1. Initiation and elongation factor co-expression correlates with recurrence and survival in epithelial ovarian cancerMonika Sobočan, Daniela Brunialti, S Sprung, Christoph Schatz, Jure Knez, Rajko Kavalar, Iztok Takač, Johannes Haybaeck, 2022, izvirni znanstveni članek Opis: High grade epithelial ovarian cancer (EOC) represents a diagnostic and therapeutic challenge due to its aggressive features and short recurrence free survival (RFS) after primary treatment. Novel targets to inform our understanding of the EOC carcinogenesis in the translational machinery can provide us with independent prognostic markers and provide drugable targets. We have identified candidate eukaryotic initiation factors (eIF) and eukaryotic elongation factors (eEF) in the translational machinery for differential expression in EOC through in-silico analysis. We present the analysis of 150 ovarian tissue microarray (TMA) samples on the expression of the translational markers eIF2α, eIF2G, eIF5 (eIF5A and eIF5B), eIF6 and eEF1A1. All translational markers were differentially expressed among non-neoplastic ovarian samples and tumour samples (borderline tumours and EOC). In EOC, expression of eIF5A was found to be significantly correlated with recurrence free survival (RFS) and expression of eIF2G and eEF1A1 with overall survival (OS). Expression correlation among factor subunits showed that the correlation of eEF1A1, eIF2G, EIF2α and eIF5A were significantly interconnected. eIF5A was also correlated with eIF5B and eIF6. Our study demonstrates that EOCs have different translational profile compared to benign ovarian tissue and that eIF5A is a central dysregulated factor of the translation machinery.
Ključne besede: epithelial ovarian cancer, initiation and elongation factor, translational markers
Objavljeno v DKUM: 12.12.2024; Ogledov: 0; Prenosov: 2
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2. Changes in the extracellular matrix in endometrial and cervical cancer : a systematic reviewTjaša Padežnik, Anja Oleksy, Andrej Cokan, Iztok Takač, Monika Sobočan, 2023, pregledni znanstveni članek Opis: Endometrial and cervical cancers are the two most common gynaecological malignancies and among the leading causes of death worldwide. The extracellular matrix (ECM) is an important component of the cellular microenvironment and plays an important role in developing and regulating normal tissues and homeostasis. The pathological dynamics of the ECM contribute to several different processes such as endometriosis, infertility, cancer, and metastasis. Identifying changes in components of ECM is crucial for understanding the mechanisms of cancer development and its progression. We performed a systematic analysis of publications on the topic of changes in the extracellular matrix in cervical and endometrial cancer. The findings of this systematic review show that matrix metalloproteinases (MMP) play an important role impacting tumour growth in both types of cancer. MMPs degrade various specific substrates (collagen, elastin, fibronectin, aggrecan, fibulin, laminin, tenascin, vitronectin, versican, nidogen) and play a crucial role in the basal membrane degradation and ECM components. Similar types of MMPs were found to be increased in both cancers, namely, MMP-1, MMP-2, MMP-9, and MMP-11. Elevated concentrations of MMP-2 and MMP-9 were correlated with the FIGO stage and are associated with poor prognosis in endometrial cancer, whereas in cervical cancer, elevated concentrations of MMP-9 have been associated with a better outcome. Elevated ADAMTS levels were found in cervical cancer tissues. Elevated disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) levels were also found in endometrial cancer, but their role is still unclear. Following these findings, this review reports on tissue inhibitors of ECM enzymes, MMPs, and ADAMTS. The present review demonstrates changes in the extracellular matrix in cervical and endometrial cancers and compared their effect on cancer development, progression, and patient prognosis.
Ključne besede: extracellular matrix, endometrial cancer, cervical cancer
Objavljeno v DKUM: 02.12.2024; Ogledov: 0; Prenosov: 0
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3. Isoform-level transcriptome analysis of peripheral blood mononuclear cells from breast cancer patients identifies a disease-associated RASGEF1A isoformHelena Sabina Čelešnik, Mario Gorenjak, Martina Krušič, Bojana Crnobrnja, Monika Sobočan, Iztok Takač, Darja Arko, Uroš Potočnik, 2024, izvirni znanstveni članek Opis: Breast cancer (BC) comprises multiple subtypes with distinct molecular features, which differ in their interplay with host immunity, prognosis, and treatment. Non-invasive blood analyses can provide valuable insights into systemic immunity during cancer. The aim of this study was to analyze the expression of transcriptional isoforms in peripheral blood mononuclear cells (PBMCs) from BC patients and healthy women to identify potential BC immune biomarkers. Methods: RNA sequencing and isoform-level bioinformatics were performed on PBMCs from 12 triple-negative and 13 luminal A patients. Isoform expression validation by qRT-PCR and clinicopathological correlations were performed in a larger cohort (156 BC patients and 32 healthy women). Results: Transcriptional analyses showed a significant (p < 0.001) decrease in the ENST00000374459 RASGEF1A isoform in PBMCs of BC compared to healthy subjects, indicating disease-related expression changes. The decrease was associated with higher ctDNA and Ki-67 values. Conclusions: The levels of the RASGEF1A transcriptional isoform ENST00000374459 may have the potential to distinguish between BC and healthy subjects. The downregulation of ENST00000374459 in breast cancer is associated with higher proliferation and ctDNA shedding. Specialized bioinformatics analyses such as isoform analyses hold significant promise in the detection of biomarkers, since standard RNA sequencing analyses may overlook specific transcriptional changes that may be disease-associated and biologically important.
Ključne besede: breast cancer, peripheral blood, isoform-level RNA-seq, RASGEF1A ENST00000374459, ctDNA, Ki-67
Objavljeno v DKUM: 26.11.2024; Ogledov: 0; Prenosov: 3
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5. Early detection of neck lymph node metastases in breast cancer patients : the role of ultrasound and fine needle biopsyJanez Rebol, Peter Balon, Peter Kokol, Boštjan Lanišnik, Iztok Takač, Andraž Dovnik, Nina Fokter Dovnik, Monika Sobočan, Darja Arko, 2019, izvirni znanstveni članek Ključne besede: metastases, neck lymph, ultrasound, fine needle biopsy, breast canser
Objavljeno v DKUM: 27.03.2024; Ogledov: 225; Prenosov: 6
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6. Ultra-high-risk gestational choriocarcinoma of the ovary associated with ectopic pregnancyEva Pavla Malovrh, Nuša Lukinovič, Tatjana Bujas, Monika Sobočan, Jure Knez, 2023, drugi znanstveni članki Opis: Gestational choriocarcinoma of the ovary is an exceptionally rare and highly aggressive tumor. Preoperative diagnosis of extrauterine choriocarcinoma is difficult due to nonspecific clinical presentation and its resemblance to ectopic pregnancy. Without molecular genetic analysis, it is not possible to reliably differentiate gestational from non-gestational choriocarcinoma. Here, we present a case of a 44-year-old woman who presented to our emergency department with complaints of pelvic pain, vaginal bleeding, and amenorrhea. Because of a recent history of conservatively managed ectopic pregnancy, the patient underwent emergency laparoscopy. Right-sided salpingo-oophorectomy was performed due to intraoperatively suspected ovarian ectopic pregnancy. Histopathology results revealed the diagnosis of ovarian choriocarcinoma of possible gestational origin. It was classified as FIGO stage IV and WHO ultra-high-risk, and she underwent multi-agent chemotherapy without major complications. She has remained in complete remission after a 12-month follow-up. Considering the rarity of this diagnosis, we conducted a literature review including all published cases of suspected gestational choriocarcinomas of the ovary. We conclude that due to the rarity of this entity, preoperative differentiating between ovarian ectopic pregnancy and ovarian choriocarcinoma is extremely challenging, and without molecular genetic analysis, it is not possible to identify the genetic origin of the tumor.
Ključne besede: ovarian choriocarcinoma, gestational trophoblastic neoplasia
Objavljeno v DKUM: 21.02.2024; Ogledov: 302; Prenosov: 9
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8. Translacijski nadzor biologije raka jajčnikovMonika Sobočan, 2023, doktorska disertacija Opis: Rak jajčnikov (OC) se uvršča na peto mesto med vzroki za smrt žensk po vsem svetu. Razumevanje zapletenosti različnih histoloških podtipov je ključno za usmerjeno personalizirano zdravljenje bolezni. Epitelijski rak jajčnikov (EOC) je agresiven in ima omejeno preživetje brez ponovitve (RFS) po primarnem zdravljenju. Raziskovanje novih tarč za razumevanje karcinogeneze EOC v procesu translacije lahko omogoči prepoznavo novih, neodvisnih prognostičnih označevalcev in terapevtske cilje.
Metode: Po in silico analizi evkariotskih faktorjev iniciacije in elongacije (eIF in eEF) so bili vzorci tkiva jajčnika (neoplastični, ne-neoplastični) pripravljeni s pomočjo tehnike tkivnih mikromrež (TMA). Nato so vzorci bili obarvani z imunohistokemičnemi barvami za translacijske označevalce. Intenzivnost/obseg barvanja je bil analiziran glede na parametre RFS in celokupnega preživetja po zdravljenju.
Rezultati: Opazili smo statistično pomembno razliko v izraženosti translacijskih označevalcev med ne-neoplastičnimi in tumorskimi vzorci (mejni tumorji, EOC). Zlasti je eIF5A pomembno koreliral z RFS; eIF2G in eEF1A1 sta korelirala s celotnim preživetjem (OS) pri EOC. eIF5A je kazal povezave z eIF5B in eIF6, kar nakazuje njegovo osrednjo vlogo pri disfunkciji translacijskega mehanizma pri EOC.
Zaključek: Raziskava poudarja različen translacijski profil EOC v primerjavi z benignim tkivom jajčnikov. eIF5A se kaže kot ključen pri nenormalnem translacijskem mehanizmu EOC, kar bi lahko služilo kot prognostični označevalec in terapevtski cilj.
Ključne besede: rak jajčnikov, evkariotski iniciacijski faktorji, evkariontski elongacijski faktorji
Objavljeno v DKUM: 02.10.2023; Ogledov: 433; Prenosov: 53
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