Overexpression of Periostin in Tumor Biopsy Samples Is Associated With Prostate Cancer Phenotype and Clinical Outcome

Background

Overexpression of periostin (POSTN) is associated with prostate cancer (PCa) aggressiveness. We investigated the prognostic significance of POSTN expression in tumor biopsy samples of patients with PCa.

The Presence of EpCAM-/CD49f+ Cells in Breast Cancer Is Associated with a Poor Clinical Outcome

Purpose

It is well established that breast cancer stem cells (BCSCs) play an essential role in tumor invasion for both local and distant metastasis. The aim of this study was to establish whether BCSCs could act as a prognostic and clinical marker.

Methods

We analyzed tumor tissues from 161 breast cancer patients. Dual immunohistochemistry and immunofluorescence were performed on all the slides, and we analyzed the relationship between EpCAM^-/CD49f⁺ tumor cells and key clinical and prognostic factors.

Results

Univariate survival analysis using the Kaplan-Meier method showed that the presence of EpCAM^-/CD49f⁺ tumor cells in breast cancer was significantly associated with shorter disease-free survival (DFS) and overall survival (OS). Multivariate analysis showed that the presence of EpCAM^-/CD49f⁺ cells was associated with shorter DFS (p=0.010; hazard ratio [HR], 2.070) and OS (p=0.002; HR, 3.235). Tumors containing EpCAM^-/CD49f⁺ cells were also more likely to metastasize after initial surgery (p=0.048).

Conclusion

Our study suggests that breast tumors containing EpCAM^-/CD49f⁺ cells are more likely to undergo distant metastasis after initial surgery and are associated with a shorter DFS and OS.     

Aurora-A Expression Is Independently Associated with Chromosomal Instability in Colorectal Cancer

AURKA (the official symbol for Aurora-A, STK15, or BTAK) regulates the function of centrosomes, spindles, and kinetochores for proper mitotic progression. AURKA overexpression is observed in various cancers including colon cancer, and a link between AURKA and chromosomal instability (CIN) has been proposed. However, no study has comprehensively examined AURKA expression in relation to CIN or prognosis using a large number of tumors. Using 517 colorectal cancers in two prospective cohort studies, we detected AURKA overexpression (by immunohistochemistry) in 98 tumors (19%). We assessed other molecular events including loss of heterozygosity (LOH) in 2p, 5q, 17q, and 18q, the CpG island methylation phenotype (CIMP), and microsatellite instability (MSI). Prognostic significance of AURKA was evaluated by Cox regression and Kaplan-Meier method. In both univariate and multivariate logistic regressions, AURKA overexpression was significantly associated with CIN (defined as the presence of LOH in any of the chromosomal segments; multivariate odds ratio, 2.97; 95% confidence interval, 1.40–6.29; P = .0045). In multivariate analysis, AURKA was associated with cyclin D1 expression (P = .010) and inversely with PIK3CA mutation (P=.014), fatty acid synthase expression (P=.028), and family history of colorectal cancer (P = .050), but not with sex, age, body mass index, tumor location, stage, CIMP, MSI, KRAS, BRAF, BMI, LINE-1 hypomethylation, p53, p21, β-catenin, or cyclooxygenase 2. AURKA was not significantly associated with clinical outcome or survival. In conclusion, AURKA overexpression is independently associated with CIN in colorectal cancer, supporting a potential role of Aurora kinase-A in colorectal carcinogenesis through genomic instability (rather than epigenomic instability).     

DNA Repair Gene Associated with Clinical Outcome ofEpithelial Ovarian Cancer Treated with Platinum-basedChemotherapy

Objective: The nucleotide excision repair (NER) and base excision repair (BER) pathways, two DNA repairpathways, are related to platinum resistance in cancer treatment. In this paper, we studied the association betweensingle nucleotide polymorphisms (SNPs) of involved genes and response to platinum-based chemotherapy inepithelial ovarian cancer. Method: Eight SNPs in XRCC1 (BER), XPC and XPD (NER) were assessed in 213patients with epithelial ovarian cancer using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR) techniques.Results: The median progression-free survival (PFS) of patients carrying the Lys/Lys and Lys/Gln+Gln/Glngenotype of the XPC Lys/Gln polymorphism were 25 and 12 months, respectively (P=0.039); and the mean overallsurvival (OS) of patients was 31.1 and 27.8 months, respectively (P=0.048). Cox’s multivariate analysis suggestedthat patients with epithelial ovarian cancer with the Gln allele had an increased risk of death (HR=1.75; 95%CI=1.06-2.91) compared to those with the Lys/Lys genotype. There are no associations between the XPC PAT+/-,XRCC1 Arg194Trp, Arg280His, Arg399Gln, and XPD Asp312Asn, Lys751Gln polymorphisms and the survivalof patients with epithelial ovarian cancer when treated with platinum-based chemotherapy. Conclusion: Ourresults indicated that the XPC Lys939Gln polymorphism may correlate with clinical outcome of patients withepithelial ovarian cancer when treated with platinum-based chemotherapy in Northern China.     

Consolidative Radiotherapy to Residual Masses After Chemotherapy Is Associated With Improved Outcome in Diffuse Large B-Cell Lymphoma. A Retrospective,Population-Based Study

Background

The role of consolidative radiotherapy (RT) in advanced diffuse large B-cell lymphoma (DLBCL) is not established.

The Functional Polymorphism of Erythropoietin Gene rs1617640 G>T Is Not Associated with Susceptibility and Clinical Outcome of Early-stage Breast Cancer

Recent data suggest that erythropoietin (EPO) plays a substantial role in cancer development and clinical outcome by stimulating cell proliferation, invasion and angiogenesis. A functional polymorphism (rs1617640 G>T) in the promoter region of the EPO gene increases EPO protein expression. In the present study, we investigated the association of EPO rs1617640 G>T with susceptibility and clinical outcome of early-stage breast cancer. Genomic DNA of 539 female patients with histologically confirmed early-stage breast cancer and 804 controls was genotyped for EPO rs1617640 G>T. No association was found between EPO rs1617640 G>T and early-stage breast cancer susceptibility and clinical outcome (hazard ratio=1.24, 95% confidence interval=1.82-1.90, p=0.31). In conclusion, our findings suggest a lack of influence of EPO rs1617640 G>T on early-stage breast carcinogenesis and clinical outcome.     

Elevated Serum Haptoglobin is Associated with Clinical Outcome in Triple-Negative Breast Cancer Patients

Background: Breast cancer is the most common malignancy with the highest incidence rates among womenworldwide. Triple-negative breast cancer (TNBC) disease is diagnosed more frequently in younger women, andis associated with a poor prognosis. Elevated levels of serum haptoglobin protein (Hp) are observed in manymalignant diseases including breast cancer. We evaluated the expression and prognostic value of Hp amongpatients with TNBC. Materials and Methods: Serum Hp levels were determined by Elisa in 41 patients withTNBC and 10 normal individuals. Hp status was correlated with other clinico-pathological parameters includingpatient survival. Results: Of the 41 patients with TNBC, Hp over expression was detected in 24 (59%) by Elisa.Hp up-regulation was confirmed by Elisa based quantification in the serum of 41 TNBC patients against lowergrades and 10 normal individuals. Survival analysis revealed that Hp (p=2.016x10-5), stage (p=2.166x10-5), distantmetastasis (p=2.217x10-5), tumor size (p=1.053x10-5), and tumor grade (p=0.001), correlated with patient survivalon univariate analysis. Multivariate analysis revealed that Hp (p=0.001), and grade of the disease (p=0.008)were independent predictors of survival. Conclusion: Our results indicate that serum levels of Hp may play arole as a potential serum biomarker and prognostic indicator among TNBC patients. Thus, Hp may presenta new promising prognostic biomarker in TNBC patients, but independent validations are now necessary forconfirmation.     

ITGAV在非小细胞肺癌中的表达及其与放射抵抗的关系

目的 探讨ITGAV的表达与NSCLC细胞放射敏感度的关系。方法 使用生物信息学方法分析ITGAV在NSCLC组织中的表达水平及其与NSCLC患者预后的相关性。克隆形成实验验证放射抵抗细胞与亲本细胞的放射敏感度差异,Western blot检测ITGAV的表达。Western blot、qRT-PCR验证si-ITGAV转染效率,选用最佳ITGAV干扰序列转染A549R、H1299R细胞。克隆形成实验、流式细胞术检测ITGAV干扰后对细胞克隆形成、凋亡和周期情况的影响。结果 ITGAV在非小细胞肺癌组织中表达水平明显高于正常组织（P<0.05）,且其高表达与患者不良预后有关。ITGAV干扰组细胞在4、6、8 Gy射线照射克隆形成能力与阴性对照组相比显著降低（均P<0.05）。经6 Gy照射后,ITGAV干扰组细胞的凋亡率增加（PH1299R<0.0001, PA549R=0.0002）,G2/M期细胞比例明显高于阴性对照组（PH1299R<0.0001, PA549R=0.0007）。结论 干扰ITGAV表达可以增加非小细胞肺癌放射敏感度。     

Reduced Expression of nm23 Is Associated with Metastasis of Human Gastric Carcinomas

Reduced expression of nm23 gene is implicated in high metastatic potential In a variety of malignancies. To elucidate the role of nm23 in human gastric carcinomas, we examined loss of heterozygosity (LOH) of nm23 gene by Southern blotting, nm23 mRNA expression by Northern blotting and nm23 protein expression by Western blotting as well as immunohistochemistry in both primary and metastatic tumors. LOH of nm23 gene was found in 2 (8%) out of the 23 informative gastric carcinomas. Twenty-two (84%) out of the 26 cases expressed nm23 mRNA at higher levels in primary tumor tissue than in corresponding non-neoplastic mucosa. No obvious correlation was observed between clinico-pathological features and LOH of nm23 gene or nm23 mRNA expression. On the other hand, 52% of the gastric carcinomas showed reduction of nm23 immunoreactivity in the metastatic tumor of regional lymph nodes, as compared to the primary tumor. Interestingly, 71% of the gastric carcinomas showed weaker nm23 immunoreactivity in the liver metastasis than in the primary tumor. These results suggest that nm23 overexpression is linked with development of gastric carcinomas and the decrease in expression of nm23 participates in metastasis.     

Cd20 Expression and Effects on Outcome of Relapsed/Refractory Diffuse Large B Cell Lymphoma after Treatment with Rituximab

Introduction: Down regulation of CD20 expression has been reported in diffuse large B cell lymphoma (DLBCL)).Therefore, it is important to determine whether chemotherapy with rituximab induces CD20 down regulation and effectssurvival. Objectives: To determine the incidence of down regulation of CD20 expression in relapsed DLBCL aftertreatment with rituximab and to compare outcomes and assess pattern of relapse between CD20 negative and CD20positive cases. Methodology: We retrospectively reviewed patients with relapsed DLBCL who received rituximab inthe first line setting at Aga Khan University Hospital between January 2007 and December 2014. Data were recordedon predesigned questionnaires, with variables including demographics, details regarding date of diagnosis and relapse,histology, staging, international prognostic index, treatment and outcomes at initial diagnosis and at relapse. The Chisquare test was applied to determine statistical significance between categorical variables. Survival curves were generatedby the Kaplan–Meier method. Results: A total of 54 patients with relapsed DLBCL were included in our study, 38 (70%) males and 16(30%) females. Some 23 (43%) patients were at stage IV at the time of diagnosis and 34 (63%) had Bsymptoms. The most frequent R-IPI at diagnosis was II in 24 (44%) patients. Only 6 (11%) did not show CD20 expressionon re-biopsy for relapsed/refractory disease, 2 with CD20 negative DLBCL responding to second line chemotherapy.A complete response after salvage chemotherapy was noted in 16 (29.6%) cases with relapsed/refractory DLBCL.Seven (13%) patients underwent an autologous bone marrow transplant as consolidation after second line treatment.Median overall survival was 18 months in CD20 positive vs. 13 months in CD20 negative patients. Conclusion: Thisstudy demonstrated that a small percentage of patients treated with rituximab lose their CD20 expression at the timeof relapse. However, it is unclear whether this is associated with an inferior outcome.