The Prognostic Role of HuR Varies Between Different Subtypes of Breast Cancer Patients: Data Mining and Retrospective Analysis.

Objective: Human-antigen R (HuR) is an RNA-binding protein, which regulates the expression of several oncogenes and tumor suppressor genes through post-transcriptional mechanisms. But the role of HuR in breast cancer remains controversial. The aim of this study was to verify the association between cytoplasmic HuR level and prognosis of breast cancer patients. Methods: Data mining from the Human Protein Atlas (HPA) and Kaplan-Meier Plotter (KMP) databases was performed. Then, 394 patients with stage I-III primary breast cancer were enrolled between January 2005 and December 2016. We investigated the association between cytoplasmic HuR level and clinicopathological characteristics or survival of these patients. Immunohistochemical analysis was performed to determine HuR expression level. SPSS 21.0 statistical software was used for analysis. Results: In the HPA and KMP datasets, HuR protein and mRNA expression level were not significantly associated with overall survival of all breast cancer patients enrolled. Results from our 394 patients indicated that higher expression level of cytoplasmic HuR was associated with larger tumor size, lymph node positive, ER negative and triple-negative subtype. For all patients enrolled, the results indicated that compared with HuR negative patients, the DFS (disease-free survival) of HuR 1+ was longer (60.5% vs 78.8, P=0.053, HR=0.616, 95% CI: 0.378-1.005), the P value was borderline. In the triple-negative breast cancer (TNBC) subgroup, HuR positive patients had significantly longer DFS than HuR negative patients (65.5% vs 30.8%, P=0.001, HR=0.345, 95% CI: 0.180-0.658). In the HR+HER2- subgroup, HuR low (0~1+) patients had significantly longer OS than HuR high (2+~3+) patients (97.0% vs 89.5%, P=0.033, HR=2.482, 95% CI: 1.074-5.736). Conclusion: In conclusion, our results revealed that higher expression level of HuR was related to aggressive biological characteristics which supported the findings from previous researches. In the HR+HER2- subgroup, lower HuR expression level patients had better survival time, while in the TNBC subgroup we got the opposite results. Our work indicated that HuR might play different roles in different breast cancer subtypes.

Polymorphisms in PARP1 predict disease-free survival of triple-negative breast cancer patients treated with anthracycline/taxane based adjuvant chemotherapy.

Triple-negative breast cancer (TNBC) is a highly aggressive disease and of poor prognosis. It is very important to identify novel biomarkers to predict therapeutic response and outcome of TNBC. We investigated the association between polymorphisms in PARP1 gene and clinicopathological characteristics or survival of 272 patients with stage I-III primary TNBC treated with anthracycline/taxane based adjuvant chemotherapy. We found that after adjusted by age, grade, tumor size, lymph node status and vascular invasion, rs7531668 TA genotype carriers had significantly better DFS rate than TT genotype carriers, the 5 y DFS was 79.3% and 69.2% (P = 0.046, HR 0.526 95% CI 0.280-0.990). In lymph node negative subgroup, DFS of rs6664761 CC genotype carriers was much better than TT genotype carriers (P = 0.016, HR 0.261 95% CI 0.088-0.778) and DFS of rs7531668 AA genotype carriers was shorter than TT genotype carriers (P = 0.015, HR 3.361 95% CI 1.259-8.969). In subgroup of age ≤ 50, rs6664761 TC genotype predicted favorable DFS than TT genotype (P = 0.042, HR 0.405 95% CI 0.170-0.967). Polymorphisms in PARP1 gene had no influence on treatment toxicities. After multivariate analysis, tumor size (P = 0.037, HR = 2.829, 95% CI: 1.063-7.525) and lymph node status (P < 0.001, HR = 9.943, 95% CI: 2.974-33.243) were demonstrated to be independent prognostic factors. Our results suggested that polymorphisms in PARP1 gene might predict the DFS of TNBC patients treated with anthracycline/taxane based adjuvant chemotherapy.

Polymorphisms in AURKA and AURKB are associated with the survival of triple-negative breast cancer patients treated with taxane-based adjuvant chemotherapy.

PURPOSE: Triple-negative breast cancer (TNBC) is more than a single disease. Identifying biomarkers to further subdivide TNBC patients with distinct outcome is of great importance. It has been reported that single-nucleotide polymorphisms (SNPs) in Aurora kinase A (AURKA) or Aurora kinase B (AURKB) are associated with the risk and survival of several cancers. But till now, there is no research about these polymorphisms in TNBC patients. MATERIALS AND METHODS: In this study, we investigated the association between polymorphisms in AURKA or AURKB gene and prognosis of TNBC patients treated with taxane-based adjuvant chemotherapy. A total of 273 TNBC patients were enrolled. Haploview 4.2 software was used to identify Tag SNPs. Genotyping was conducted using the MassARRAY MALDI-TOF system. RESULTS: We found that AURKA rs6099128 GG genotype carriers had significantly worse overall survival (OS) than TT+ TG genotype carriers (P = 0.003, HR = 12.499, 95% CI = 2.357-66.298). AURKB rs11651993 TT genotype carriers had better disease-free survival (DFS) than TC + CC genotype carriers (P = 0.018, HR = 1.876, 95% CI = 1.116-3.154). AURKB rs2289590 CC genotype carriers had worse DFS than CA + AA genotype carriers (P = 0.021, HR = 0.536, 95% CI = 0.315-0.912). After subgroup analysis, rs11651993 TC + CC genotype predicted worse DFS in subgroups of age ≤ 50, post-menopausal, grade unknown (UK), tumor size >2 cm, and lymph node negative. Rs2289590 CA + AA genotype could predict favorable DFS in pre-menopausal, grade 3 and lymph node-positive patients. CONCLUSION: We first demonstrated that polymorphisms in AURKA or AURKB gene might predict the OS or DFS of TNBC patients treated with taxane-based adjuvant chemotherapy.

Quality of Life in Patients with Dementia with Lewy Bodies.

Dementia with Lewy bodies (DLB) is a complex, multisymptom disorder. When making decisions regarding the treatment of DLB, the patient's quality of life (QoL) should always be the main consideration. To our knowledge, this is the first review article focusing on the QoL in DLB patients. We searched the PubMed database using the keywords "quality of life" and "dementia with Lewy bodies." Previously, no specific instrument had been developed for assessing the QoL in DLB patients. Patients with DLB have a decreased QoL compared to patients with Alzheimer's disease, which is reportedly caused by several factors including level of independence in instrumental activities of daily living, whether the patient is living with the caregiver, apathy, delusion, and dysautonomia. The direct effect of visual hallucination, sleep, and movement disorders on the QoL in DLB patients has not been previously studied. The role of cognitive function on the QoL is still controversial. In a randomized controlled study, memantine may improve the QoL in PDD or DLB patients. We concluded that it is important to develop a specific instrument to assess the QoL in DLB patients. Furthermore, there is an urgent need for large clinical trials to identify factors associated with the QoL and how they can be managed.

Genetic variants in miRNA machinery genes associated with clinicopathological characteristics and outcomes of gastric cancer patients.

BACKGROUND: Polymorphisms in miRNA machinery genes have been proved to be related to risk or survival of several kinds of cancers, but the results are controversial and the role of these polymorphisms in gastric cancer remains uncertain. In our study, we investigated the association between five genetic variants in miRNA machinery genes ( DICER, RAN, XPO5 [name of the gene]) and clinical outcomes in Chinese gastric cancer patients. METHODS: A total of 96 patients with stage IB-III gastric cancer treated with radical gastrectomy and adjuvant chemotherapy of oxaliplatin and fluorouracils were analyzed. The MassARRAY MALDI-TOF system was used to determine the genotypes. RESULTS: DICER rs3742330 AG+GG genotype was associated with more advanced T stage compared to AA genotype ( P=0.009). More patients with XPO5 rs2257082 CC genotype had poorly differentiated tumors compared with CT+TT genotype carriers. After adjustment by age, sex, differentiation, T stage, and lymph node status, XPO5 rs2257082 CC genotype carriers were found to have worse disease-free survival than CT+TT genotype carriers (adjusted HR 3.099; 95% CI 1.270, 7.564; P=0.013), carriers of RAN rs14035 CC genotype had higher three-year OS rate than carriers of CT+TT genotype (adjusted HR 3.174; 95% CI 1.010, 9.973; P=0.048). CONCLUSIONS: These results indicated that genetic variants in miRNA machinery genes might be associated with the clinicopathological features and prognosis of completely resected gastric cancer patients.

The impacts of single nucleotide polymorphisms in genes of cell cycle and NF-kB pathways on the efficacy and acute toxicities of radiotherapy in patients with nasopharyngeal carcinoma.

Radiotherapy is one of the primary choices for the treatment of nasopharyngeal carcinoma (NPC) and may result in severe radiotoxicities on normal tissues. Single nucleotide polymorphisms (SNPs) in genes of cell cycle and NF-κB pathways have been linked with the prognoses of various cancers. The aim of this study was to explore whether SNPs of genes involved in cell cycle and NF-κB pathways are associated with responses to radiotherapy in NPC patients. We selected 3 SNPs in cell cycle pathway and 5 SNPs in NF-κB pathway and genotyped them in 154 NPC patients treated with radiotherapy. Multivariate logistic regression was used to determine the association of these 8 SNPs with the responses to radiotherapy. We observed that cyclin-dependent kinase inhibitor gene CDKN2A rs3088440 was significantly related with a poorer treatment efficacy on the primary tumor and cervical lymph node after radiotherapy, and also with a decreased risk of grade 3-4 acute radiation-induced myelosuppression. In some subgroups, cyclin D1 gene CCND1 rs9344 and inhibitor of κB kinase gene IKBKB rs12676482 were related with the grade 3-4 acute radiation-induced myelosuppression, and CCND1 rs9344 was also associated with grade 3-4 acute radiation-induced oral mucositis. The current results reveal that SNPs in genes of cell cycle pathwayand NF-κB pathway have the potential to predict the clinical responses to radiotherapy for NPC patients.

DROSHA rs10719 T>C is associated with lymph node metastasis and clinical stage of gastric cancer patients.

It has been proved that polymorphisms in DROSHA are related to the risk and outcomes of several cancers. In our study, 97 patients with stage I-III gastric cancer treated with radical gastrectomy and adjuvant chemotherapy of oxaliplatin and fluoropyrimidines were analyzed. MassARRAY MALDI-TOF system was used to determine the genotypes. The 2-year DFS rate was 60.8% and the 3-year OS rate was 73.8%. In dominant model, we found that rs10719 TC+CC genotype carriers were less likely to develop lymph node metastasis (P=0.031). Compared with TC+CC genotype carriers, more patients with TT genotype were in stage III (P=0.021). The 3-year OS was significantly different for patients with or without lymph node metastasis (89.3% vs 63.3%, P=0.013) and for patients with stage I-III disease (100.0%, 88.6% and 55.8%, P=0.015). After the multi-variants' cox regression analysis, lymph node status (P=0.014, RR: 9.556, 95% CI: 1.586-57.590) was found to be an independent prognostic factor for these patients. These results suggested that DROSHA rs10719 T>C may be associated with lymph node metastasis and clinical stage of gastric cancer in a Chinese population.

Polymorphism in miR-146a associated with clinical characteristics and outcomes in gastric cancer patients treated with adjuvant oxaliplatin and fluoropyrimidines.

PURPOSE: Polymorphism in miR-146a (rs2910164) has been reported to be associated with gastric cancer risk in the Chinese population. We aimed at evaluating the relationship between rs2910164 and the clinical characteristics and outcomes in stage IB-III gastric cancer patients treated with adjuvant chemotherapy after surgery. MATERIALS AND METHODS: Ninety-eight patients with stage IB-III gastric cancer treated with surgical resection followed by adjuvant chemotherapy of oxaliplatin and fluoropyrimidines were included in the analysis. Genomic DNA was extracted from peripheral blood sample of all patients. Polymerase chain reaction-based restriction fragment length polymorphism assay was used to determine the genotypes. RESULTS: The 2-year disease-free survival rate was 63%, and the 3-year overall survival (OS) rate was 73.4%. In dominant model, we found that rs2910164 GC + CC (G: guanine, C: cytosine) genotype carriers were less likely to develop lymph node metastasis (P=0.059). The 3-year OS was significantly different for patients with or without lymph node metastasis (89.3% vs 63.7%, P=0.015) and for patients with stage I-III disease (100.0%, 88.6%, and 56.9%; P=0.018). The 3-year OS for GC + CC carriers was significantly higher than for GG carriers (75.1% vs 66.7%, P=0.041). After the multivariant Cox regression analysis, histological grade (P=0.033, relative risk: 5.116, 95% confidence interval: 1.145-22.865) and lymph node status (P=0.031, relative risk: 6.648, 95% confidence interval: 1.191-37.118) were found to be independent prognostic factors for these patients. CONCLUSION: rs2910164 could be associated with the lymph node metastasis and prognosis of Chinese gastric cancer patients treated with oxaliplatin and fluoropyrimidines after surgical resection.

A randomized clinical trial comparing prophylactic upper versus whole-neck irradiation in the treatment of patients with node-negative nasopharyngeal carcinoma.

BACKGROUND: This study sought to compare the clinical outcomes of upper versus whole-neck prophylactic irradiation in the treatment of patients with node-negative nasopharyngeal carcinoma (NPC). METHODS: Between November 2005 and June 2012, 301 patients with node-negative NPC were randomly assigned to receive primary plus prophylactic upper neck irradiation (UNI, 153 patients) or primary plus whole-neck irradiation (WNI, 148 patients). Patients in both groups received irradiation to the primary tumor and the upper neck nodal regions, and patients in the WNI group also received irradiation to the lower neck. The main endpoint of the study was to compare the lower neck control rate between the 2 groups. RESULTS: With a median follow-up period of 39 months (range, 6-84 months), no patient in either group had a cervical node relapse. The overall survival at 3 years was 89.5% (95% confidence interval [CI] = 84.1%-95.0%) in the UNI group and 87.4% (95% CI = 81.4%-93.5%) in the WNI group (hazard ratio [HR] = 0.866, 95% CI = 0.41-1.82; P = .70). The 3-year relapse-free survival rate was 89.8% and 89.3% (95% CI = 84.2%-95.3% and 83.7%-94.8%, HR = 0.914, 95% CI = 0.42-2.00; P = .82), and the 3-year metastasis-free survival rate was 91.7% and 90.9% (95% CI = 87.0%-96.5% and 85.7%-96.1%) for the UNI and WNI groups, respectively (HR = 1.007, 95% CI = 0.44-2.32; P = .99). CONCLUSIONS: Prophylactic upper neck irradiation is sufficient for patients with node-negative NPC.