Hepatocyte nuclear factor-1-beta (HNF1B) is a transcription factor and putative biomarker of solid tumours. Recently, we have revealed a variety of HNF1B mRNA alternative splicing variants (ASVs) with unknown, but potentially regulatory, functions. The aim of our work was to quantify the most common variants and compare their expression in tumour and non-tumour tissues of the large intestine, prostate, and kidney. The HNF1B mRNA variants 3p, Δ7, Δ7-8, and Δ8 were expressed across all the analysed tissues in 28.2-33.5%, 1.5-2%, 0.8-1.7%, and 2.3-6.9% of overall HNF1B mRNA expression, respectively, and occurred individually or in combination. The quantitative changes of ASVs between tumour and non-tumour tissue were observed for the large intestine (3p, Δ7-8), prostate (3p), and kidney samples (Δ7). Decreased expression of the overall HNF1B mRNA in the large intestine and prostate cancer samples compared with the corresponding non-tumour samples was observed (p = 0.019 and p = 0.047, respectively). The decreased mRNA expression correlated with decreased protein expression in large intestine carcinomas (p < 0.001). The qualitative and quantitative pattern of the ASVs studied by droplet digital PCR was confirmed by next-generation sequencing, which suggests the significance of the NGS approach for further massive evaluation of the splicing patterns in a variety of genes.

• MeSH
• alternativní sestřih * MeSH
• hepatocytární jaderný faktor 1-beta genetika   metabolismus   MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádory genetika   metabolismus   MeSH
• polymerázová řetězová reakce MeSH
• protein - isoformy MeSH
• regulace genové exprese u nádorů MeSH
• retrospektivní studie MeSH
• RNA nádorová genetika   metabolismus   MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

• MeSH
• biomechanika MeSH
• fraktury kostí chirurgie   MeSH
• hlezenní kloub fyziologie   MeSH
• lidé MeSH
• poranění kotníku MeSH
• Check Tag
• lidé MeSH

STUDY QUESTION: Do the perinatal outcomes of patients following hysteroscopic treatment for Asherman syndrome (AS) differ from that of a control population? SUMMARY ANSWER: Perinatal complications including placental issues, high blood loss, and prematurity in women after treatment for AS should be considered as moderate to high risk, especially in patients who have undergone more than one hysteroscopy (HS) or repeated postpartum instrumental revisions of the uterine cavity (Dilation and Curettage; D&C). WHAT IS KNOWN ALREADY: The detrimental impact of AS on obstetrics outcomes is commonly recognized. However, prospective studies evaluating perinatal/neonatal outcomes in women with AS history are sparse, and the characteristics accounting for the respective morbidity of AS patients remain to be elucidated. STUDY DESIGN, SIZE, DURATION: We conducted a prospective cohort study utilizing data from patients who underwent HS treatment for moderate to severe AS in a single tertiary University-affiliated hospital (enrolled between 01 January 2009 and March 2021), and who consequently conceived and progressed to at least 22nd gestational week of pregnancy. Perinatal outcomes were compared to a control population without an AS history, retrospectively enrolled concomitantly at the time of delivery for each patient with AS. Maternal and neonatal morbidity was assessed as well as the characteristics-related risk factors of AS patients. PARTICIPANTS/MATERIALS, SETTING, METHODS: Our analytic cohort included a total of 198 patients, 66 prospectively enrolled patients with moderate to severe AS and 132 controls. We used multivariable logistic regression to calculate a propensity score to match 1-1 women with and without AS history based on demographic and clinical factors. After matching, 60 pairs of patients were analysed. Chi-square test was used to compare perinatal outcomes between the pairs. Spearman's correlation analysis was utilized to investigate the correlation between perinatal/neonatal morbidity and the characteristics-related factors of AS patients. The odds ratio (OR) for the associations was calculated by logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 60 propensity matched pairs, the AS group more frequently experienced overall perinatal morbidity, including abnormally invasive placenta (41.7% vs 0%; P < 0.001), retained placenta requiring manual or surgical removal (46.7% vs 6.7%; P < 0.001), and peripartum haemorrhage occurrence (31.7% vs 3.3%; P < 0.001). Premature delivery (<37 gestational weeks) was reported more frequently also for patients with AS (28.3% vs 5.0%; P < 0.001). However, no increased frequency of intra-uterine growth restriction or worsened neonatal outcomes were observed in AS group. Univariable analysis of risk factors for AS group morbidity outcomes revealed that the main factor related to abnormally invasive placenta was two or more HS procedures (OR 11.0; 95% CI: 1.33-91.23), followed by two or more D&Cs preceding AS treatment (OR 5.11; 95% CI: 1.69-15.45), and D&C performed postpartum as compared to post abortion (OR 3.0; 95% CI: 1.03-8.71). Similarly, two or more HS procedures were observed as the most important factor for retained placenta (OR 13.75; 95% CI: 1.66-114.14), followed by two or more preceding D&Cs (OR 5.16; 95% CI: 1.67-15.9). Premature birth was significantly associated with the number of preceding D&Cs (OR for two or more, 4.29; 95% CI: 1.12-14.91). LIMITATIONS, REASONS FOR CAUTION: Although the cohort of patients with AS was enrolled prospectively, a baseline imbalance was intrinsically involved in the retrospective enrolment of the control group. However, to reduce the risk of bias, confounding factors were adjusted for using propensity score matching. The limitation to the generalization of our reported results is the single institution design in which all patients were treated for AS in one tertiary medical centre. WIDER IMPLICATIONS OF THE FINDINGS: Within our search scope, our study represents one of the first and largest prospective studies of perinatal and neonatal outcomes in moderate to severe AS patients with a prospectively analysis of the risks factors of characteristics significantly influencing reported morbidities among patients with AS. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by the Charles University in Prague [UNCE 204065] and by the institutional grant of The General Faculty Hospital in Prague [00064165]. No competing interests were declared. TRIAL REGISTRATION NUMBER: N/A.

• MeSH
• gynatrézie * MeSH
• kohortové studie MeSH
• lidé MeSH
• novorozenec MeSH
• placenta MeSH
• předčasný porod * epidemiologie   etiologie   MeSH
• prospektivní studie MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• tendenční skóre MeSH
• zadržená placenta * MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH