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2021 ◽  
Author(s):  
Yue Qi ◽  
Yue Wang

Abstract Background: This study aimed to explore the expression of Family with sequence similarity 83 (FAM83) members in cervical cancer, its prognostic value, related signaling pathways, regulatory mechanisms, and immune infiltration. It’s of great value to explore the potential role of FAM83 family in cervical cancer and provide a new scientific basis for targeted therapy.Methods: The expression, gene mutations and prognostic value of FAM83 family members in cervical cancer were analyzed by various bioinformatics tools and databases. We further explored the interaction regulation network and immune infiltration between FAM83 family members and their closely related genes through a series of databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathways (KEGG) enrichment were also conducted.Results: This study showed that the expression levels of FAM83A/B/C/D/E/F/G/H gene were upregulated in cervical cancer, the expression of FAM83B/C/D/E/F/G/H were related to tumor stages of cervical cancer, and the promoter methylation of FAM83A/D/E/F/G genes in cervical cancer were lower than those in normal tissues. What’s more, high expression of FAM83A, FAM83B, and FAM83H mRNA was associated with shortened overall survival. GO results showed that FAM83A, FAM83B, and FAM83H and their closely related genes can play an important role in cell-cell junction, calcium-dependent protein binding, regulation of peptidase activity, inflammatory response. KEGG analysis results showed that FAM83A, FAM83B, and FAM83H and their closely related genes were significantly enriched in cancer pathways, estrogen signaling pathway, MAPK signaling pathway. Furthermore, FAM83A, FAM83B, and FAM83H are all closely related to lymphocytes (Tcm_CD4, Tcm_CD8, and neutrophils) and immunomodulators (TGFBR1, TGFB1, and TNFSF9).Conclusions: With multiple databases, we found that the high expression of FAM83A, FAM83B, and FAM83H were associated with the shortened survival time and poor prognosis in patients with cervical cancer, and also closely correlated with lymphocytes and immune infiltration, suggesting that FAM83A, FAM83B, and FAM83H played an important role in the occurrence, development, malignant biological behavior, and immune infilatration of cervical cancer, which provides an important theoretical basis for early diagnosis and targeted therapy for cervical cancer.


Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3838
Author(s):  
Mousumi Majumder ◽  
Kingsley Chukwunonso Ugwuagbo ◽  
Sujit Maiti ◽  
Peeyush K Lala ◽  
Muriel Brackstone

We reported that two microRNAs, miR526b and miR655, are oncogenic in breast cancer (BC). Overexpression of these two miRNAs in poorly metastatic BC cells promotes aggressive BC phenotypes in vitro and in vivo. High expression of each miRNA was associated with poor patient survival. In this pilot biomarker study, we report for the first time that miRNA precursor RNAs (pri-miRNAs) are robust and sensitive biomarkers for BC, detectable in both human blood plasma and biopsy tissues. Pri-miRNA detection and quantification do not require a special enrichment procedure, thus reducing specimen quantity. Blood plasma samples from 90 malignant tumor-bearing patients and 20 benign lesion-bearing participants (control) were analyzed for pri-miRNA expression with a quantitative real-time polymerase chain reaction. Results revealed that normalized expressions of plasma pri-miR526b and pri-miR655 are significantly upregulated in malignancy compared to benign plasmas (p = 0.002 and p = 0.03, respectively). Both pri-miRNAs showed more prominent results to distinguish stage I plasmas from benign plasmas (p = 0.001 for pri-miR526b and p = 0.0001 for pri-miR655). We have also validated pri-miRNA expression in independent tumor bank tissues, showing significant upregulation of both pri-miRNAs in BC; thus, pri-miRNAs are robust markers. The diagnostic relevance of pri-miRNAs was computed with the area under the curve (AUC). Pri-miR526b is a sensitive biomarker to distinguish cancer from control plasmas (sensitivity of 86%; AUC = 71.47%, p = 0.0027) with a positive predictive value of 88.89%; however, pri-miR655 did not show significant sensitivity. Furthermore, pri-miR526b could also significantly distinguish tumors as early as stage I from control (sensitivity of 75%; AUC = 72.71%, p = 0.0037). Therefore, pri-miR526b can be used as an early diagnostic biomarker. The expression of both pri-miRNAs was significantly high in ER-positive and HER2-negative subgroups of BC; hence, these biomarkers might play a role in the management of endocrine therapy designs. Additionally, with a case–control cohort study, we identified that high expression of pri-miR526b in the blood is also a risk factor associated with breast cancer (OR = 4.3, CI = 1.39–13.34, p = 0.01). Pri-miRNAs could be considered novel breast cancer blood biomarkers.


2021 ◽  
Author(s):  
Chaowen He ◽  
Dongxuan Huang ◽  
Fan Yang ◽  
Dongsheng Huang ◽  
Yahui Cao ◽  
...  

Abstract Objective: This study aims to investigate the expression and clinical value of long non-coding RNA (lncRNA) HEIH in peripheral blood of patients with non-small cell lung cancer (NSCLC).Methods: Healthy subjects (N=70), patients with lung squamous cell carcinoma (LUSC, N=70) and patients with lung adenocarcinoma (LUAD, N=80) were included. LncRNA HEIH expression in peripheral blood of included subjects was detected. According to the median expression of lncRNA HEIH, LUSC and LUAD patients were divided into lncRNA HEIH high/low expression group. The correlation between lncRNA HEIH and clinical indicators of patients was analyzed. Receiver-operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of lncRNA HEIH and carcinoembryonic antigen (CEA) in LUSC and LUAD patients. MedCalc-Comparison of ROC curves was used to compare the area under ROC curve. The cumulative survival rates of lncRNA HEIH high/low expression group were analyzed by Kaplan-Meier curve.Results: LncRNA HEIH in peripheral blood of LUSC and LUAD patients was higher than that in healthy controls, with no evident difference between LUSC and LUAD groups. LUSC and LUAD patients with high lncRNA HEIH expression had larger tumor size, higher CEA level and tumor stage, and higher risk of lymph node metastasis and distal metastasis. LncRNA HEIH had higher diagnostic efficiency than CEA in NSCLC patients. High expression of lncRNA HEIH predicted poor prognosis in patients with NSCLC.Conclusions: High expression of lncRNA HEIH is helpful in the diagnosis of NSCLC and predicts poor prognosis.


2021 ◽  
Author(s):  
Xue He ◽  
Weilong Zhang ◽  
Wei Fu ◽  
Xiaoni Liu ◽  
Ping Yang ◽  
...  

Abstract Background Acute myeloid leukemia (AML) is a significantly heterogeneous malignancy of the blood. Cytogenetic abnormalities are crucial for the prognosis of AML. However, since more than half of patients with AML are cytogenetically normal AML (CN-AML), new markers are badly required for predicting prognosis. In recent years, gene abnormalities are considered to be strong prognostic factors of CN-AML, already having clinical significance for treatment. In addition, the relationship of methylation in some genes and AML prognosis predicting has been discovered. RASGEF1A is a guanine nucleotide exchange factors of Ras, and has been reported to relate to malignancy. However, there is no research about the relationship of RASGEF1A gene and CN-AML. Methods By integrating the Cancer Genome Atlas (TCGA) database 75 patients with CN-AML and 240 Gene Expression Omnibus (GEO) database CN-AML samples, we examined the association between RASGEF1A ’s RNA expression level and DNA methylation of and AML patients’ prognosis. Then, we investigated the RASGEF1A RNA expression and DNA methylation’s prognostic value in 77 patients with AML after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) as well as 101 AML patients after chemotherapy respectively. We investigated the association between sensitivity to Crenolanib and expression level of RASGED1A in patients by integrating 191 CN-AML patients from BeatAML dadataset. Finally, we integrated the expression and methylation of RASGEF1A to predict the CN-AML patients’ prognosis. Results We found that RASGEF1A gene high expression group predicted poorer event-free survival (EFS) (P < 0.0001) as well as overall survival (OS) (P < 0.0001) in CN-AML samples, and the identical results were found in AML patients receiving chemotherapy (P < 0.0001) and Allo-HSCT (P < 0.0001). RASGEF1A RNA expression level is an CN-AML patients’ independent prognostic factor (EFS: HR = 5.5534, 95% CI: 1.2982–23.756, P = 0.0208; OS: HR = 5.3615, 95% CI: 1.1014–26.099, P = 0.0376). The IC50 (half maximal inhibitory concentration) of Crenolanib of CN-AML samples with RASGEF1A high expression level is lower. In addition, patients with high RASGEF1A methylation level had significant favorable prognosis (EPS: P < 0.0001, OS: P < 0.0001). Furthermore, the integrative analysis of expression and methylation of RASGEF1A could classify CN-AML patients into subgroups with different prognosis (EFS: P < 0.0001, OS: P < 0.0001). Conclusion Higher RASGEF1A RNA expression and lower DNA methylation predicts CN-AML patients’ poorer prognosis. The RASGEF1A high expression level from patients with CN-AML have better sensitivity to Crenolanib. The integrative analysis of RASGEF1A RNA expression and DNA methylation can provide a more accurate classification for prognosis. Lower RASGEF1A expression is a favorable prognostic factor for AML patients receiving chemotherapy or Allo-HSCT.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maiko Uehara ◽  
Eri Tabata ◽  
Mikoto Okuda ◽  
Yukari Maruyama ◽  
Vaclav Matoska ◽  
...  

AbstractDiet of the crab-eating monkey (Macaca fascicularis) consists of both plants and animals, including chitin-containing organisms such as crabs and insects. This omnivorous monkey has a high expression of acidic chitinase (CHIA) in the stomach and here, we report on its enzymatic properties under different conditions. When we compared with Mus musculus CHIA (Mm-CHIA), Macaca fascicularis CHIA (Mf-CHIA) exhibits higher chitinolytic activity at broad pH (1.0–7.0) and temperature (30–70 ℃) range. Interestingly, at its optimum pH (5.0), Mf-CHIA showed the highest activity at 65 °C while maintaining it at robust levels between 50 and 70 °C. The degradation efficiency of Mf-CHIA was superior to Mm-CHIA toward both polymeric chitin as well as an artificial chromogenic substrate. Our results show that unique features of Mf-CHIA including its thermostability warrant the nomination of this enzyme for potential agricultural and biomedical applications.


2021 ◽  
Author(s):  
Mengjun Zhang ◽  
Yue Yin ◽  
Zhenxing Sun ◽  
Yuan Liu ◽  
Yiru Wang ◽  
...  

Abstract Background: Ovarian cancer (OV) is one of the most common gynecological malignancies worldwide, and its immunotherapy has considerable prospects. Multiple members of the CMTM family were aberrantly expressed in human cancers and controled key malignant biological processes and immune regulation in cancer development. However, little is known about the function of this gene family in ovarian cancer, especially in terms of immunity.Methods: GEPIA, Oncomine, HPA, Kaplan-Meier plotter, cBioPortal, GeneMANIA and TIMER were used to analyze the differential gene expression, prognostic value, genetic alterations and alterations in the immune microenvironment of the CMTM family in patients with ovarian cancer. Importantly, RT-qPCR was used to verify the gene expression of the CMTM family.Results: CMTM1/3/4/6/7/8 showed abnormally high expression at the mRNA and protein levels in OV tissues based on the GEPIA and HPA databases. RT-qPCR showed that CMTM1/6/8 was highly expressed in ovarian cancer cell lines. Survival analysis showed that high expression of CMTM1/2/3/5/8 can lead to a significant reduction in overall survival and progression-free survival. There were many types of genetic alterations in the CMTM family. And CMTM1/2/3/6 had a certain correlation with the changes of immune microenvironment such as immune cell infiltration and immune checkpoint expression, which may be the potential mechanism of the CMTM family in ovarian cancer.Conclusion: This study confirmed that the CMTM family has abnormal expression in ovarian cancer and can be used as a biomarker for prognostic evaluation. And the CMTM family may be used as a potential target for immunotherapy based on the suppression of immune checkpoints.


Author(s):  
Ning Sun ◽  
Chenchen Li ◽  
Yue Teng ◽  
Yuxia Deng ◽  
Lin Shi

Background: Breast cancer is a common malignant tumor, threatening the general health of women worldwide. Estrogen-related receptor alpha (ERRα) is a member of nuclear receptor family and has been shown to involve in the pathophysiology of breast cancer. However, the specific relationship between ERRα and the triple negative breast cancer (TNBC), is not clear yet. Objective: This study examined the relevance between ERRα expression and different clinical features of breast cancer patients. Methods: The expression level of ERRα in 150 human breast cancer tissues (which contains 48 human triple negative breast cancer tissues) and 53 human benign breast tumor tissues using immunohistochemical staining. Results: ERRα protein level was significantly higher in breast cancer tissues than that in benign tumors. High expression of ERRα was significantly associated with the high grade but not the clinical stage and human epidermal growth factor receptor 2 of the breast cancer tissues. Its high expression was also positively correlated with triple negative breast cancer in pathological grade 2 and 3, but not in grade 1. high expression of ERRα was positively correlated with triple negative breast cancer in each clinical stage. In addition, high expression of ERRα was associated with shorter overall survival of breast cancer patients. Conclusion: In conclusion, highly expressed ERRα was associated with higher pathological grades triple-negative breast cancer and shorter overall survival. Future studies were required to recruit more patients to consolidate the current findings.


Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3793
Author(s):  
Katyana Amilca-Seba ◽  
Michèle Sabbah ◽  
Annette K. Larsen ◽  
Jérôme A. Denis

A high expression of the phosphoprotein osteopontin (OPN) has been associated with cancer progression in several tumor types, including breast cancer, hepatocarcinoma, ovarian cancer, and colorectal cancer (CRC). Interestingly, OPN is overexpressed in CRC and is associated with a poor prognosis linked to invasion and metastasis. Here, we review the regulation and functions of OPN with an emphasis on CRC. We examine how epigenetic and genetic regulators interact with the key signaling pathways involved in this disease. Then, we describe the role of OPN in cancer progression, including proliferation, survival, migration, invasion, and angiogenesis. Furthermore, we outline the interest of using OPN as a clinical biomarker, and discuss if and how osteopontin can be implemented as a routine assay in clinical laboratories for monitoring CRC patients. Finally, we discuss the use of OPN an attractive, but challenging, therapeutic target.


Author(s):  
Guillaume Giraud ◽  
Rachel Paul ◽  
Marilyne Duffraisse ◽  
Soumen Khan ◽  
L. S. Shashidhara ◽  
...  

Developmental processes have to be robust but also flexible enough to respond to genetic and environmental variations. Different mechanisms have been described to explain the apparent antagonistic nature of developmental robustness and plasticity. Here, we present a “self-sufficient” molecular model to explain the development of a particular flight organ that is under the control of the Hox gene Ultrabithorax (Ubx) in the fruit fly Drosophila melanogaster. Our model is based on a candidate RNAi screen and additional genetic analyses that all converge to an autonomous and cofactor-independent mode of action for Ubx. We postulate that this self-sufficient molecular mechanism is possible due to an unusually high expression level of the Hox protein. We propose that high dosage could constitute a so far poorly investigated molecular strategy for allowing Hox proteins to both innovate and stabilize new forms during evolution.


Author(s):  
Hamidreza Mosleh ◽  
Fatemeh Moradi ◽  
Mehdi Mehdizadeh ◽  
Marziyeh Ajdary ◽  
Alaa Moeinzadeh ◽  
...  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus found in China in 2019. The disease caused by SARS-CoV-2, coronavirus disease 2019 (COVID-19), has been found to be closely related to the cells that secrete angiotensin-converting enzyme 2 (ACE2). ACE2 is involved in the renin-angiotensin system and is widely secreted in several tissues, including the testis, which has raised concerns because organs with high expression of the ACE2 receptor are susceptible to infection. Analyses have shown that in testicular cells, such as spermatogonia, seminiferous duct cells, Sertoli cells, and Leydig cells, there is a high expression level of ACE2. Therefore, SARS-CoV-2 may damage male reproductive tissues and cause infertility. Since male infertility is an important problem, scientists are evaluating whether COVID-19 may influence male infertility through the ACE2 receptor.


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