Metabolomic biomarker discovery for detection of early stage women’s cancers

Izhodišče Rak je ena izmed najtežjih boleznih z visoko smrtnostjo v svetovnem merilu. Kljub številnim znanstvenim odkritjem v zadnjih desetletjih, še vedno obstaja veliko neznank, kar otežuje uspešno zdravljenje. Ključnega pomena ostaja zgodnje odkrivanje bolezni, kar največ prispeva k ugodni prognozi. Namen raziskave je bil s pomočjo orodij metabolomike odkriti potencialne tumorske označevalce, ki bi bili uporabni pri zgodnjem odkrivanju raka jajčnikov, dojk ter endometrija. Preiskovanke in metode dela Delo je prospektivna raziskava, v katero je bilo vključenih 15 bolnic z rakom jajčnikov, 39 bolnic z rakom dojk, 15 bolnic z rakom endometrija, 21 zdravih žensk ter 21 bolnic z benignimi ginekološkimi obolenji, ki so bile zdravljene na Kliniki za ginekologijo in perinatologijo Univerzitetnega kliničnega centra Maribor. Vsem udeleženkam smo po opravljeni diagnostiki ter določenem stadiju bolezni odvzeli vzorce krvi za kvantitativno določitev 232 metabolitov s pomočjo HPLC-TQ/MS. Z multivariatno in univariatno analizo ter metodami strojnega učenja smo nato ob primerjavi bolnic z rakavimi obolenji in zdravih posameznic identificirali metabolite, ki najbolje ločujejo obe skupini. Izbranim označevalcem smo določili še uspešnost klasifikacije z določanjem površine pod krivuljo ter ustrezne občutljivosti in specifičnosti. Rezultati Pri raku jajčnikov smo identificirali 5 označevalcev iz skupine ceramidov in sfingomielinov (C16-ceramid, C22-ceramid, C24-ceramid, C18-sfingomielin, C18:1-sfingomielin), s pomočjo katerih smo uspeli ločiti skupino bolnic z rakom jajčnikov od zdravih žensk in tistih z benignimi ginekološkimi obolenji z občutljivostjo 83 %, specifičnostjo 80 % in AUC 0,920. Pri raku dojk so se za najpomembnejše izkazali 4 označevalci in sicer tetradecenoilkarnitin, tetradekanoilkarnitin, dodekanoilkarnitin in 9,12-linoleinska kislina, ki so dosegli 81 % občutljivost ob 81 % specifičnosti in AUC 0,839. Pri raku endometrija so bili 4 najpomembnejši označevalci C16-ceramid, C22-ceramid, hidroksiheksadecenoilkarnitin in 1-metiladenozin, ki so se izkazali z 93 % občutljivostjo ob 75 % specifičnosti in AUC 0,925. Zaključek V raziskavi smo odkrili 5 pomembnih metabolnih označevalcev, s katerimi je mogoče ločiti obolele ženske od zdravih in tistih z benignimi obolenji s podobno diagnostično natančnostjo, kot jo ponuja kombinacija trenutno uporabljanih tumorskih označevalcev CA 125 in HE4. Pri raku dojk in endometrija smo odkrili pri vsakem po 4 pomembne biološke označevalce, ki po diagnostični učinkovitosti bistveno presežejo vse do sedaj uporabljene tumorske označevalce, kar pomeni velik potencial za uporabo metabolomike v diagnostiki ginekoloških rakov v prihodnosti.Background Cancer is one of the most severe diseases with high morbidity and mortality. Despite numerous scientific breakthroughs in last decades, many questions still remain unanswered which hinder successful treatment. Early diagnosis remains a key factor to a favorable prognosis. The aim of the research was an identification of potential tumor markers with the use of metabolomics that could aid in early diagnosis of ovarian, breast and endometrial cancer. Patients and methods The research of prospective type included 15 patients with ovarian cancer, 39 patients with breast cancer, 15 patients with endometrial cancer, 21 healthy women and 21 patienst with benign gynecological diseases. All patients were recruited at the Department of gynecology and perinatology at University Medical Centre Maribor, where they received treatment. All patients were diagnosed and staged prior to recruitment. Serum blood samples were collected to quantitatively determine concentrations of 232 known metabolites using HPLC-TQ/MS. Using multivariate and univariate analysis and machine learning algorithms, best classifiers were selected. Best performing metabolited were further analysed using ROC analysis to determine their diagnostic potential. Results 5 potential tumor markers were identified for ovarian cancer that belong to the group of ceramides and sphyngomyelins (C16-ceramide, C22-ceramide, C24-ceramide, C18-sphyngomyelin, C18:1-sphyngomyelin) and demonstrated 83% sensitivity, 80% specificity and AUC 0.920 for discriminating ovarian cancer patients from healthy control group and patients with benign gynecological diseases. For breast cancer, 4 best-performing markers were tetradecenoylcarnitine, tetradecanoylcarnitine, dodecanoylcarnitine and 9,12-linoleic acid that demonstrated 81% sensitivity, 81% specificity and AUC 0.839. For endometrial cancer, 4 best-performing markers were C16-ceramide, C22-ceramide, hidroxyhexadecenoylcarnitine and 1-methyladenosine, that demonstrated 93% sensitivity, 75% specificity and AUC 0.925. Conclusion The research identified 5 potential tumor markers for ovarian cancer that enable similar or better diagnostic potential than currently used CA 125 and HE4. For breast and endometrial cancer, 4 markers were proposed respectively, that outperform all currently used tumor markers. Those findings propose great potential for metabolomics in discovery of early gynecological cancers

HOW PORT SERVICE SYSTEM DEPENDS ON SIZE OF THE VESSEL ON DEPARTURE / ARRIVAL

Zaradi hitro rastoče svetovne trgovine veliko pristanišč zagotavlja vrsto pretovora različnega tovora, kar lahko vidimo že na primeru koprskega pristanišča, kjer se ukvarjajo tako s tekočimi tovori, razsutimi tovori kot tudi z generalnim tovorom. Prav zaradi te možnosti je koprsko pristanišče postala eno izmed vodilnih pristanišč severnega Jadrana in s svojimi zmožnostmi tudi eno izmed vodilnih pristanišč za nadaljnje oskrbovanje srednje Evrope. Prav zaradi tega so številni ladjarji videli priložnost in to s pridom izkoriščali ter za svoj pretovor začeli uporabljati različne velikosti ladje, ki obiskujejo Luko Koper in na ta način prinašajo dobiček tako sebi kot tudi vsem vpletenim v proces prihoda in odhoda ladje v pristanišče. Obstaja veliko pristaniških služb, ki so zadolžene za nemoteno delovanje pristanišča in so ločene tako od del, ki se dogajajo na vodi, kot tudi od čiščenja pristanišča, zato sem se pri tem želel osredotočiti predvsem na vidik služb, ki so zadolžene za prihod in odhod ladje od najave do priveza. Skozi nalogo spoznamo, kaj so pristaniške službe in kasneje predvsem službe, ki so zadolžene za ladjo. To so piloti, vlačilci, privezovalci in kapitanija, diplomska naloga pa daje poudarek prav njim. Prav tako se mi je zdelo smiselno predstaviti, na čem temelji odločitev ladjarja, da pripelje določen tip velikosti ladje v pristanišče, saj so odločitve premišljene in vnaprej znane, saj se na današnjem trgu strmi predvsem k dobičku in ne izgubi. Predstavljeni so tudi proces prihoda in odhoda ladje, organizacija pristaniških služb, ki pri tem sodelujejo in zagotavljajo varnost tako za druga plovila kot tudi za pristanišče. Vmes so poudarjeni različni dejavniki, ki vplivajo na organizacijo služb, in kako se s korektnim upoštevanjem pravilnikov zagotavljata red in disciplina delovanja. Kot pomoč pri raziskavi sem se odločil raziskati tudi primere pomorskih incidentov, ki so se zgodili v okolici ali sami Luki Koper, in sicer zaradi lažjega razumevanja delovanja pristaniških služb ob incidentih.Due to the fast-growing world trade, many ports ensure transhipment of different cargoes, a good example of which is the Port of Koper, where liquid cargo, bulk cargo and general cargo are loaded and unloaded. It is thanks to this possibility that the Port of Koper has become one of the leading ports in the North Adriaticmoreover, owing to its capabilities, it has also become one of the leading ports in supplying Central Europe. For this reason, many shipowners seized this opportunity by visiting the Port of Koper with different sizes of ships for their transhipment. In doing so, they generate profit for themselves and for everyone involved in the ships’ arrival to the port or their departure from it. Many port authorities are responsible for undisturbed functioning of the porttheir work ranges from performing tasks at the sea to cleaning the port. This is why I decided to focus on the authorities who are in charge of monitoring the ships’ arrival and departure, including all procedures from arrival notification to mooring the ship. The paper presents port authorities, with a particular emphasis on the authorities responsible for the ship itself, namely pilots, tuggers, employees mooring the ships and harbourmasters. Furthermore, it seemed reasonable to present how a shipowner decides on the size of the ship to be brought to the portthese decisions are well-considered and known in advance as the modern market strives for profit rather than loss. I also present the ships’ arrival and departure as well as the organisation of port authorities that are involved in the process and, at the same time, ensure the security for other vessels and the port itself. Different factors affecting the organisation of the authorities are stressedmoreover, I describe how order and discipline are ensured by following the regulations. To better understand the functioning of the port authorities in case of incidents, I examined cases of maritime incidents that occurred in the Port of Koper or its surroundings

The reliability of preoperative determination of tumour grade in endometrial cancer

Endometrial carcinoma is the most common among gynaecological cancers. The most frequent symptom of this disease is postmenopausal bleeding. The diagnosis of endometrial cancer has to be histologically confirmed and there are several methods for endometrial sampling with which we obtain the cells or the endometrial tissue. The reliability of these methods differs. With histologically confirmed diagnosis we determine histological subtype and tumour grade. Those are the two key features that have the most important impact on the probability of disease spread and recurrence, but the most important fact is that they help us to determine the optimal extent of surgical treatment. The reliability of the preoperative determination of tumour grade weakly correlates with the final histological diagnosis, especially with preoperatively diagnosed G1-G2 endometrioid adenocarcinomas, while with G3 carcinomas, which are high-risk histologies, the concordance of the preoperative and postoperative interpretation of the histological findings is much higher

Data on metabolomic profiling of ovarian cancer patients' serum for potential diagnostic biomarkers

The data presented here are related to the research paper entitled “Metabolomic profiling suggests long chain ceramides and sphingomyelins as a possible diagnostic biomarker of epithelial ovarian cancer.” (Kozar et al., 2018) [1]. Metabolomic profiling was performed on 15 patients with ovarian cancer, 21 healthy controls and 21 patients with benign gynecological conditions. HPLC-TQ/MS was performed on all samples. PLS-DA was used for the first line classification of epithelial ovarian cancer and healthy control group based on metabolomic profiles. Random forest algorithm was used for building a prediction model based over most significant markers. Univariate analysis was performed on individual markers to determine their distinctive roles. Furthermore, markers were also evaluated for their biological significance in cancer progression