Deciphering the structure,function, expression and regulation of aquaporin-5 in cancer evolution

In recent years, the morbidity rate resulting from numerous types of malignant tumor has increased annually, and the treatment of tumors has been attracting an increasing amount of attention. A number of recent studies have revealed that the water channel protein aquaporin-5 (AQP5) has become a major player in multiple types of cancer. AQP5 is abnormally expressed in a variety of tumor tissues or cells and has multiple effects on certain biological functions of tumors, such as regulating the proliferation, apoptosis and migration of tumor cells. It has been suggested that AQP5 may play an important role in the process of tumor development, opening up a new field of tumor research. The present review highlighted the structure of AQP5 and its role in tumor progression. Furthermore, the expression of AQP5 in different malignant neoplasms was summarized. In addition, the influence of not only drugs, but also different compounds on AQP5 were summarized. In conclusion, according to the findings in the present review, AQP5 has potential as a novel therapeutic target in human cancer, and other AQPs should be similarly investigated.     

Colorectal cancer screening in the COVID-19 era

Colorectal cancer (CRC) is the third most diagnosed form of cancer and second most deadly cancer worldwide. Introduction of better screening has improved both incidence and mortality. However, as the coronavirus disease 2019 (COVID-19) pandemic began, healthcare resources were shunted away from cancer screening services resulting in a sharp decrease in CRC screening and a backlog of patients awaiting screening tests. This may have significant effects on CRC cancer mortality, as delayed screening may lead to advanced cancer at diagnosis. Strategies to overcome COVID-19 related disruption include utilizing stool-based cancer tests, developing screening protocols based on individual risk factors, expanding telehealth, and increasing open access colonoscopies. In this review, we will summarize the effects of COVID-19 on CRC screening, the potential long-outcomes, and ways to adapt CRC screening during this global pandemic.     

The expression of vascular endothelial growth factor (VEGF)/ endostatin (ES) and VEGF receptor 2 (VEGFR2)/ES is associated with NSCLC prognosis

Objective The aim of our study was to detect the expression of angiogenesis inhibitory proteins and angiogenesis promotive proteins in the postoperative tumor tissue of non-small cell lung cancer (NSCLC) patients. We also investigated the relationship of protein expression with clinical characteristics and prognosis. Methods We examined the expression of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), and endostatin (ES) proteins in 255 specimens resected from NSCLC patients, using immune histochemistry (IHC). We then evaluated the relationships between the expression of the three proteins and clinical characteristics such as stage, histological type, differentiation, gender, tobacco use, and age. According to the value of VEGF/ES, we divided the cohort into angiogenesis-promoting group A, angiogenesis-inhibiting group A, and balance group A. The survival differences in the three groups were evaluated to determine the prognostic value of VEGF/ES. Similarly, we tested the prognostic value of VEGFR2/ES. Results VEGF-positive expression was observed in 93 patients (36.4％). VEGF expression was not correlated with the clinical characteristics. VEGFR2-positive expression was observed in 103 patients (40.4％). The expression of VEGFR2 was correlated with the clinical stage (χ2 = 21.414, P = 0.045) and histological type (χ2 = 26.911, P = 0.008). ES-positive expression was observed in 140 patients (54.9％). The expression of ES was correlated with the clinical stage (χ2 = 26.504, P = 0.009). When evaluating the prognostic values of VEGF/ES and VEGFR2/ES, the prognosis of the angiogenesis balance group was similar to that of the angiogenesis-inhibiting group. The minimum survival time was observed in the angiogenesis-promoting group. Conclusion VEGF/ES and VEGFR2/ES in resected tumors have prognostic value in postoperative NSCLC patients. The survival time of the population with predominant angiogenic factors was short.     

BRCA1-associated protein 1 serves as a tumor suppressor in hepatocellular carcinoma by deubiquitinating and stabilizing PTEN

BRCA1-associated protein 1 (BAP1) or its mutants have been known to play critical regulatory roles in tumor biology, yet their role in hepatocellular carcinoma (HCC) remains largely unclear. In this study, we detected the mutations of all the exons of BAP1 in 105 HCC patients using Sanger sequencing, and found eight somatic mutations in 6 (5.71%) patients. We also found that the mRNA and protein levels of BAP1 were markedly downregulated in HCC versus the adjacent non-tumor tissues. Wild-type BAP1 but not mutant BAP1 significantly inhibited HCC cell proliferation, invasion, epithelial-mesenchymal transition (EMT) in vitro, and tumor progression and metastasis in vivo. Mechanistically, BAP1 complexed with PTEN and stabilized PTEN via deubiquitination and, furthermore, negatively regulated HCC cell EMT by deactivating the AKT/GSK-3β/Snail pathway. However, those tumor-inhibitory effects of BAP1 were abolished by inactivating mutations. Clinically, low BAP1 expression was positively correlated to aggressive tumor phenotypes, which also independently associated with poorer recurrence-free survival and overall survival after curative hepatectomy. Conclusively, our results indicate that BAP1, significantly downregulated, somatically mutated and negatively regulating EMT in HCC, serves as a tumor suppressor of HCC by deubiquitinating and stabilizing PTEN.     

Association between the polygenic liabilities for prostate cancer and breast cancer with biochemical recurrence after radical prostatectomy for localized prostate cancer

Prostate and breast cancers are hormone-related malignancies and are characterized by a complex interplay of hundreds of susceptibility loci throughout the genome. Prostate cancer could be inhibited by eliminating androgens through castration or estrogen administration, thus facilitating long-term treatment of prostate cancer; however, the role of estrogen in prostate cancer remains unclear. This study aimed to determine whether polygenic risk scores (PRSs) comprising combinations of genome-wide susceptibility variants influence the clinical outcomes of prostate cancer patients. The study subjects were recruited from four medical centers in Taiwan, and genome-wide genotyping data were obtained from 643 prostate cancer patients. We derived the PRS for prostate cancer (PRS-PC) and for breast cancer (PRS-BC) for each patient. The association between the PRS-PC/PRS-BC at the age of prostate cancer onset and recurrence within seven years was evaluated using a regression model adjusted for population stratification components. A higher PRS-PC was associated with an earlier onset age for prostate cancer (beta in per SD increase in PRS = -0.89, P = 0.0008). In contrast, a higher PRS-BC was associated with an older onset age for prostate cancer (beta = 0.59, P = 0.02). PRS-PC was not associated with the risk of recurrence (hazard ratio = 1.03, P = 0.67), whereas a higher PRS-BC was associated with a low recurrence risk (hazard ratio = 0.86, P = 0.03). These results indicate that the genetic predisposition to breast cancer is associated with a low risk of prostate cancer recurrence. Further studies are warranted to explore the role of breast cancer susceptibility variants and estrogen signaling in prostate cancer progression.     

Establishment and verification of prognostic model for gastric cancer based on autophagy-related genes

Autophagy played a significant role in the development of cancer. In this study, we explored the value of autophagy-associated genes in gastric cancer. RNA sequencing and clinical information containing 375 gastric cancer and 32 normal tissues were gathered from the TCGA portal. Then we stochastically allocated the autophagy-associated genes (AAGs) to training and testing groups. Next, we screened the discrepantly expressed AAGs and the prognostic AAGs by Cox regression analysis and Lasso regression analysis. Afterwards, we structured the model by using the prognostic AAGs and plotted Kaplan-Meier (KM) and receiver operating characteristic (ROC) curves to verify the performance of models in both groups. Besides, we utilized Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to explore the molecular mechanisms of AAGs in gastric cancer. Finally, we demonstrated discrepant expression of AAGs within gastric cancer and non-tumor tissues at protein level with immunohistochemistry. 28 discrepantly expressed AAGs were screened from the TCGA database which contained 375 gastric cancer and 32 non-tumor samples. Cox and Lasso regression analyses were performed in training group and then we got 5 prognostic AAGs to establish the prognostic model. The patients who had high risk possessed worse overall survival (OS) both in training group (5-year OS, 47.6% vs 23.1%; P < 0.0001) and test group (5-year OS, 49.2% vs 0%, P=0.019). The proportion under ROC curves (AUC) were significant both in training group and test group (5-year AUC, 0.736 vs 0.809). Through this study, we constructed a model for gastric cancer patients which may provide individual treatment and superior prognosis.     

成釉细胞瘤预后评估——基于SEER数据库的研究

目的 成釉细胞瘤(AM)是罕见牙源性肿瘤,易复发、浸润生长,本研究旨在探讨成釉细胞瘤预后因素。方法 基于SEER数据库筛选成釉细胞瘤 207例,构建Cox回归模型并绘制诺莫图预测总生存。回顾性分析湖南省肿瘤医院 61例临床资料,用Cox回归分析影响复发的独立因素。结果 基于SEER数据库评估,年龄、肿瘤大小、手术方式、放疗均是影响AM患者总生存的重要因素,构建列线图,一致性指数为0.821,表明预测模型具有中等准确度。受试者工作曲线显示1、3、5、10年的曲线下面积分别为0.852、0.869、0.856、0.879,表明预测模型具有较好的敏感性和特异性。Kaplan-Meier生存分析显示高风险组总生存低于低风险组(P<0.001)。基于回顾性分析,临床症状、手术类型是影响局部复发率的独立因素;面部肿痛,相对于其他症状复发率更低,根治手术相对于姑息手术可降低复发率。结论 年龄、肿瘤大小、手术方式、放疗可能是影响总生存的重要因素;手术方式、临床症状可能是影响复发率的独立因素。