Prognostic Significance of Phosphatase of Regenerating Liver-3 Expression in Ovarian Cancer

AbstractWe investigated the prognostic significance and the underlying mechanism of increased bone marrow (BM) 2-(18F) fluoro-2-deoxy-D-glucose as a tracer (FDG)-uptake in patients with gynecological cancer. A list of patients diagnosed with cervical, endometrial, and ovarian cancer from January 2008 to December 2014 were identified. Then, through chart reviews, 559 patients who underwent staging by FDG-positron emission tomography (PET)/computed tomography (CT) and subsequent surgical resection were identified, and their clinical data were reviewed retrospectively. BM FDG-uptake was evaluated using maximum standardized uptake value (SUVmax) and BM-to-aorta uptake ratio (BAR). As a result, we have found that increased BAR was observed in 20 (8.7%), 21 (13.0%), 21 (12.6%) of cervical, endometrial, and ovarian cancer, respectively, and was associated with significantly shorter survival. Increased BAR was also closely associated with increased granulopoiesis. In vitro and in vivo experiments revealed that tumor-derived granulocyte colony-stimulating factor (G-CSF) was involved in the underlying causative mechanism of increased BM FDG-uptake, and that immune suppression mediated by G-CSF-induced myeloid-derived suppressor cells (MDSCs) is responsible for the poor prognosis of this type of cancer. In conclusion, increased BM FDG-uptake, as represented by increased BAR, is an indicator of poor prognosis in patients with gynecological cancer.

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Comprehensive Analysis of the Expression of Key Genes Related to Hippo Signaling and Their Prognosis Impact in Ovarian Cancer

Diagnostics ◽

10.3390/diagnostics11020344 ◽

2021 ◽

Vol 11 (2) ◽

pp. 344

Author(s):

Paul Kubelac ◽

Cornelia Braicu ◽

Lajos Raduly ◽

Paul Chiroi ◽

Andreea Nutu ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Progression ◽

Prognostic Value ◽

Prognostic Significance ◽

Expression Level ◽

Additional Patient ◽

Tumor Control ◽

Hippo Signaling ◽

Patient Cohort ◽

Qrt Pcr

The Hippo signaling pathway, one of the most conserved in humans, controlling dimensions of organs and tumor growth, is frequently deregulated in several human malignancies, including ovarian cancer (OC). The alteration of Hippo signaling has been reported to contribute to ovarian carcinogenesis and progression. However, the prognostic roles of individual Hippo genes in OC patients remain elusive. Herein we investigated the expression level and prognostic value of key Hippo genes in OC using online databases, followed by a qRT-PCR validation step in an additional patient cohort. Using the GEPIA database, we observed an increased level for TP53 and reduced expression level for LATS1, LATS2, MST1, TAZ, and TEF in tumor tissue versus normal adjacent tissue. Moreover, LATS1, LATS2, TP53, TAZ, and TEF expression levels have prognostic significance correlated with progression-free survival. The qRT-PCR validation step was conducted in an OC patient cohort comprising 29 tumor tissues and 20 normal adjacent tissues, endorsing the expression level for LATS1, LATS2, and TP53, as well as for two of the miRNAs targeting the TP53 gene, revealing miR-25-3p upregulation and miR-181c-5p downregulation. These results display that there are critical prognostic value dysregulations of the Hippo genes in OC. Our data demonstrate the major role the conserved Hippo pathway presents in tumor control, underlying potential therapeutic strategies and controlling several steps modulated by miRNAs and their target genes that could limit ovarian cancer progression.

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Evaluation of Prognostic and Predictive Significance of Circulating MicroRNAs in Ovarian Cancer Patients

Disease Markers ◽

10.1155/2017/3098542 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 22

Author(s):

Ann Rita Halvorsen ◽

Gunnar Kristensen ◽

Andy Embleton ◽

Cybil Adusei ◽

Maria Pilar Barretina-Ginesta ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Prognostic Significance ◽

Response To Treatment ◽

Rank Test ◽

Specific Marker ◽

High Grade ◽

Standard Chemotherapy ◽

Validation Set ◽

Serous Tumors

Ovarian cancer patients are recognized with poor prognosis. This study aimed to identify microRNAs in plasma for predicting response to treatment and outcome. We have investigated microRNAs in plasma from ovarian cancer patients enrolled in a large multicenter study (ICON7), investigating the effect of adding bevacizumab to standard chemotherapy in patients diagnosed with epithelial ovarian cancer. Patients with different histology, grade, and FIGO stages were included (n=207) in this study. Screening of 754 unique microRNAs was performed in the discovery phase (n=91) using TaqMan Low Density Arrays. The results were validated using single assays and RT-qPCR. Low levels of miR-200b, miR-1274A (tRNALys5), and miR-141 were significantly associated with better survival, confirmed with log-rank test in the validation set. The level of miR-1274A (tRNALys5) correlated with outcome was especially pronounced in the high-grade serous tumors. Interestingly, low level of miR-200c was associated with 5-month prolongation of PFS when treated with bevacizumab compared to standard chemotherapy. We found prognostic significance of miR-200b, miR-141, and miR-1274A (tRNALys5) in all histological types, where miR-1274A (tRNALys5) may be a specific marker in high-grade serous tumors. The level of miR-200c may be predictive of effect of treatment with bevacizumab. However, this needs further validation.

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Regulatory mechanisms of phosphatase of regenerating liver (PRL)-3

Biochemical Society Transactions ◽

10.1042/bst20160146 ◽

2016 ◽

Vol 44 (5) ◽

pp. 1305-1312 ◽

Cited By ~ 14

Author(s):

Teresa Rubio ◽

Maja Köhn

Keyword(s):

Drug Development ◽

Posttranslational Modifications ◽

Human Cancer ◽

Regulatory Mechanisms ◽

Therapeutic Drug ◽

Regenerating Liver ◽

Cancer Types ◽

Tumor Metastases ◽

Phosphatase Of Regenerating Liver ◽

Incomplete Picture

The phosphatase of regenerating liver (PRL)-3 is overexpressed in many human cancer types and tumor metastases when compared with healthy tissues. Different pathways and mechanisms have been suggested to modulate PRL-3 expression levels and activity, giving some valuable insights but still leaving an incomplete picture. Investigating these mechanisms could provide new targets for therapeutic drug development. Here, we present an updated overview and summarize recent findings concerning the different PRL-3 expression regulatory mechanisms and posttranslational modifications suggested to modulate the activity, localization, or stability of this phosphatase.

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