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  1. Article ; Online: Expression profiles of small non-coding RNAs in breast cancer tumors characterize clinicopathological features and show prognostic and predictive potential.

    Kärkkäinen, Emmi / Heikkinen, Sami / Tengström, Maria / Kosma, Veli-Matti / Mannermaa, Arto / Hartikainen, Jaana M

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 22614

    Abstract: Precision medicine approaches are required for more effective therapies for cancer. As small non-coding RNAs (sncRNAs) have recently been suggested as intriguing candidates for cancer biomarkers and have shown potential also as novel therapeutic targets, ...

    Abstract Precision medicine approaches are required for more effective therapies for cancer. As small non-coding RNAs (sncRNAs) have recently been suggested as intriguing candidates for cancer biomarkers and have shown potential also as novel therapeutic targets, we aimed at profiling the non-miRNA sncRNAs in a large sample set to evaluate their role in invasive breast cancer (BC). We used small RNA sequencing and 195 fresh-frozen invasive BC and 22 benign breast tissue samples to identify significant associations of small nucleolar RNAs, small nuclear RNAs, and miscellaneous RNAs with the clinicopathological features and patient outcome of BC. Ninety-six and five sncRNAs significantly distinguished (Padj < 0.01) invasive local BC from benign breast tissue and metastasized BC from invasive local BC, respectively. Furthermore, 69 sncRNAs significantly associated (Padj < 0.01) with the tumor grade, hormone receptor status, subtype, and/or tumor histology. Additionally, 42 sncRNAs were observed as candidates for prognostic markers and 29 for predictive markers for radiotherapy and/or tamoxifen response (P < 0.05). We discovered the clinical relevance of sncRNAs from each studied RNA type. By introducing new sncRNA biomarker candidates for invasive BC and validating the potential of previously described ones, we have guided the way for further research that is warranted for providing novel insights into BC biology.
    MeSH term(s) Humans ; Animals ; Female ; RNA, Small Untranslated/genetics ; RNA, Small Untranslated/metabolism ; Breast Neoplasms/genetics ; Prognosis ; Sequence Analysis, RNA ; Mammary Neoplasms, Animal
    Chemical Substances RNA, Small Untranslated
    Language English
    Publishing date 2022-12-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-26954-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The debatable presence of PIWI-interacting RNAs in invasive breast cancer.

    Kärkkäinen, Emmi / Heikkinen, Sami / Tengström, Maria / Kosma, Veli-Matti / Mannermaa, Arto / Hartikainen, Jaana M

    Cancer medicine

    2021  Volume 10, Issue 11, Page(s) 3593–3603

    Abstract: Numerous factors influence breast cancer (BC) prognosis, thus complicating the prediction of outcome. By identifying biomarkers that would distinguish the cases with poorer response to therapy already at the time of diagnosis, the rate of survival could ... ...

    Abstract Numerous factors influence breast cancer (BC) prognosis, thus complicating the prediction of outcome. By identifying biomarkers that would distinguish the cases with poorer response to therapy already at the time of diagnosis, the rate of survival could be improved. Lately, Piwi-interacting RNAs (piRNAs) have been introduced as potential cancer biomarkers, however, due to the recently raised challenges in piRNA annotations, further evaluation of piRNAs' involvement in cancer is required. We performed small RNA sequencing in 227 fresh-frozen breast tissue samples from the Eastern Finnish Kuopio Breast Cancer Project material to study the presence of piRNAs in BC and their associations with the clinicopathological features and outcome of BC patients. We observed the presence of three small RNAs annotated as piRNA database entries (DQ596932, DQ570994, and DQ571955) in our samples. The actual species of these RNAs however remain uncertain. All three small RNAs were upregulated in grade III tumors and DQ596932 additionally in estrogen receptor negative tumors. Furthermore, patients with estrogen receptor positive BC and higher DQ571955 had shorter relapse-free survival and poorer BC-specific survival, thus indicating DQ571955 as a candidate predictive marker for radiotherapy response in estrogen receptor positive BC. DQ596932 showed possible prognostic value in BC, whereas DQ570994 was identified as a candidate predictive marker for tamoxifen and chemotherapy response. These three small RNAs appear as candidate biomarkers for BC, which could after further investigation provide novel approaches for the treatment of therapy resistant BC. Overall, our results indicate that the prevalence of piRNAs in cancer is most likely not as comprehensive as has been previously thought.
    MeSH term(s) Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/analysis ; Breast/chemistry ; Breast Neoplasms/chemistry ; Breast Neoplasms/mortality ; Breast Neoplasms/pathology ; Breast Neoplasms/therapy ; Disease-Free Survival ; Female ; Humans ; Neoplasm Grading ; Prognosis ; RNA, Small Interfering/analysis ; Radiotherapy ; Receptors, Estrogen/analysis ; Sequence Analysis, RNA ; Tamoxifen/therapeutic use ; Treatment Outcome ; Up-Regulation
    Chemical Substances Antineoplastic Agents ; Biomarkers, Tumor ; RNA, Small Interfering ; Receptors, Estrogen ; Tamoxifen (094ZI81Y45)
    Language English
    Publishing date 2021-05-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2659751-2
    ISSN 2045-7634 ; 2045-7634
    ISSN (online) 2045-7634
    ISSN 2045-7634
    DOI 10.1002/cam4.3915
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Tumor-independent Detection of Inherited Mismatch Repair Deficiency for the Diagnosis of Lynch Syndrome with High Specificity and Sensitivity.

    Kansikas, Minttu / Vähätalo, Laura / Kantelinen, Jukka / Kasela, Mariann / Putula, Jaana / Døhlen, Anni / Paloviita, Pauliina / Kärkkäinen, Emmi / Lahti, Niklas / Arnez, Philippe / Kilpinen, Sami / Alcala-Repo, Beatriz / Pylvänäinen, Kirsi / Pöyhönen, Minna / Peltomäki, Päivi / Järvinen, Heikki J / Seppälä, Toni T / Renkonen-Sinisalo, Laura / Lepistö, Anna /
    Mecklin, Jukka-Pekka / Nyström, Minna

    Cancer research communications

    2023  Volume 3, Issue 3, Page(s) 361–370

    Abstract: Lynch syndrome (LS) is the most common hereditary cancer syndrome. Early diagnosis improves prognosis and reduces health care costs, through existing cancer surveillance methods. The problem is finding and diagnosing the cancer predisposing genetic ... ...

    Abstract Lynch syndrome (LS) is the most common hereditary cancer syndrome. Early diagnosis improves prognosis and reduces health care costs, through existing cancer surveillance methods. The problem is finding and diagnosing the cancer predisposing genetic condition. The current workup involves a complex array of tests that combines family cancer history and clinical phenotypes with tumor characteristics and sequencing data, followed by a challenging task to interpret the found variant(s). On the basis of the knowledge that an inherited mismatch repair (MMR) deficiency is a hallmark of LS, we have developed and validated a functional MMR test, DiagMMR, that detects inherited MMR deficiency directly from healthy tissue without need of tumor and variant information. The validation included 119 skin biopsies collected from clinically pathogenic MMR variant carriers (
    Significance: Clinical validation of DiagMMR shows high accuracy in distinguishing individuals with hereditary MSH2 or MSH6 MMR deficiency (i.e., LS). The method presented overcomes challenges faced by the complexity of current methods and can be used alone or with conventional tests to improve the ability to recognize genetically predisposed individuals.
    MeSH term(s) Humans ; Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis ; MutS Homolog 2 Protein/genetics ; Pilot Projects ; Colorectal Neoplasms/genetics ; Genetic Predisposition to Disease
    Chemical Substances MutS Homolog 2 Protein (EC 3.6.1.3)
    Language English
    Publishing date 2023-03-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2767-9764
    ISSN (online) 2767-9764
    DOI 10.1158/2767-9764.CRC-22-0384
    Database MEDical Literature Analysis and Retrieval System OnLINE

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