). Additionally, a significant correlation was observed between the expression of Arpin and the presence of the Arp2/3 complex in GC tissues (chi(2) = 30.535, P < 0.001). Moreover, a multivariate Cox regression analysis revealed that Arpin expression [hazard ratio (HR) = 0.551, P = 0.029] and TNM stage (HR = 5.344, P = 0.001) were independent prognostic markers for overall survival of GC patients. Regarding the 3-year disease-free survival (DFS), the recurrence rate of GC patients with low Arpin expression levels (median DFS 19 mo) was higher than that in the high-Arpin-expression group (median DFS 34 mo, P = 0.022). CONCLUSION Low Arpin levels are associated with clinicopathological variables and a poor prognosis in GC patients. Arpin may be regarded as a potential prognostic indicator in GC.

Family history of cancer in Chinese gastric cancer patients

Objective:The aim of the study was to investigate the influence of gastric cancer family history in the gastric cancer (GC) patients. Methods: Gastric cancer family histories within second degree relatives and clinicopathological features were obtained for 497 patients. Results:Of the 497 probands,235 probands were incorporated into familial gastric cancer (FGC) group (there were at least two GC members in the family); 262 probands were included in the non-FGC group (relatives only affected with non-GCs). Of 614 tumors in relatives,GC was the most frequent,followed by lung cancer,esophageal cancer,hepatocellular cancer,colorectal cancer,urogenital cancer,breast cancer,and pancreatic cancer. Most affected members aggregated within first-degree relatives. The ratio of males to females in affected first-degree relatives was usually higher in male probands. Paternal history of GC was a strong risk for GC in males,while risk of GC by maternal history of GCs was increased in females. Difference in tumor histological types between the two groups was derived from an excess of diffuse GC in non-FGC male probands. The lower site was the most frequent tumor location in all subgroups. Conclusion:Distribution of associated non-GCs in a family history of GC may vary with geographic areas. GC may have different genetic and/or environmental etiology in different families,and a certain subtype may be inherited in a male-influenced fashion.

Dual-specificity phosphatase 6(DUSP6): a review of its molecular characteristics and clinical relevance in cancer

Mitogen-activated protein kinases(MAPKs) are the main regulators of cellular proliferation, growth, and survival in physiological or pathological conditions. Aberrant MAPK signaling plays a pivotal role in carcinogenesis, which leads to development and progression of human cancer. Dual-specificity phosphatase 6(DUSP6), a member of the MAPK phosphatase family, interacts with specifically targeted extracellular signal-regulated kinase 1/2 via negative feedback regulation in the MAPK pathway of mammalian cells. This phosphatase functions in a dual manner, pro-oncogenic or tumor-suppressive, depending on the type of cancer. To date, the tumor-suppressive role of DUSP6 has been demonstrated in pancreatic cancer, non-small cell lung cancer, esophageal squamous cell and nasopharyngeal carcinoma, and ovarian cancer. Its pro-oncogenic role has been observed in human glioblastoma, thyroid carcinoma, breast cancer, and acute myeloid carcinoma. Both roles of DUSP6 have been documented in malignant melanoma depending on the histological subtype of the cancer. Loss-or gain-of-function effects of DUSP6 in these cancers highlights the significance of this phosphatase in carcinogenesis. Development of methods that use the DUSP6 gene as a therapeutic target for cancer treatment or as a prognostic factor for diagnosis and evaluation of cancer treatment outcome has great potential. This review focuses on molecular characteristics of the DUSP6 gene and its role in cancers in the purview of development, progression, and cancer treatment outcome.

Age distribution,polyps and rectal cancer in the Egyptian population-based cancer registry

AIM:To describe the clinical and epidemiologic profiles of the disease and to compare the findings with those generated from the previous hospital-based studies.METHODS:The Gharbiah cancer registry is the only population-based cancer registry in Egypt since 1998.We analyzed the data of all colorectal cancer patients included in the registry for the period of 1999-2007.All medical records of the 1364 patients diagnosed in Gharbiah during the study period were retrieved and the following information abstracted:age,residence,diagnosis date,grade,stage,topology,clinical characteristics,and histology variables.Egyptian census data for 1996 and 2006 were used to provide the general population's statistics on age,sex,residence and other related demographic factors.In addition to age-and sex-specific incidence rate analyses,we analyze the data to explore the incidence distribution by rural-urban differences among the 8 districts of the province.We also compared the incidence rates of Gharbiah to the rates of the Surveillance Epidemiology and End Results(SEER) data of the United States.RESULTS:Over the 9 year-period,1364 colorectal cancer cases were included.The disease incidence under age 40 years was relatively high(1.3/10 5) while the incidence in the age groups 40 and over was very low(12.0/10 5,19.4/10 5 and 21.2/10 5 in the age groups 40-59 years,60-69 years and > 70 years,respectively).The vast majority of tumors(97.2%) had no polyps and 37.2% of the patients presented with primary lesions in the rectum.Colorectal cancer was more common in patients from urban(55%) than rural(45%) areas.Regional differences in colon and rectal cancer incidence in the 8 districts of the study province may reflect different etiologic patterns in this population.The registry data of Egypt shows a slightly higher incidence of colorectal cancer than the United States in subjects under age 40 years.The results also shows significantly lower incidence of colorectal cancer in subjects over age 40 years compared to the same age group in the United States SEER.CONCLUSION:Low rate of polyps,low incidence in older subjects,and high rate of rectal cancer in Egypt.Future studies should explore clinical and molecular disease patterns.

A data-mining approach to biomarker identification from protein profiles using discrete stationary wavelet transform

Objective: To develop a new bioinformatic tool based on a data-mining approach for extraction of the most infor- mative proteins that could be used to find the potential biomarkers for the detection of cancer. Methods: Two independent datasets from serum samples of 253 ovarian cancer and 167 breast cancer patients were used. The samples were examined by surface- enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). The datasets were used to extract the informative proteins using a data-mining method in the discrete stationary wavelet transform domain. As a dimensionality re- duction procedure, the hard thresholding method was applied to reduce the number of wavelet coefficients. Also, a distance measure was used to select the most discriminative coefficients. To find the potential biomarkers using the selected wavelet coefficients, we applied the inverse discrete stationary wavelet transform combined with a two-sided t-test. Results: From the ovarian cancer dataset, a set of five proteins were detected as potential biomarkers that could be used to identify the cancer patients from the healthy cases with accuracy, sensitivity, and specificity of 100%. Also, from the breast cancer dataset, a set of eight proteins were found as the potential biomarkers that could separate the healthy cases from the cancer patients with accuracy of 98.26%, sensitivity of 100%, and specificity of 95.6%. Conclusion: The results have shown that the new bioinformatic tool can be used in combination with the high-throughput proteomic data such as SELDI-TOF MS to find the potential biomarkers with high discriminative power.

Prognostic factors of gastric cancer tumours of less than 2 cm in diameter

Objective:The aim of our study was to identify clinicopathological characteristics as predictive factors for gastric cancer tumours of less than 2 cm in diameter.Methods:The clinicopathological features of 129 patients with gastric cancer tumour of less than 2 cm in diameter were reviewed retrospectively from hospital records between 1980 and 2000.The results of retrospective analysis of clinicopathological data of 58 patients with advanced cancer were compared with those of 71 patients with early cancer.Univariate and multivariate analyses of patients with gastric cancer tumours were performed to evaluate the prognostic significance of clinicopathological features.Results:Lymph-node metastasis was found more frequently in the advanced cancer group than in the early cancer group.In univariate analysis,unfavorable prognostic factors included deep cancer invasion.Using Cox's proportional hazard regression model,only depth of invasion emerged as an independent statistically significant prognostic parameter associated with long-term survival.Conclusion:Depth of invasion is an independent prognostic factor for gastric cancer tumours of less than 2 cm in diameter.Laparoscopic surgery should not be performed on tumours that are diagnosis in advanced stage and lymph-node involvement.We recommend laparoscopic surgery involving local resection of the stomach without lymphadenectomy for small,early gastric cancer tumours.However,the validity of this recommendation should be tested by a prospective randomized control trial in the future.

Predictive factors of lymph node metastasis in intramucosal poorly differentiated early gastric cancer and their impact on the laparoscopic surgery

Objective The aim of this study was to identify clinicopathological factors predictive of lymph node metastasis (LNM) in intramucosal poorly differentiated early gastric cancer (EGC), and further to expand the possibility of using laparoscopic surgery for the treatment of intramucosal poorly differentiated EGC.

解读癌症研究的里程碑:Hallmarks of Cancer

征服癌症是人类永恒的话题。20世纪后半叶,肿瘤研究开始进入分子时代,癌症复杂多样的表型、机制及治疗反应逐渐被认识。2000年,一篇开创性综述“Hallmarks of Cancer”问世,更新至今,已总结出了癌症的14个特征,将肿瘤研究中日益繁杂的概念提炼成一门逻辑科学,有助于更全面地理解癌症发生、发展机制并将这些知识应用于肿瘤的诊断和治疗中,掌握、应用以及继续探索癌症的特征必将有助于在未来更加自信地面对肿瘤疾病带来的挑战。