Pan-Cancer Prognostic Role and Targeting Potential of the Estrogen-Progesterone Axis

IntroductionEstrogen receptors (ESRs) and progesterone receptors (PGRs) are associated with the development and progression of various tumors. The feasibility of ESRs and PGRs as prognostic markers and therapeutic targets for multiple cancers was evaluated via pan-cancer analysis.MethodsThe pan-cancer mRNA expression levels, genetic variations, and prognostic values of ESR1, ESR2, and PGR were analyzed using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and cBioPortal. The expression levels of ERa, ERb, and PGR proteins were detected by immunohistochemical staining using paraffin-embedded tissue specimens of ovarian serous cystadenocarcinoma (OV) and uterine endometrioid adenocarcinoma (UTEA). Correlation between immunomodulators and immune cells was determined based on the Tumor and Immune System Interaction Database (TISIDB).ResultsESR1, ESR2, and PGR mRNAs were found to be differentially expressed in different cancer types, and were associated with tumor progression and clinical prognosis. ERa, ERb, and PGR proteins were further determined to be significantly differentially expressed in OV and UTEA via immunohistochemical staining. The expression of ERa protein was positively correlated with a high tumor stage, whereas the expression of PGR protein was conversely associated with a high tumor stage in patients with OV. In patients with UTEA, the expression levels of both ERa and PGR proteins were conversely associated with tumor grade and stage. In addition, the expression levels of ESR1, ESR2, and PGR mRNAs were significantly associated with the expression of immunomodulators and immune cells.ConclusionESR1, ESR2, and PGR are potential prognostic markers and therapeutic targets, as well as important factors for the prediction, evaluation, and individualized treatment in several cancer types.

High KIFC1 expression is associated with poor prognosis in prostate cancer

Kinesins play important roles in the progression and development of cancer. Kinesin family member C1 (KIFC1), a minus end-directed motor protein, is a novel Kinesin involved in the clustering of excess centrosomes found in cancer cells. Recently KIFC1 has shown to play a role in the progression of many different cancers, however, the involvement of KIFC1 in the progression of prostate cancer (PCa) is still not well understood. This study investigated the expression and clinical significance of KIFC1 in PCa by utilizing multiple publicly available datasets to analyze KIFC1 expression in patient samples. High KIFC1 expression was found to be associated with high Gleason score, high tumor stage, metastatic lesions, high ploidy levels, and lower recurrence-free survival. These results reveal that high KIFC1 levels are associated with a poor prognosis for PCa patients and could act as a prognostic indicator for PCa patients as well.

miR-106a-5p Functions as a Tumor Suppressor by Targeting VEGFA in Renal Cell Carcinoma

MicroRNAs (miRNAs) regulate progression of different cancers. Nevertheless, there is limited information regarding the role of miR-106a-5p in renal cell carcinoma (RCC). Herein, we demonstrate that miR-106a-5p levels are drastically decreased in clear cell RCC (ccRCC) tissues and cell lines, which subsequently contribute to a poor patient overall survival and a high tumor stage. By screening and analyzing, we found that miR-106a-5p directly targets the 3 ′ -UTR of the VEGFA mRNA and led to a decrease in VEGFA. This process is important for tumor cells’ growth and colony formation, and overexpression of miR-106a-5p can especially kill kidney tumor cells. Therefore, our data reveal that miR-106a-5p functions as a tumor suppressor by regulating VEGFA and ccRCC may be susceptible to miR-106a-5p therapy.

Clinicopathological and Prognostic Value of Gastric Carcinoma Highly Expressed Transcript 1 in Cancer: A Meta-Analysis

Background. Long noncoding RNA gastric cancer highly expressed transcript 1 (lncRNA GHET1) is often reported to be abnormally expressed in multiple cancers, but the situation is different in different cancers. Therefore, a meta-analysis is necessary to clarify the value of lncRNA GHET1 as a prognostic indicator in cancer. Methods. Relevant research studies on lncRNA GHET1 and cancer were retrieved from three electronic literature databases of Web of Science, PubMed, and OVID. Meanwhile, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to explore the relationship between lncRNA GHET1 expression and survival of cancer patients. The odds ratios (ORs) and 95% CIs were calculated to assess the association of lncRNA GHET1 expression with pathological parameters of cancer patients. Results. The meta-analysis included a total of 11 studies involving 714 cancer patients. The pooled HR suggests that high lncRNA GHET1 expression is associated with poor overall survival. In addition, high expression of lncRNA GHET1 was found to be associated with larger tumor size, poor histological grade, high tumor stage, lymph node metastasis, and distant metastasis. Conclusions. High lncRNA GHET1 expression can predict poor survival and pathological parameters. And lncRNA GHET1 could serve as a new indicator in multiple cancers.

Comparison of the clinical outcomes and prognostic factors of dedifferentiated chondrosarcoma and chondroblastic osteosarcoma: a population-based analysis

Background Dedifferentiated chondrosarcoma (DDC) and chondroblastic osteosarcoma (COS) have some common morphological characteristics by pathology and involve the same surgical methods and chemotherapy regimen. We explored the prognostic differences and factors of patients with DDC and COS with similar pathological features to analyze the prognostic factors and effect of chemotherapy on the prognosis of each type. Methods From the SEER database, we included 228 patients with DDC and 631 patients with COS who underwent surgery from 1975 to 2016. Patient age was stratified with X-tile, and prognosis was analyzed by the Kaplan-Meier method and Cox proportional hazard regression. Results The 3- and 5-year overall survival (OS) rates for DDC were 33.3% and 26.5%, respectively, and the 3- and 5-year OS rates for COS were 71.5% and 63.8%, respectively. Compared with COS, DDC had an older onset age, a higher proportion of white patients, an increased likelihood of occurrence in soft tissue, a higher pathological grade, a larger tumor volume, more patients with M1-stage, a higher AJCC stage and a lower chemotherapy utilization rate. Univariate analysis showed that age, M1 stage and high tumor stage were negatively correlated with DDC patient prognosis, with a worse prognosis for patients with lung metastasis. In the multivariate analysis, higher tumor stage was an independent factor for reducing OS in DDC. Univariate analysis showed that COS patients were older and male; had tumors located in the pelvis; had high T-, M-, and AJCC-stage tumors; and had lung metastasis. Moreover, no chemotherapy was negatively correlated with patient prognosis. Furthermore, age, male sex and high tumor stage were independent factors for reducing OS in COS. Conclusion The OS of DDC patients is worse than that of COS patients. Chemotherapy cannot benefit patients with DDC. For COS patients, further exploration of the survival benefits of chemotherapy is needed.

Significance of lncRNA MIR31HG in predicting the prognosis for Chinese patients with cancer: a meta-analysis

It is important to clarify the significance of long noncoding RNA MIR31 host gene (lncRNA MIR31HG) in predicting the prognosis for malignant tumors through meta-analysis. Electronic databases were systemically searched, from inception until 2 January 2019, to identify related articles. Meanwhile, the hazard ratios (odds ratios) and 95% CIs were computed for exploring the association between the expression of lncRNA MIR31HG and the survival (pathological variables). Eleven studies with 1041 cases were enrolled into the current meta-analysis. Low expression of lncRNA MIR31HG showed correlation with the dismal overall survival, disease-free survival, high tumor stage and lymph node metastasis among patients with digestive system cancers. Low expression of lncRNA MIR31HG may serve as a potential novel factor to indicate the dismal prognosis and metastasis in patients with digestive system cancers.

DUSP10 Is a Regulator of YAP1 Activity Promoting Cell Proliferation and Colorectal Cancer Progression

Cell contact inhibition (CCI) is deregulated in cancer. Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. We found that dual-specificity phosphatase 10 (DUSP10) is involved in CRC. DUSP10 overexpression increased the growth of CRC cell lines and mouse xenografts, while the opposite phenotype was observed by DUSP10 silencing. High cell density (HD) induced DUSP10 expression in CRC cell lines, particularly within the nucleus. Yes-associated protein 1 (YAP1) is activated by dephosphorylation, controlling organ growth and CCI, both processes being deregulated in CRC. Expression levels and localization of DUSP10 matched with YAP1 levels in CRC cell lines. DUSP10 and YAP1 co-immunoprecipitated and their interaction was dependent on YAP1 Ser397. The existence of DUSP10 and YAP1 pathway in vivo was confirmed by using a transgenic Drosophila model. Finally, in CRC patients’ samples, high levels of nuclear DUSP10 correlated with nuclear YAP1 in epithelial tumor tissue. Strong nuclear DUSP10 staining also correlated with high tumor stage and poor survival. Overall, these findings describe a DUSP10–YAP1 molecular link in CRC cell lines promoting cell growth in HD. We present evidence suggesting a pro-tumorigenic role of nuclear DUSP10 expression in CRC patients.

High Apelin Level Indicates a Poor Prognostic Factor in Muscle-Invasive Bladder Cancer

Purpose. To compare the expression level of apelin in muscle-invasive bladder cancer and matched paracarcinoma tissues and investigate the relationship between apelin and clinical prognosis in the patients. Methods. To assess apelin expression by using immunohistochemical method compared with bladder tumors and matched paracarcinoma tissues. Subsequently, the correlation of apelin expression with the clinicopathological features of bladder cancer patients was analyzed. Kaplan-Meier survival curves method was used to analyze apelin prognostic significance for muscle-invasive bladder cancer patients (including 404 muscle-invasive bladder cancer patients and 28 normal bladder tissues, in TCGA dataset). Results. Apelin protein level was overexpressed in bladder tumor tissues compared with paracarcinoma tissues. Furthermore, high apelin expression was associated with high tumor stage (P<0.05), distant metastasis (P<0.05), and vascular invasion (P<0.05). Kaplan-Meier curve analyses showed that the overexpression of apelin was a potential predictor of overall survival and disease-free survival. Conclusion. Apelin was upregulated in bladder tumor tissues compared with matched adjacent noncancer tissues, especially in the high tumor stage, distant metastasis, and vascular invasion. What is more, high expression of apelin in muscle-invasive bladder cancer indicates the poor prognosis. These data suggested that apelin might be a therapeutic potential biomarker in muscle-invasive bladder cancer patients.

Role of ARPC2 in Human Gastric Cancer

Gastric cancer continues to be the second most frequent cause of cancer deaths worldwide. However, the exact molecular mechanisms are still unclear. Further research to find potential targets for therapy is critical and urgent. In this study, we found that ARPC2 promoted cell proliferation and invasion in the human cancer cell line MKN-28 using a cell total number assay, MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay, cell colony formation assay, migration assay, invasion assay, and wound healing assay. For downstream pathways, CTNND1, EZH2, BCL2L2, CDH2, VIM, and EGFR were upregulated by ARPC2, whereas PTEN, BAK, and CDH1 were downregulated by ARPC2. In a clinical study, we examined the expression of ARPC2 in 110 cases of normal human gastric tissues and 110 cases of human gastric cancer tissues. ARPC2 showed higher expression in gastric cancer tissues than in normal gastric tissues. In the association analysis of 110 gastric cancer tissues, ARPC2 showed significant associations with large tumor size, lymph node invasion, and high tumor stage. In addition, ARPC2-positive patients exhibited lower RFS and OS rates compared with ARPC2-negative patients. We thus identify that ARPC2 plays an aneretic role in human gastric cancer and provided a new target for gastric cancer therapy.