Browsing by Author "Eglītis, Jānis"

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    CD63 and Dna Mismatch Repair Protein Expression in Prostate Cancer
    (2021-06-01) Folkmanis, Kristofs; Eglītis, Jānis; Jakubovskis, Māris; Lietuvietis, Vilnis; Folkmane, Inese; Isajevs, Sergejs; Rīga Stradiņš University
    Protein expression levels in immunohistochemistry and molecular biomarkers have been reported for their ability to predict recurrence, progression, development of metastases, and patient survival. The molecular features in low- and high-grade prostate cancer can differ and influence treatment decision and prognosis. The objective of the current study was to compare the expression of exosomal biomarkers CD63 and mismatch repair proteins (MSH2, MSH6, MLH1, and PMS2) by immunohistochemistry (IHC) in tissue of patients with prostate cancer and benign hyperplasia. Altogether, 62 patients with prostate acinar adenocarcinoma and 20 patients with prostate benign hyperplasia were enrolled in this retrospective study. CD63, MSH2, MSH6, MLH1, and PMS2 expression was analysed by immunohistochemistry. The obtained results showed that CD63 expression was significantly higher in patients with Grade III-V prostate cancer compared to Grade I-II, respectively; 2.23 (1-3) vs 0.92 (0-2) score, p = 0.001. In addition, a significant positive correlation between CD63 expression and grade groups was revealed (Rho = +0.54; p < 0.0001). Furthermore, progression-free survival was significantly higher in patients with low CD63 expression, compared to high CD63 expression (p = 0.0007). MMR expression was absent in 14 patients (four patients with Grade I-II cancer and 10 patients with Grade III-cancer). MMR was present in all cases of benign prostate hyperplasia (mild to moderate staining). The conclusion was that high grade prostate cancer (Grade groups III-V) was characterised by increased CD63 expression, which correlated with progression-free survival.
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    Comprehensive characterization of RNA cargo of extracellular vesicles in breast cancer patients undergoing neoadjuvant chemotherapy
    (2022-10-26) Sadovska, Lilite; Zayakin, Pawel; Eglītis, Kristaps; Endzeliņš, Edgars; Radoviča-Spalviņa, Ilze; Avotiņa, Elīza; Auders, Jānis; Keiša, Laura; Liepniece-Karele, Inta; Leja, Mārcis; Eglītis, Jānis; Linē, Aija; Department of Pathology
    Extracellular vesicles (EVs) are g7aining increased attention as carriers of cancer-derived molecules for liquid biopsies. Here, we studied the dynamics of EV levels in the plasma of breast cancer (BC) patients undergoing neoadjuvant chemotherapy (NAC) and explored the relevance of their RNA cargo for the prediction of patients’ response to the therapy. EVs were isolated from serial blood samples collected at the time of diagnosis, at the end of NAC, and 7 days, 6, and 12 months after the surgery from 32 patients with locally advanced BC, and 30 cancer-free healthy controls (HCs) and quantified by nanoparticle tracking analysis. The pre-treatment levels of EVs in BC patients were higher than in HCs, significantly increased during the NAC and surgery, and decreased to the levels found in HCs 6 months after surgery, thus showing that a substantial fraction of plasma EVs in BC patients are produced due to the disease processes and treatment. RNA sequencing analysis revealed that the changes in the EV levels were associated with the alterations in the proportions of various RNA biotypes in EVs. To search for RNA biomarkers that predict response to the NAC, patients were dichotomized as responders and non-responders based on Miller-Payne grades and differential expression analyses were carried out between responders and non-responders, and HCs. This resulted in the identification of 6 miRNAs, 4 lncRNAs, and 1 snoRNA that had significantly higher levels in EVs from non-responders than responders at the time of diagnosis and throughout the NAC, and significantly lower levels in HCs, thus representing biomarkers for the prediction of response to NAC at the time of diagnosis. In addition, we found 14 RNAs representing piRNA, miRNA, lncRNA, snoRNA, and snRNA biotypes that were induced by NAC in non-responders and 2 snoRNAs and 1 piRNA that were induced by NAC in patients with early disease progression, thus warranting further functional studies on their role in chemoresistance and metastasis.
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    Extracellular Vesicles—A Source of RNA Biomarkers for the Detection of Breast Cancer in Liquid Biopsies
    (2023-09) Zayakin, Pawel; Sadovska, Lilite; Eglītis, Kristaps; Romanchikova, Nadezhda; Radoviča-Spalviņa, Ilze; Endzeliņš, Edgars; Liepniece-Karele, Inta; Eglītis, Jānis; Linē, Aija; Department of Pathology
    Over the past decade, extracellular vesicles (EVs) have emerged as a promising source of cancer-derived RNAs for liquid biopsies. However, blood contains a pool of heterogeneous EVs released by a variety of cell types, making the identification of cancer RNA biomarkers challenging. Here, we performed deep sequencing of plasma EV RNA cargo in 32 patients with locally advanced breast cancer (BC) at diagnosis and 7 days after breast surgery and in 30 cancer-free healthy controls (HCs). To identify BC-derived RNA biomarkers, we searched for RNAs that had higher levels in BC EVs at the time of diagnosis compared with HCs and decreased after surgery. Data analysis showed that the fractions of miRNAs, snRNAs, snoRNAs, and tRFs were increased, but the fraction of lncRNAs was decreased in BC EVs as compared to HCs. BC-derived biomarker candidates were identified across various RNA biotypes. Considered individually, they had very high specificity but moderate sensitivity for the detection of BC, whereas a biomarker model composed of eight RNAs: SNORD3H, SNORD1C, SNORA74D, miR-224-5p, piR-32949, lnc-IFT-122-2, lnc-C9orf50-4, and lnc-FAM122C-3 was able to distinguish BC from HC EVs with an AUC of 0.902 (95% CI = 0.872–0.931, p = 3.4 × 10−9) in leave-one-out cross-validation. Furthermore, a number of RNA biomarkers were correlated with the ER and HER2 expression and additional biomarker models were created to predict hormone receptor and HER2 status. Overall, this study demonstrated that the RNA composition of plasma EVs is altered in BC patients and that they contain cancer-derived RNA biomarkers that can be used for BC detection and monitoring using liquid biopsies.
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    Heavy Resistance Training in Breast Cancer Patients Undergoing Adjuvant Therapy
    (2020-06-01) Cešeiko, Rūdolfs; Thomsen, Simon Nørskov; Tomsone, Signe; Eglītis, Jānis; Vētra, Aivars; Srebnijs, Andrejs; Timofejevs, Mihails; Purmalis, Egīls; Wang, Eivind; Department of Rehabilitation
    BACKGROUND AND PURPOSE: Adjuvant breast cancer therapy may reduce maximal muscle strength, muscle mass, and functional performance. Although maximal strength training (MST) has the potential to counteract this debilitating outcome and is shown to be superior to low- and moderate-intensity strength training, it is unknown if it can elicit effective adaptations in patients suffering treatment-induced adverse side effects. METHODS: Fifty-five newly diagnosed stage I to III breast cancer patients (49 ± 7 yr) scheduled for adjuvant therapy were randomized to MST or a control group. The MST group performed 4 × 4 repetitions of dynamic leg press at approximately 90% of one-repetition maximum (1RM) twice a week for 12 wk. RESULTS: In the MST group, improvements in 1RM (20% ± 8%; P < 0.001) were accompanied by improved walking economy (9% ± 8%) and increased time to exhaustion during incremental walking (9% ± 8%; both P < 0.01). Moreover, the MST group increased 6-min walking distance (6MWD; 10% ± 7%), and chair rising (30% ± 20%) and stair climbing performance (12% ± 7%; all P < 0.001). All MST-induced improvements were different from the control group (P < 0.01) which reduced their 1RM (9% ± 5%), walking economy (4% ± 4%), time to exhaustion (10% ± 8%), 6MWD (5% ± 5%), chair rising performance (12% ± 12%), and stair climbing performance (6% ± 8%; all P < 0.01). Finally, although MST maintained estimated quadriceps femoris muscle mass, a decrease was observed in the control group (7% ± 10%; P < 0.001). The change in 1RM correlated with the change in walking economy (r = 0.754), time to exhaustion (r = 0.793), 6MWD (r = 0.807), chair rising performance (r = 0.808), and stair climbing performance (r = 0.754; all P < 0.001). CONCLUSIONS: Lower-extremity MST effectively increases lower-extremity maximal muscle strength in breast cancer patients undergoing adjuvant therapy and results in improved work economy, functional performance, and maintenance of muscle mass. These results advocate that MST should be considered in breast cancer treatment.