Cancers, Vol. 10, Pages 328: Clinical Impact of Epithelial-to-Mesenchymal Transition Regulating MicroRNAs in Pancreatic Ductal Adenocarcinoma

Cancers, Vol. 10, Pages 328: Clinical Impact of Epithelial-to-Mesenchymal Transition Regulating MicroRNAs in Pancreatic Ductal Adenocarcinoma

Cancers doi: 10.3390/cancers10090328

Authors: Sameer Abdallah Dhayat Max Michael Traeger Jan Rehkaemper Anda Jana Stroese Konrad Steinestel Eva Wardelmann Iyad Kabar Norbert Senninger

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive carcinoma entities worldwide with early and rapid dissemination. Recently, we discussed the role of microRNAs as epigenetic regulators of Epithelial-to-Mesenchymal Transition (EMT) in PDAC. In this study, we investigated their value as diagnostic and prognostic markers in tissue and blood samples of 185 patients including PDAC, non-malignant pancreatic disorders, and age-matched healthy controls. Expression of the microRNA-200-family (microRNAs -141, -200a, -200b, -200c, -429) and microRNA-148a was significantly downregulated in tissue of PDAC Union internationale contre le cancer (UICC) Stage II. Correspondingly, stromal PDAC tissue showed strong expression of Fibronectin, Vimentin, and ZEB-1 (Zinc finger E-box-binding homeobox) versus low expression of E-cadherin. Transient transfection of microRNA-200b and microRNA-200c mimics resulted in the downregulation of their key target ZEB-1. Inversely, blood serum analyses of patients with PDAC UICC Stages II, III, and IV showed a significant over-expression of microRNA-200-family members, microRNA-148a, microRNA-10b, and microRNA-34a. Correspondingly, Enzyme-linked Immunosorbent Assay (ELISA) analyses revealed a significant over-expression of soluble E-cadherin in serum samples of PDAC patients versus healthy controls. The best diagnostic accuracy to distinguish between PDAC and non-PDAC in this patient collective could be achieved in tissue by microRNA-148a with an area under the receiver-operating-characteristic (ROC) curve (AUC) of 0.885 and in blood serum by a panel of microRNA-141, -200b, -200c, and CA.19-9 with an AUC of 0.890. Both diagnostic tools outreach the diagnostic performance of the currently most common diagnostic biomarker CA.19-9 (AUC of 0.834). Kaplan Meier survival analysis of this patient collective revealed an improved overall survival in PDAC patients with high expression of tissue-related microRNA-34a, -141, -200b, -200c, and -429. In conclusion, EMT-regulating microRNAs have great potential as liquid and solid biopsy markers in PDAC patients. Their prognostic and therapeutic benefits remain important tasks for future studies.

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Correction to: Histone demethylase KDM4D promotes gastrointestinal stromal tumor progression through HIF1β/VEGFA signalling

After the publication of this work [1] an error was noticed in Fig. 7e, in which the incorrect information is shown. The updated figure included in this correction now shows the quantification of tumor microvessel density. This correction does not affect the findings or conclusions of the article. Nevertheless, we apologize for the inconvenience.

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Epigenetic markers in basal cell carcinoma: universal themes in oncogenesis and tumor stratification? - a short report

Abstract

Background

Advanced basal cell carcinomas (BCCs) suffer from a scarcity of effective treatment options. Previously, we found that the targetable histone methyltransferase EZH2 was upregulated in aggressive BCC subtypes, suggesting that epigenetics may play a role in BCC progression. The purpose of this study was to determine whether EZH2-associated proteins and marks may be employed for the stratification of BCC histologic subtypes.

Methods

Sixty-two specimens (from 61 patients), representing more or less aggressive BCC histologic subtypes and matching non-malignant epidermal cells, were included in this study. Immunohistochemistry of H3K27me3, 5hmC, NSD2, MOF and JARID1B was performed to assess their putative associations with BCC histologic subtypes, as well as with EZH2 and Ki67 expression levels.

Results

We found that H3K27me3 and 5hmC upregulation was positively correlated with the occurrence of a less aggressive BCC histology. The modifications were also positively correlated with each other. Interestingly, we found that they were negatively correlated with the expression of EZH2, a marker for an aggressive BCC histology. The levels of NSD2, MOF, H3K27me3 and 5hmC were found to be universally upregulated in BCCs versus non-malignant epidermal cells.

Conclusions

Our data reveal an EZH2-associated epigenetic marker profile that correlates with histologic signs of BCC aggressiveness. Our findings may have diagnostic and therapeutic implications, and indicate that epigenetic markers may be shared even with relatively less aggressive tumor types, thereby suggesting universal themes.

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A Very Rare Complication of Hepatitis A Infection: Acute Myocarditis—A Case Report with Literature Review

Hepatitis A is a common viral infection with a benign course but in rare cases can progress to acute liver failure. It usually presents with abdominal pain, nausea, vomiting, diarrhea, jaundice, anorexia, or asymptomatically, but it can also present atypically with relapsing hepatitis and prolonged cholestasis. In addition, extrahepatic manifestations have been reported, including urticarial and maculopapular rash, acute kidney injury, autoimmune hemolytic anemia, aplastic anemia, acute pancreatitis, mononeuritis, reactive arthritis, glomerulonephritis, cryoglobulinemia, Guillain–Barre syndrome, and pleural or pericardial effusion. A rare manifestation of hepatitis A is acute myocarditis. We report a case of a young woman who presented with "flu-like symptoms" and was found to have severe elevation of liver enzymes due to acute hepatitis A infection. On her 3rd day of admission, the patient developed chest pain and nonspecific electrocardiographic changes. Her troponins rose to 16.4  ng/mL, and a transthoracic echocardiogram revealed global hypokinesis and a depressed ejection fraction at 30%. A CT angiography showed no evidence of significant coronary artery disease. The patient was managed supportively, and symptoms and laboratory findings slowly improved over the next 7 days. Her chest pain resolved and a follow-up echocardiogram showed improved ejection fraction to 45%.

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Oplopanax horridus: Phytochemistry and Pharmacological Diversity and Structure-Activity Relationship on Anticancer Effects

Oplopanax horridus, well-known as Devil's club, is probably the most important ethnobotanical to most indigenous people living in the Pacific Northwest of North America. Compared with the long history of traditional use and widespread distribution in North America, the study of O. horridus is relatively limited. In the past decade, some exciting advances have been presented on the phytochemistry and pharmacological diversity and structure-activity relationship on anticancer effects of O. horridus. To date, no systematic review has been drafted on the recent advances of O. horridus. In this review, the different phytochemicals in O. horridus are compiled, including purified compounds and volatile components. Animal and in vitro studies are also described and discussed. Especially, the potential structural-activity relationship of polyynes on anticancer effects is highlighted. This review aimed to provide comprehensive and useful information for researching O. horridus and finding potential agents in drug discovery.

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Major Depression in Chinese Medicine Outpatients with Stagnation Syndrome: Prevalence and the Impairments in Well-Being

Stagnation syndrome, a diagnostic entity in traditional Chinese medicine (TCM), has been long regarded as the TCM counterpart of major depression in Western medicine. The study investigated the prevalence of major depression among stagnation syndrome patients and evaluated their well-being and functioning outcomes. In total, 117 patients diagnosed with stagnation syndrome were measured using Stagnation Scale, the Patient Health Questionnaire-9 (PHQ-9), and the Body-Mind-Spirit Well-Being Inventory. Results indicate major depression among stagnation syndrome patients was characterized by a high co-occurrence rate and worse physical, mental, and functional outcomes. More than one-quarter (26.5%) of the patients met the DSM-V diagnostic criteria for major depression and over half (53%) exceeded the PHQ-9 cutoff (score above 10) for moderate/severe depression symptoms. The wellness of the stagnation syndrome patients was worse (M = 298.2, SD = 66.5) than that of the general population (M = 360.9, SD = 79.9), with a large Cohen's value of 0.9. The "wellness outlook" of the depressed stagnation syndrome patients appeared grimmer (M = 252.3, SD = 52.2). The correlation between stagnation and depression was higher for affective symptoms than somatic symptoms. Physical distress did not mediate the relationship between stagnation and daily functioning. These might suggest that stagnation syndrome and major depression may share some similar psychological mechanisms.

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Sarcomatoid Variant of Bladder Carcinoma: A Case Report

A 59-year-old man was referred to our hospital complaining of asymptomatic gross hematuria. Cystoscopy revealed a papillary tumor 8 cm in diameter filling the bladder. The patient underwent transurethral resection of the bladder tumor. The pathological findings revealed the sarcomatoid variant of urothelial carcinoma with a heterologous osteosarcomatous element. He had no metastasis according to our imaging analyses; thus, we planned radical cystectomy after two courses of neoadjuvant chemotherapy (gemcitabine and cisplatin). Following chemotherapy, enlarged pelvic lymph nodes were noted, and extremely aggressive local progression of the bladder tumor was confirmed. The patient ultimately died 6 months after his initial visit to our hospital.
Case Rep Oncol 2018;11:633–637

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