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Tjon-Kon-Fat, Lee-Ann
Alternative names
Publications (9 of 9) Show all publications
In ’t Veld, S. G. .., Arkani, M., Post, E., Antunes-Ferreira, M., D'Ambrosi, S., Vessies, D. C. .., . . . Wurdinger, T. (2022). Detection and localization of early- and late-stage cancers using platelet RNA. Cancer Cell, 40(9), 999-1009.e6
Open this publication in new window or tab >>Detection and localization of early- and late-stage cancers using platelet RNA
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2022 (English)In: Cancer Cell, ISSN 1535-6108, E-ISSN 1878-3686, Vol. 40, no 9, p. 999-1009.e6Article in journal (Refereed) Published
Abstract [en]

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.

Place, publisher, year, edition, pages
Elsevier, 2022
Keywords
blood, blood platelets, cancer, early detection, liquid biopsy, RNA, TEP
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-199458 (URN)10.1016/j.ccell.2022.08.006 (DOI)000888756000014 ()36055228 (PubMedID)2-s2.0-85137385164 (Scopus ID)
Funder
EU, Horizon 2020
Available from: 2022-09-27 Created: 2022-09-27 Last updated: 2023-09-05Bibliographically approved
Åberg, A.-M., Halin Bergström, S., Thysell, E., Tjon-Kon-Fat, L.-A., Nilsson, J. A., Widmark, A., . . . Lundholm, M. (2021). High monocyte count and expression of s100a9 and s100a12 in peripheral blood mononuclear cells are associated with poor outcome in patients with metastatic prostate cancer. Cancers, 13(10), Article ID 2424.
Open this publication in new window or tab >>High monocyte count and expression of s100a9 and s100a12 in peripheral blood mononuclear cells are associated with poor outcome in patients with metastatic prostate cancer
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2021 (English)In: Cancers, ISSN 2072-6694, Vol. 13, no 10, article id 2424Article in journal (Refereed) Published
Abstract [en]

Increasing evidence indicates calcium-binding S100 protein involvement in inflammation and tumor progression. In this prospective study, we evaluated the mRNA levels of two members of this family, S100A9 and S100A12, in peripheral blood mononuclear cells (PBMCs) in a cohort of 121 prostate cancer patients using RT-PCR. Furthermore, monocyte count was determined by flow cytometry. By stratifying patients into different risk groups, according to TNM stage, Gleason score and PSA concentration at diagnosis, expression of S100A9 and S100A12 was found to be significantly higher in patients with metastases compared to patients without clinically detectable metastases. In line with this, we observed that the protein levels of S100A9 and S100A12 in plasma were higher in patients with advanced disease. Importantly, in patients with metastases at diagnosis, high monocyte count and high levels of S100A9 and S100A12 were significantly associated with short progression free survival (PFS) after androgen deprivation therapy (ADT). High monocyte count and S100A9 levels were also associated with short cancer-specific survival, with monocyte count providing independent prognostic information. These findings indicate that circulating levels of monocytes, as well as S100A9 and S100A12, could be biomarkers for metastatic prostate cancer associated with particularly poor prognosis.

Place, publisher, year, edition, pages
MDPI, 2021
Keywords
Metastases, Monocytes, Peripheral blood mononuclear cells, Prostate cancer, S100A12, S100A9
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-183631 (URN)10.3390/cancers13102424 (DOI)000654662200001 ()2-s2.0-85105817619 (Scopus ID)
Available from: 2021-05-27 Created: 2021-05-27 Last updated: 2023-09-05Bibliographically approved
Tjon-Kon-Fat, L.-A., Köhn, L., Best, M., Lundholm, M., Wurdinger, T., Widmark, A., . . . Nilsson, J. (2020). Tumor-educated platelets for early prostate cancer diagnosis, and therapy stratification in patients with metastasized castration resistant prostate cancer. Paper presented at AACR Special Conference on Advances in Liquid Biopsies, JAN 13-16, 2020, Miami, FL. Clinical Cancer Research, 26(11), 73-74
Open this publication in new window or tab >>Tumor-educated platelets for early prostate cancer diagnosis, and therapy stratification in patients with metastasized castration resistant prostate cancer
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2020 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 26, no 11, p. 73-74Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
American Association for Cancer Research, 2020
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-172502 (URN)000537848000100 ()
Conference
AACR Special Conference on Advances in Liquid Biopsies, JAN 13-16, 2020, Miami, FL
Available from: 2020-07-03 Created: 2020-07-03 Last updated: 2020-07-03Bibliographically approved
Tjon-Kon-Fat, L.-A. (2018). Circulating platelets: a novel liquid biopsy source for cancer diagnostics and therapy stratification. (Doctoral dissertation). Umeå: Umeå University
Open this publication in new window or tab >>Circulating platelets: a novel liquid biopsy source for cancer diagnostics and therapy stratification
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

As conventional tissue biopsies have several drawbacks, much effort has been directed toward the development of minimal-invasive liquid biopsy platforms for detecting and profiling cancer.

Platelets are the second most abundant cells in blood and have very versatile functions both in physiological and pathophysiological conditions. When exposed to tumors and their environment, platelets exchange biomolecules with tumor cells changing the platelets’ RNA profile, resulting in tumor-mediated education of the platelets. Our research group and collaborators have previously shown that platelets sequester material while in circulation and with that ability accumulate cancer specific information. Platelet RNA profiles or detection of tumor-derived biomarkers within them may provide insight into ongoing cancer-related processes in a patient, allowing for implementation of personalized therapy strategies.

This thesis evaluates whether circulating platelets could have a potential role (as a liquid biopsy source) in cancer diagnostics, therapy stratification, and monitoring of the disease. Gene expression analysis using digital droplet PCR and RNA-sequencing were the main methods used to address this. Prostate Cancer is the main model used in this thesis but this platform is applicable to other tumor types such as colorectal-, breast-, and lung cancer.

We found platelets of cancer patients to contain tumor-derived information enabling selection of biomarker panels discriminating early stage cancer patients from healthy individuals as well as therapy responders from non-responders with high accuracy. The RNA transcript within the platelets was more informative in regards to therapy stratification compared to circulating free DNA of matched patient samples, in which genomic changes were analyzed. Combining both increased the accuracy in predicting therapy outcome.

Platelets show usefulness as a novel liquid biopsy source for early detection and individualizing patient therapy decisions (for personalized medicine). The techniques used are promising but large-scale validation is necessary.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2018. p. 46
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1952
Keywords
platelets, biomarkers, liquid biopsy, therapy stratification, personalised medicine, Prostate cancer
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-146032 (URN)978-91-7601-838-5 (ISBN)
Public defence
2018-04-20, Sal 933, 9 trp, byggnad 3A, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2018-03-28 Created: 2018-03-26 Last updated: 2018-06-09Bibliographically approved
Tjon-Kon-Fat, L.-A., Sol, N., Wurdinger, T. & Nilsson, R. J. (2018). Platelet RNA in Cancer Diagnostics. Seminars in Thrombosis and Hemostasis, 44(2), 135-141
Open this publication in new window or tab >>Platelet RNA in Cancer Diagnostics
2018 (English)In: Seminars in Thrombosis and Hemostasis, ISSN 0094-6176, E-ISSN 1098-9064, Vol. 44, no 2, p. 135-141Article in journal (Refereed) Published
Abstract [en]

Platelets are involved in several steps of cancer metastasis. During this process, platelets are exposed to the tumor and its environment, thereby exchanging biomolecules with the tumor cells and resulting in tumor-mediated education of the platelets and a change in their RNA profile. Analysis of platelet RNA profiles or direct measurement of tumor-derived biomarkers within platelets can provide information on ongoing cancer-related processes in the individual (e.g., whether the patient has cancer, the tumor type, and possibly identify oncogenic alterations driving the disease for treatment selection). The close interaction with the disease process and the ability to respond to systemic alterations make platelets an interesting biosource for implementation in precision medicine.

Place, publisher, year, edition, pages
THIEME MEDICAL PUBL INC, 2018
Keywords
platelets, biomarkers, liquid biopsy
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-145772 (URN)10.1055/s-0037-1606182 (DOI)000426118100007 ()28905353 (PubMedID)2-s2.0-85029755219 (Scopus ID)
Available from: 2018-06-18 Created: 2018-06-18 Last updated: 2018-06-18Bibliographically approved
Tjon-Kon-Fat, L.-A., Lundholm, M., Schröder, M., Wurdinger, T., Thellenberg-Karlsson, C., Widmark, A., . . . Nilsson, R. J. (2018). Platelets harbor prostate cancer biomarkers and the ability to predict therapeutic response to abiraterone in castration resistant patients. The Prostate, 78(1), 48-53
Open this publication in new window or tab >>Platelets harbor prostate cancer biomarkers and the ability to predict therapeutic response to abiraterone in castration resistant patients
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2018 (English)In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 78, no 1, p. 48-53Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Novel therapies for castration resistant prostate cancer (CRPC) have been introduced in the clinic with possibilities for individualized treatment plans. Best practice of those expensive drugs requires predictive biomarker monitoring. This study used circulating biomarker analysis to follow cancer-derived transcripts implicated in therapy resistance.

METHOD: The isolated platelet population of blood samples and digital-PCR were used to identify selected biomarker transcripts in patients with CRPC prior chemo- or androgen synthesis inhibiting therapy.

RESULTS: Fifty patients received either docetaxel (n = 24) or abiraterone (n = 26) therapy, with therapy response rates of 54% and 48%, respectively. Transcripts for the PC-associated biomarkers kallikrein-related peptidase-2 and -3 (KLK2, KLK3), folate hydrolase 1 (FOLH1), and neuropeptide-Y (NPY) were uniquely present within the platelet fraction of cancer patients and not detected in healthy controls (n = 15). In the abiraterone treated cohort, the biomarkers provided information on therapy outcome, demonstrating an association between detectable biomarkers and short progression free survival (PFS) (FOLH1, P < 0.01; KLK3, P < 0.05; and NPY, P < 0.05). Patients with biomarker-negative platelets had the best outcome, while FOLH1 (P < 0.05) and NPY (P = 0.05) biomarkers provided independent predictive information in a multivariate analysis regarding PFS. KLK2 (P < 0.01), KLK3 (P < 0.001), and FOLH1 (P < 0.05) biomarkers were associated with short overall survival (OS). Combining three biomarkers in a panel (KLK3, FOLH1, and NPY) made it possible to separate long-term responders from short-term responders with 87% sensitivity and 82% specificity.

CONCLUSION: Analyzing tumor-derived biomarkers in platelets of CRPC patients enabled prediction of the outcome after abiraterone therapy with higher accuracy than baseline serum PSA or PSA response.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2018
Keywords
biomarkers, liquid biopsy, personalized medicine, platelet, prostate cancer, therapy stratification
National Category
Cancer and Oncology Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-142384 (URN)10.1002/pros.23443 (DOI)000417131400007 ()29094381 (PubMedID)2-s2.0-85037377941 (Scopus ID)
Available from: 2017-11-29 Created: 2017-11-29 Last updated: 2023-03-24Bibliographically approved
Best, M. G., Sol, N., 't Veld, S. G. J., Vancura, A., Muller, M., Niemeijer, A.-L. N., . . . Wurdinger, T. (2017). Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets. Cancer Cell, 32(2), 238-252
Open this publication in new window or tab >>Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets
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2017 (English)In: Cancer Cell, ISSN 1535-6108, E-ISSN 1878-3686, Vol. 32, no 2, p. 238-252Article in journal (Refereed) Published
Abstract [en]

Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92-0.96; p < 0.001; n = 106 early-stage validation cohort, accuracy, 81%; AUC, 0.89; 95% CI, 0.83-0.95; p < 0.001), independent of age of the individuals, smoking habits, whole-blood storage time, and various inflammatory conditions. PSO enabled selection of gene panels to diagnose cancer from TEPs, suggesting that swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources.

Place, publisher, year, edition, pages
Elsevier, 2017
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-142881 (URN)10.1016/j.ccell.2017.07.004 (DOI)000407932500010 ()28810146 (PubMedID)2-s2.0-85027221443 (Scopus ID)
Available from: 2017-12-13 Created: 2017-12-13 Last updated: 2023-03-24Bibliographically approved
Tjon-Kon-Fat, L.-A., Köhn, L., Lundholm, M., Wurdinger, T., Thellenberg-Karlsson, C., Widmark, A., . . . Nilsson, J.Combining Circulating Biomarkers to Enhance Predictability of Therapy Response.
Open this publication in new window or tab >>Combining Circulating Biomarkers to Enhance Predictability of Therapy Response
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(English)Manuscript (preprint) (Other academic)
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-146051 (URN)
Available from: 2018-03-27 Created: 2018-03-27 Last updated: 2018-06-09
Tjon-Kon-Fat, L.-A., Köhn, L., Best, M., In't Velt, S., Lundholm, M., Thellenberg-Karlsson, C., . . . Nilsson, J.Detection of Early Stage Prostate Cancer Using Tumor Educated Platelet Profile Support Vector Machine (SVM) - Classification Algorithms.
Open this publication in new window or tab >>Detection of Early Stage Prostate Cancer Using Tumor Educated Platelet Profile Support Vector Machine (SVM) - Classification Algorithms
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(English)Manuscript (preprint) (Other academic)
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-146052 (URN)
Available from: 2018-03-27 Created: 2018-03-27 Last updated: 2018-06-09
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