Dynamics of Microbiome Changes in the Endometrium and Uterine Cervix during Embryo Implantation: A Comparative Analysis.

BACKGROUND The microbiome is the collection of all micro-organisms and their genes, which naturally live in and on the body. The cervical and endometrial bacterial microbiome has previously been reported to affect fertility and influence the outcomes of assisted reproductive therapy (ART), including embryo transfer. This study aimed to evaluate the cervical and endometrial bacterial microbiome in 177 women treated for infertility before, during, and after embryo implantation, and the outcomes. MATERIAL AND METHODS Cervical and endometrial swabs were collected from 177 women diagnosed with infertility at 3 time points: (1) during the initial examination, (2) during implantation, (3) 10-14 days after implantation. Next-generation sequencing (NGS) was used to analyze the bacterial microbiome. Taxonomic identification was performed with the Usearch algorithm. RESULTS There was a significant change in the number of patients with Escherichia coli depending on the collection time. For the first swab collection, there were significant negative relationships between the percentage of Gardnerella vaginalis and Lactobacillus spp. For the second collection, there was a negative relationship between Lactobacillus helveticus and Lactobacillus jensenii. For the third collection, negative relationships were found between Escherichia coli and Lactobacillus spp. A similar distribution of the bacterial microbiome was observed in all 3 swab collections. CONCLUSIONS Lactobacillus spp. were the main bacteria identified in the cervix and endometrium, present before, during, and after successful embryo transfer. E. coli and G. vaginalis reduced the protective effect of Lactobacilli before, during, and after embryo transfer.

The influence of selected microRNAs on the expression profile of genes and proteins related to the tumor necrosis factor-alpha signaling pathways in endometrioid endometrial cancer.

PURPOSE: Tumor necrosis factor exerts many adverse biological effects, from cell proliferation to cell death. Accurate diagnosis and treatment are therefore difficult due to many factors influencing tumor necrosis factor-alpha (TNF-α) signaling, including microRNAs (miRNAs), especially in tumors. The aim of the study was to determine the influence of miRNAs on the expression profile of genes and proteins related to TNF-α signaling in endometrial cancer. METHODS: The material consisted of 45 endometrioid endometrial cancer and 45 normal endometrium tissue samples. Gene expression was determined with microarrays and then validated for TNF-α, tumor necrosis factor receptor 1 (TNFR1) and 2 (TNFR2), caveolin 1 (CAV1), nuclear factor kappa B subunit 1 (NFKB1), and TGF-beta activated kinase 1 (MAP3K7)-binding protein 2 (TAB2) using real-time quantitative reverse transcription reaction (RT-qPCR). The protein concentration was assessed by enzyme-linked immunosorbent assay (ELISA). In addition, differentiating miRNAs were identified using miRNA microarrays and their relationships with TNF-α signaling genes were evaluated using the mirDIP tool. RESULTS: TNF-α, TNFR1, TNFR2, CAV1, NFKB1, and TAB2 were upregulated both on the mRNA and protein levels. The decrease in the activity of miR-1207-5p, miR-1910-3p, and miR-940 may be related to CAV1 overexpression. Similarly for miR-572 and NFKB1 as well as miR-939-5p and TNF-α. In turn, miR-3178 may partially inhibit TNFR1 activity up to grade 2 cancer. CONCLUSION: TNF-α signaling, especially the TNF-α/NF-κB axis, is disrupted in endometrial cancer and worsens with disease progression. The observed changes may be the result of miRNAs' activity in the initial stage of endometrial cancer and its gradual loss in later grades.

Detection and Genotyping of Human Papillomavirus (HPV16/18), Epstein-Barr Virus (EBV), and Human Cytomegalovirus (HCMV) in Endometrial Endometroid and Ovarian Cancers.

The purpose of this study was to evaluate the relationship between human papillomavirus (HPV16/18), Epstein-Barr virus (EBV), and human cytomegalovirus (HCMV) infections and the occurrence of ovarian cancer in 48 women, of whom 36 underwent surgery and chemotherapy (group A), 12 in whom surgery was sufficient (group B), and 60 with endometroid endometrial cancer stage G1-G3 (group C), compared to patients in whom the uterus and its appendages were removed for nononcological reasons (control group). The detection of HPV, EBV, and HCMV in tumor tissue and normal tissue was performed using the real-time polymerase chain reaction (RT-PCR) technique. A statistically significantly higher risk of endometrial cancer was noted in patients infected only with HCMV (OR > 1; p < 0.05). In contrast, a significantly higher risk of ovarian cancer in group A was associated with HPV16, HPV18, and EBV (OR > 1; p < 0.05); a significantly higher risk of ovarian cancer in group B was associated with HPV18 and HMCV (OR > 1; p < 0.05). The obtained results suggest that HCMV infection is associated with the development of a stage of ovarian cancer when treatment can be completed with surgery alone. Meanwhile, EBV appears to be responsible for the development of ovarian cancer in more advanced stages.

Endothelin-3 is epigenetically silenced in endometrioid endometrial cancer.

PURPOSE: Changes in the activity of endothelins and their receptors may promote neoplastic processes. They can be caused by epigenetic modifications and modulators, but little is known about endothelin-3 (EDN3), particularly in endometrial cancer. The aim of the study was to determine the expression profile of endothelin family and their interactions with miRNAs, and to assess the degree of EDN3 methylation. METHODS: The study enrolled 45 patients with endometrioid endometrial cancer and 30 patients without neoplastic changes. The expression profile of endothelins and their receptors was determined with mRNA microarrays and RT-qPCR. The miRNA prediction was based on the miRNA microarray experiment and the mirDB tool. The degree of EDN3 methylation was assessed by MSP. RESULTS: EDN1 and EDNRA were overexpressed regardless of endometrial cancer grade, which may be due to the lack of regulatory effect of miR-130a-3p and miR-485-3p, respectively. In addition, EDN3 and EDNRB were significantly downregulated. CONCLUSION: The endothelial axis is disturbed in endometrioid endometrial cancer. The observed silencing of EDN3 activity may be mainly due to DNA methylation.

miRNAs Participate in the Regulation of Oxidative Stress-Related Gene Expression in Endometrioid Endometrial Cancer.

Reactive oxygen species are formed as by-products of normal cell metabolism. They are needed to maintain cell homeostasis and signaling, which is possible due to defense systems. Disruption of this balance leads to oxidative stress that can induce cancer. Redox regulation by miRNAs may be a potential therapeutic target. The aim of the study was to assess the activity of genes associated with oxidative stress in endometrial cancer and to determine their relationship with miRNAs. The study included 45 patients with endometrioid endometrial cancer and 45 without neoplastic changes. The expression profile of genes associated with oxidative stress was determined with mRNA microarrays, RT-qPCR and ELISA. The miRNA prediction was performed based on the miRNA microarray experiment and the mirDB tool. PRDX2 and AQP1 showed overexpression that was probably not related to miRNA activity. A high level of PKD2 may be the result of a decrease in the activity of miR-195-3p, miR-20a, miR-134. A SOD3 level reduction can be caused by miR-328, miR-363. In addition, miR-363 can also regulate KLF2 expression. In the course of endometrial cancer, the phenomenon of oxidative stress is observed, the regulation of which may be influenced by miRNAs.

Trichopsychodermatology: trichotillomania and trichophagia leading to Rapunzel syndrome.

Introduction: The Rapunzel syndrome occurs when the trichobezoar (hair ball) extends beyond the small intestine and sometimes even into the colon, producing long, tail-like hair extensions. Aim: To present cases of trichobezoars, an extremely rare human intestinal disease caused by the ingestion of hair (trichophagia). Material and methods: In this retrospective study, we assessed the medical records of 2 patients diagnosed with Rapunzel syndrome admitted to Academic Clinical Hospital No. 2 in Rzeszow, Poland. Results: The first patient was a 15-year-old girl. The abdominal ultrasound examination revealed an abnormal, non-compressible structure with the approximate dimensions of 12 × 11 cm in the epigastrium, with a strong shadow obscuring the view. Gastroscopy was performed and a tumour sample was taken for histopathological examination, which confirmed the diagnosis of a trichobezoar. The patient's mother did not agree to her daughter's psychiatric treatment. The second patient was a 15-year-old girl who reported to the Emergency Room in critical condition due to dehydration and long-term emesis with symptoms of cachexia. Ileotomy with the removal of two trichobezoars with a diameter of about 5 cm and 7 cm was performed. The patient was discharged for treatment at the Mental Health Clinic for trichotillomania. Conclusions: Trichobezoars give non-specific symptoms that may imitate other diseases for example tumours. Psychotherapy is the recommended treatment and follow-up visits are important in preventing relapses.

Clinical and molecular evaluation of patients with ovarian cancer in the context of drug resistance to chemotherapy.

The present study aimed to evaluate changes in the expression patterns at the gene and protein levels associated with drug resistance. The study group included 48 women who had a histopathologically confirmed diagnosis of stage I-IV ovarian cancer, they were divided into two subgroups (groups A and B). In group A, there were 36 patients in whom surgical treatment was supplemented with first-line chemotherapy according to current standards. Within this patient group, 5 had stage I (14%), 5 had stage II (14%), 25 had stage III (69%), and 1 had stage IV ovarian cancer (3%). Drug resistance was found after the third cycle of chemotherapy in 17 patients (71%) and after the sixth cycle in 7 patients (29%). Group B included 12 women with type I ovarian cancer, including 11 with stage I and 1 patient with stage IV ovarian cancer. The oncological treatment required only surgery. The control group (C) included 50 women in whom the uterus and adnexa were surgically removed for non-oncological reasons. Significantly higher levels of carcinoma antigen 125 CA-125 and human epididymis protein 4 HE4 were observed in group A and in menopausal women. Moreover, drug resistance was associated with significantly higher levels of CA-125 (p < 0.05). The genes UBA2, GLO1, STATH, and TUFT1 were differentiated in test samples from control samples. Moreover, drug resistance was associated with significantly higher expression of GLO1. The results of these assessments indicated the strong link between UBA2 and hsa-miR-133a-3p and hsa-miR-133b; GLO1 and hsa-miR-561-5p; STATH and hsa-miR-137-3p and hsa-miR-580-3p; and TUFT1 and hsa-miR-1233-3p and hsa-miR-2052. Correlation analysis showed a significant correlation between CA-125 and HE4 levels. Moreover, a significant correlation between TUFT1 mRNA and UBA2, GLO1, STATH (negative correlation), and TUFT1 in relation to CA-125 and HE4 (p < 0.05) was noted in all patients. In view of the lack of screening tests for ovarian cancer, the occurrence of the described correlation may be inscribed as an attempt to establish an assay that meets the criteria of a screening test and thus increase the early diagnosis of ovarian cancer.

Epigenetic regulation of autophagy in gastrointestinal cancers.

The development of novel therapeutic approaches is necessary to manage gastrointestinal cancers (GICs). Considering the effective molecular mechanisms involved in tumor growth, the therapeutic response is pivotal in this process. Autophagy is a highly conserved catabolic process that acts as a double-edged sword in tumorigenesis and tumor inhibition in a context-dependent manner. Depending on the stage of malignancy and cellular origin of the tumor, autophagy might result in cancer cell survival or death during the GICs' progression. Moreover, autophagy can prevent the progression of GIC in the early stages but leads to chemoresistance in advanced stages. Therefore, targeting specific arms of autophagy could be a promising strategy in the prevention of chemoresistance and treatment of GIC. It has been revealed that autophagy is a cytoplasmic event that is subject to transcriptional and epigenetic regulation inside the nucleus. The effect of epigenetic regulation (including DNA methylation, histone modification, and expression of non-coding RNAs (ncRNAs) in cellular fate is still not completely understood. Recent findings have indicated that epigenetic alterations can modify several genes and modulators, eventually leading to inhibition or promotion of autophagy in different cancer stages, and mediating chemoresistance or chemosensitivity. The current review focuses on the links between autophagy and epigenetics in GICs and discusses: 1) How autophagy and epigenetics are linked in GICs, by considering different epigenetic mechanisms; 2) how epigenetics may be involved in the alteration of cancer-related phenotypes, including cell proliferation, invasion, and migration; and 3) how epidrugs modulate autophagy in GICs to overcome chemoresistance.

Cutaneous metastasis as the first sign of renal cell carcinoma - crossroad between literature analysis and own observations.

Introduction: Metastatic disease can be observed in nearly 25% of all renal cell carcinoma cases (RCC). This can present in the skin as a late symptom of the disease or as a manifestation of an undetected, asymptomatic RCC. Aim: To review the literature and present a case study of cutaneous metastasis in primary genitourinary malignancy, especially RCC in order to broaden the related knowledge. Material and methods: The first stage of our work was focused on presenting the results of the literature review about cutaneous metastasis in the patients with renal cell carcinoma. Next, taking into account that this type of metastasis associated with RCC is relatively rare, we have decided to present a patient aged 68 with incidentally detected skin metastases of RCC located on the scalp. Results: It was diagnosed as a primary manifestation of advanced disease. Computed tomography scans showed a solid mass in the left kidney. Following surgical excision of the skin lesion, a left-side nephrectomy was performed. Conclusions: Cutaneous metastases of RCC present an unfavourable prognosis, however, remission is possible subsequent to early diagnosis and appropriate surgical excision.

Marking the Profile of the Microflora of the Endometrium and Uterine Cervix in Women as a Potential Factor Determining the Effectiveness of In Vitro Fertilization.

One promising research trend involves evaluating the influence of microbiota in the reproductive system of women on becoming pregnant and maintaining pregnancy. The goal of this study was to define the microflora profile of the endometrium and uterine cervix in women qualified for an in vitro fertilization (IVF) procedure, which is expected to contribute to increasing the percentage of successful IVF implantations. Based on the conducted molecular analysis in the collected swabs, 22 bacterial strains were identified. Eleven strains (57%) that were isolated belong to the physiological microflora, the most common strain of which was Lactobacillus. Eight of the isolated strains (33%) were pathological microflora, among which the most common bacteria were from the Enterobacteriaceae family (which includes E. coli, Shigella, and Salmonella). Finally, three of the bacterial strains (10%) may be a component of both physiological or pathological microflora of the vagina: Bifidobacterium breve, Bifidobacterium longum group, and Alloscardovia omnicolens. The presence of Escherichia coli was detected in six women, Staphylococcus aureus also in six patients, Atopobium parvulum in three, Streptococcus salivarius group in three, Enterococcus faecalis in four, and Aerococcus christensenii in two patients. We found statistically significant relationships (p < 0.05) between Lactobacillus fermentum and Enterococcus faecalis, Lactobacillus delbrueckii and Escherichia coli groups, Lactobacillus FN667084_s and Staphylococcus aureus groups, as well as Lactobacillus fermentum and Streptococcus agalactiae. Based on the conducted study, it may be confirmed that the endometrium is, to a large extent, colonized by lactic acid bacilli. Apart from that, endometrial dysbiosis was not noted in patients qualified for the IVF procedure.

Expression Profile of mRNAs and miRNAs Related to the Oxidative-Stress Phenomenon in the Ishikawa Cell Line Treated Either Cisplatin or Salinomycin.

The oxidative stress phenomenon is a result of anticancer therapy. The aim of this study was the assessment of gene expression profile changes, and to determine the miRNAs regulating genes' transcriptional activity in an Ishikawa endometrial cancer culture exposed to cisplatin or salinomycin, compared to a control culture. The molecular analysis comprised the microarray technique (mRNAs and micro RNA (miRNA), the real-time quantitative reverse transcription reaction (RTqPCR), enzyme-linked immunosorbent assay (ELISA) reactions, and Western blot. NR4A2, MAP3K8, ICAM1, IL21, CXCL8, CCL7, and SLC7A11 were statistically significantly differentiated depending not only on time, but also on the drug used in the experiment. The conducted assessment indicated that the strongest links were between NR4A2 and hsa-miR-30a-5p and has-miR-302e, MAP3K8 and hsa-miR-144-3p, CXCL8 and hsa-miR-140-3p, and SLC7A11 and hsa-miR-144-3p. The obtained results suggest that four mRNAs-NR4A2, MAP3K8, CXCL8 and SLC7A11-and four miRNAs-hsa-miR-30a-5p, hsa-miR-302e, hsa-miR-144-3p and hsa-miR-140-3-changed their expressions regardless of the chemotherapeutic agent used, which suggests the possibility of their use in monitoring the severity of oxidative stress in endometrial cancer. However, considering the results at both the mRNA and the protein level, it is most likely that the expressions of NR4A2, MAP3K8, CXCL8 and SLC7A11 are regulated by miRNA molecules as well as other epigenetic mechanisms.

The Impact of Surgical Treatment with Adjuvant Chemotherapy for Ovarian Cancer on Disorders in the Urinary System and Quality of Life in Women.

Ovarian cancer is the fourth-most-common cause of death among all malignant cancers in women in Poland. This study aimed to compare the functioning of the urinary system and quality of life in women in the 12-month period following the completion of surgery or adjuvant treatment for ovarian cancer, with patients who underwent a hysterectomy for non-oncological reasons (control group). The study group consisted of 50 patients diagnosed with stage I−III ovarian cancer. Among 38 patients with type II ovarian cancer (group A), surgery followed by first-line chemotherapy was performed. Within this group of patients, 20 had stage I ovarian cancer, while 18 had stage II ovarian cancer. The study was performed at least 6 months after the final chemotherapy cycle, with no clinical, marker or radiological recurrence determined. On the other hand, in 12 patients with stage I type I ovarian cancer, oncological treatment consisted of only surgery, without the need for adjuvant chemotherapy, due to the low stage of the lesions (group B). In turn, the control group consisted of 50 women who underwent uterine removal for non-oncological reasons (group C). The assessment of quality of life was conducted using the questionnaires: Satisfaction with Life Scale (SWLS); Incontinence Impact Questionnaire, short form (IIQ-7); Urogenital Distress Inventory (UDI-6); and the Sexual Satisfaction Scale for 3, 6, 9, and 12 months after the conclusion of oncological treatment. During the follow-up, a significant reduction in the quality of everyday life and sexual life was noted among patients with ovarian cancer, more pronounced in group B, compared to the control group (p < 0.05). The risk of urinary incontinence is independent of the treatment regimen chosen for ovarian cancer. It is necessary to consider comprehensive psychological care and sexual therapy in patients with ovarian cancer and their families.

Recent Multiomics Approaches in Endometrial Cancer.

Endometrial cancer is the most common gynecological cancers in developed countries. Many of the mechanisms involved in its initiation and progression remain unclear. Analysis providing comprehensive data on the genome, transcriptome, proteome, and epigenome could help in selecting molecular markers and targets in endometrial cancer. Multiomics approaches can reveal disturbances in multiple biological systems, giving a broader picture of the problem. However, they provide a large amount of data that require processing and further integration prior to analysis. There are several repositories of multiomics datasets, including endometrial cancer data, as well as portals allowing multiomics data analysis and visualization, including Oncomine, UALCAN, LinkedOmics, and miRDB. Multiomics approaches have also been applied in endometrial cancer research in order to identify novel molecular markers and therapeutic targets. This review describes in detail the latest findings on multiomics approaches in endometrial cancer.

Variances in the Expression Profile of the EMT-Related Genes in Endometrial Cancer Lines In Vitro Study.

BACKGROUND: The aim of the study was to evaluate the variances in the expression pattern of mRNAs and miRNAs related to the EMT in the Ishikawa (histological grade 1; G1), EC-1A (histological grade 2; G2), and KLE (histological grade 3; G3) cell cultures under cisplatin treatment. METHODS: Endometrial cancer cell lines were exposed to 75.22 mg (an average concentration of the drug used in patients with endometrial cancer) for 12.24 and 48 hours in comparison to the untreated cells (control). The molecular analysis included: extraction of total RNA, microarray analysis (mRNA and miRNA), RTqPCR, and the ELISA assay. RESULTS: Out of 226 mRNAs associated with the EMT, the number of mRNAs differentially expressed in endometrial cancer cell cultures treated with cisplatin compared to a control culture was as follows: Ishikawa line - 87 mRNAs; EC-1A - 84 mRNAs; KLE - 71 mRNAs (p<0.05). The greatest changes in the Ishikawa line treated with the drug compared to the control were noticed for mRNA STAT1 TGFß1, SMAD3, FOXO8, whereas in EC-1A they were mRNA TGFß1, BAMBI, SMAD4, and in KLE mRNA COL1A1, FOXO8, TGFß1. The analysis also showed that miR-106a, miR-30d, miR-300 are common for all cell lines used in this experiment. CONCLUSION: Cisplatin changes the expression profile of genes associated with EMT in endometrial cancer cell lines. It seems that the expression pattern of TGFß1 might be a promising, supplementary molecular marker of the effectiveness of cisplatin therapy. The analysis showed that miR-30d, miR-300, and miR-106a are involved in the regulation of the expression of EMT-related genes.

Endocrine disorders and fertility and pregnancy: An update.

It is estimated that more and more couples suffer from fertility and pregnancy maintenance disorders. It is associated with impaired androgen secretion, which is influenced by many factors, ranging from genetic to environmental. It is also important to remember that fertility disorders can also result from abnormal anatomy of the reproductive male and female organ (congenital uterine anomalies - septate, unicornuate, bicornuate uterus; acquired defects of the uterus structure - fibroids, polyps, hypertrophy), disturbed hormonal cycle and obstruction of the fallopian tubes resulting from the presence of adhesions due to inflammation, endometriosis, and surgery, abnormal rhythm of menstrual bleeding, the abnormal concentration of hormones. There are many relationships between the endocrine organs, leading to a chain reaction when one of them fails to function properly. Conditions in which the immune system is involved, including infections and autoimmune diseases, also affect fertility. The form of treatment depends on infertility duration and the patient's age. It includes ovulation stimulation with clomiphene citrate or gonadotropins, metformin use, and weight loss interventions. Since so many different factors affect fertility, it is important to correctly diagnose what is causing the problem and to modify the treatment regimen if necessary. This review describes disturbances in the hormone secretion of individual endocrine organs in the context of fertility and the maintenance of pregnancy.

Crosstalk between Statins and Cancer Prevention and Therapy: An Update.

The importance of statins in cancer has been discussed in many studies. They are known for their anticancer properties against solid tumors of the liver or lung, as well as diffuse cancers, such as multiple myeloma or leukemia. Currently, the most commonly used statins are simvastatin, rosuvastatin and atorvastatin. The anti-tumor activity of statins is largely related to their ability to induce apoptosis by targeting cancer cells with high selectivity. Statins are also involved in the regulation of the histone acetylation level, the disturbance of which can lead to abnormal activity of genes involved in the regulation of proliferation, differentiation and apoptosis. As a result, tumor growth and its invasion may be promoted, which is associated with a poor prognosis. High levels of histone deacetylases are observed in many cancers; therefore, one of the therapeutic strategies is to use their inhibitors. Combining statins with histone deacetylase inhibitors can induce a synergistic anticancer effect.

Evaluation of the Differences in the Expression of Biogenic Amine-Related mRNAs and Proteins in Endometrioid Endometrial Cancer.

Biogenic amines, such as adrenaline, noradrenaline, histamine, dopamine, and serotonin are important neurotransmitters that also regulate cell viability. Their detection and analysis are helpful in the diagnosis of many diseases, including cancer. The aim of this study was to determine the expression profile of the biogenic amine-related genes and proteins in endometrioid endometrial cancer compared to the control group. The material consisted of endometrial tissue samples and whole blood collected from 30 endometrioid endometrial cancer patients and 30 cancer-free patients. The gene expression was determined by the mRNA microarrays and validated by qRT-PCR. Protein levels were determined in the serum by the enzyme-linked immunosorbent assay (ELISA). Overexpression of histamine H1-H3 receptors and early growth response 1 and silencing of calmodulin, the histamine H4 receptor, and the dopamine D5 receptor have been reported in endometrioid endometrial cancer. The obtained results indicate disturbances in the signaling activated by histamine and dopamine receptors, which could potentially contribute to the progression of endometrioid endometrial cancer.

miRNAs in the Expression Regulation of Dopamine-Related Genes and Proteins in Endometrial Cancer.

Disruption of the dopaminergic system leads to many diseases, including cancer. Dopamine and its receptors are involved in the regulation of proliferation, cell death, invasion, and migration. Better understanding of the mechanisms involved in these processes could reveal new molecular markers and therapeutic targets. The aim of this study was to determine the expression profile of dopamine-related genes and proteins in endometrial cancer and to assess whether miRNAs are involved in its regulation. Sixty women were recruited for the study: 30 with endometrial cancer and 30 without cancer. The expression profiles of dopamine-related genes were determined in endometrial tissue samples using microarrays and qRT-PCR. Then, protein concentration was determined with the ELISA test. In the last step, miRNA detection was performed using microarrays. The matching of miRNAs to the studied genes was carried out using the TargetScan tool. The analysis showed DRD2 and DRD3 overexpression, with a reduction in DRD5 expression, which could be due to miR-15a-5p, miR-141-3p, miR-4640-5p, and miR-221-5p activity. High levels of OPRK1 and CXCL12, related to the activity of miR-124-3p.1 and miR-135b-5p, have also been reported. Low COMT expression was probably not associated with miRNA regulation in endometrial cancer.

Variances in the Expression of mRNAs and miRNAs Related to the Histaminergic System in Endometrioid Endometrial Cancer.

Research has indicated higher concentrations of histamine and polyamine in endometrioid tissue in comparison with healthy tissue. The aim of this study was to evaluate changes in the expression patterns of messenger RNA (mRNAs) and microRNA (miRNAs) related to the histaminergic system in endometrial samples and whole blood in women with endometrioid endometrial cancer. The study group consisted of 30 women with endometrioid endometrial cancer qualified for hysterectomy (G1 well-differentiated, 15 cases; G2 moderately differentiated, 8 cases; and G3 poorly differentiated, 7 cases). The control group included 30 women with no neoplastic changes during routine gynecological examinations. The molecular analysis consisted of the microarray analysis of mRNAs and miRNAs related to the histaminergic system, reverse-transcription quantitative polymerase chain reaction (RTqPCR), and enzyme-linked immunosorbent assay (ELISA). Out of 65 mRNAs connected with the histaminergic system, 10 differentiate the samples of tissue and blood obtained from patients with endometrioid endometrial cancer in comparison with the control group (p < 0.05). mRNA histamine receptor 1,3 (HRH1, HRH3), and solute carrier family 22 member 3 (SLC23A2) differentiating samples of endometrioid endometrial cancer independent of either G or control. The highest probability of interaction, based on the target score miRDB, between the selected miRNAs and mRNAs was found for the hybrids hsa-miR-1-3p and endothelin 1 (END1), hsa-miR-27a-5ß and SLC23A2. The selected mRNA and miRNA transcripts seem to be promising for molecularly targeted therapies in the context of endometrioid endometrial cancer.

Expression Pattern of Leptin and Its Receptors in Endometrioid Endometrial Cancer.

The identification of novel molecular markers and the development of cancer treatment strategies are very important as cancer incidence is still very high. Obesity can contribute to cancer progression, including endometrial cancer. Adipocytes secrete leptin, which, when at a high level, is associated with an increased risk of cancer. The aim of this study was to determine the expression profile of leptin-related genes in the endometrial tissue samples and whole blood of patients. The study material included tissue samples and whole blood collected from 30 patients with endometrial cancer and 30 without cancer. Microarrays were used to assess the expression profile of leptin-related genes. Then, the expression of leptin (LEP), leptin receptor (LEPR), leptin receptor overlapping transcript (LEPROT), and leptin receptor overlapping transcript-like 1 (LEPROTL1) was determined by the Real-Time Quantitative Reverse Transcription Reaction (RT-qPCR). The serum leptin concentration was evaluated using Enzyme-linked immunosorbent assay (ELISA). Leptin and its receptors were overexpressed both at the mRNA and protein levels. Furthermore, there were strong positive correlations between leptin levels and patient Body Mass Index (BMI). Elevated levels of leptin and its receptors may potentially contribute to the progression of endometrial cancer. These observations may be useful in designing endometrial cancer treatment strategies.