Highlighted Publications

Anssi Auvinen | Epidemiology

 

 

A randomized trial of early detection of clinically significant prostate cancer.

Describes the rationale and design of the population-based ProScreen trial combining PSA kallikrein panel (4Kscore) and MRI for prostate cancer screening, with the aim of assessing the extent of overdiagnosis (detection of clinically insignificant cancer) as well as prostate cancer mortality as the main end-point

Auvinen A, Rannikko A, Taari K, Kujala P, Mirtti T, Kenttämies A, Rinta-Kiikka I, Lehtimäki T, Oksala N, Pettersson K, Tammela TL.
Eur JU Epid 2017;32: 521-527

Auvinen et al. – 2017 – A randomized trial of early detection of clinicall


Steven Bova | PELICAN-Personalized Cancer Medicine

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Prostate cancer evolution from multilineage primary to single lineage metastases with implications for liquid biopsy

We infer detailed reconstructions of tumor phylogenies in ten prostate cancer patients with fatal disease and investigate them in conjunction with histopathology and tumor DNA extracted from blood and cerebrospinal fluid. One dominant lineage emerges that initiates and drives systemic metastasis. Routes to metastasis differ between patients, and likely genetic drivers of metastasis distinguish the metastatic lineage from the lineage that remains confined to the prostate. Body fluids capture features of the dominant lineage, and subclonal expansions that occur in the metastatic phase are non-uniformly represented. Cerebrospinal fluid analysis reveals lineages not detected in blood-borne DNA, suggesting possible clinical utility.

Link to whole article: https://rdcu.be/b8eoZ

Woodcock DJ, Riabchenko E, Taavitsainen S, Kankainen M, Gundem G, Brewer DS, Ellonen P, Lepistö M, Golubeva YG, Warner AC, Tolonen TT, Jasu J, Isaacs WB, Emmert-Buck MR, Nykter M, Visakorpi T, Bova GS, Wedge DC.

Nat Commun. 2020 Oct 8;11(1):5070

Woodcock et al. – 2020 – Prostate cancer evolution from multilineage primar


Frank Emmert-Streib | Predictive Society and Data Analytics Lab

 

 

Prostate Cancer Gene Regulatory Network Inferred from RNA-Seq Data

Prostate cancer is a complex disease that can only be understood by interrogating the regulatory elements among genes and proteins. In this paper we inferred a prostate cancer Gene Regulatory Network (GRN) from a gene expression data set of patient RNA-seq profiles obtained from The Cancer Genome Atlas (TCGA) database. Our network-based analysis provides a practical systems biology approach for revealing large-scale interactions of prostate cancer. This allows a close interpretation of biological activities in terms of the hallmarks of cancer.

Daniel Moore, Ricardo de Matos Simoes, Matthias Dehmer, Frank Emmert-Streib

Curr Genomics. 2019 20(1):38-48.

Moore et al. – 2019 – Prostate Cancer Gene Regulatory Network Inferred f


Kirsi Granberg | Cancer Regulation and Immunology

 

 

Tumor immune microenvironment analysis reveals three tumor subgroups

Understanding the nature of immunosuppression in malignant tissue is important for successful cancer treatment through immune system modulation. In this study, we uncovered high variability in immune system-related responses and in the composition of the microenvironment across glioblastoma (GBM) cohort, suggesting immunologic diversity. Our analysis identified three GBM subgroups presenting different adaptive immune responses: negative, humoral, and cellular-like. These subgroups and immune cell compositions were associated with typical alterations, such as CDK4 amplifications or inactivating NF1 alterations. All IDH-mutated samples were in the negative group, and they showed lower expression and higher DNA methylation of MHC-I genes.

Luoto S, Hermelo I, Vuorinen E, Hannus P, Kesseli J, Nykter M, Granberg KJ

Cancer Res. 2018 78(19):5574-5585.

Luoto et al. – 2018 – Computational Characterization of Suppressive Immu


Teemu Murtola | Pharmacoepidemiology and Chemoprevention

 

 

Atorvastatin Versus Placebo for Prostate Cancer Before Radical Prostatectomy-A Randomized, Double-blind, Placebo-controlled Clinical Trial

We tested whether intervention with atorvastatin affects the prostate beneficially compared with placebo in men with prostate cancer in a randomized clinical trial. A total of 160 statin-naïve prostate cancer patients scheduled for radical prostatectomy were randomized to use 80 mg atorvastatin or placebo daily from recruitment to surgery for a median of 27 d. Cholesterol-lowering atorvastatin does not lower prostate cancer proliferation rate compared with placebo overall, but exploratory analyses suggest a benefit in longer exposure.

Murtola TJ, Syvälä H, Tolonen T, Helminen M, Riikonen J, Koskimäki J, Pakarainen T, Kaipia A, Isotalo T, Kujala P, Tammela TLJ.

Eur Urol. 274:697-701, 2018.

 


Matti Nykter | Computational Biology

 

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Integrative proteogenomics in prostate cancer

We report high-throughput mass spectrometry with integrated genome level analysis on clinical tissue samples of benign prostatic hyperplasia (BPH), untreated primary prostate cancer (PC) and castration resistant prostate cancer (CRPC). Each sample group shows a distinct protein profile. We show that, especially in CRPC, gene copy number, DNA methylation, and RNA expression levels do not reliably predict proteomic changes. Instead, we uncover previously unrecognized molecular and pathway events, for example, several miRNA target correlations present at protein but not at mRNA level. Notably, we identify two metabolic shifts in the citric acid cycle (TCA cycle) during prostate cancer development and progression.

See Research highlight article “Controlling Mutational Chaos” in Nature Reviews Urology.
https://www.nature.com/articles/s41585-018-0021-1

Latonen et al. – 2018 – Integrative proteomics in prostate cancer uncovers


Pekka Ruusuvuori | Bioimage Informatics

 

 

Artificial intelligence for diagnosis and grading of prostate cancer in biopsies

We report pathologist level accuracy for artificial intelligence based detection, length estimation and grading of prostate cancer from histopathological images in a population based diagnostic study in a collaboration study led by researchers at Karolinska Institutet.

https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30738-7/fulltext

Ström, P., Kartasalo, K., Olsson, H., Solorzano, L., Delahunt, B., Berney, D. M.,  Iczkowski, K. A., Kench, J.G., Kristiansen, G., van der Kwast, T.H., Leite, K.R.M., McKenney, J.K., Oxley, J., Pan, C., Samaratunga, H., Srigley, J.R., Takahashi, H., Tsuzuki, T., Varma, M., Zhou, M., Lindberg, J., Lindskog, C., Ruusuvuori, P., Wählby, C., Grönberg, H., Rantalainen, M., Egevad, L., Eklund M. (2020).

Artificial intelligence for diagnosis and grading of prostate cancer in biopsies: a population-based, diagnostic study.

The Lancet Oncology, 21(2), 222-232.

Ström et al. – 2020 – Artificial intelligence for diagnosis and grading_


Johanna Schleutker | Genetic Predisposition to Prostate Cancer

 

 

Implications of the 19q13 Aggressive Prostate Cancer Susceptibility Locus

We found an association of the aggressive PCa-associated allele G of rs11672691 with elevated transcript levels of two biologically plausible candidate genes, PCAT19 and CEACAM21, implicated in PCa cell growth and tumor progression. Mechanistically, rs11672691 resides in an enhancer element and alters the binding site of HOXA2, a novel oncogenic transcription factor with prognostic potential in PCa. Remarkably, CRISPR/Cas9-mediated single-nucleotide editing showed the direct effect of rs11672691 on PCAT19 and CEACAM21 expression and PCa cellular aggressive phenotype. Clinical data demonstrated synergistic effects of rs11672691 genotype and PCAT19/CEACAM21 gene expression on PCa prognosis.

Gao P, Xia JH, Sipeky C, Dong XM, Zhang Q, Yang Y, Zhang P, Cruz SP, Zhang K, Zhu J, Lee HM, Suleman S, Giannareas N, Liu S; PRACTICAL Consortium, Tammela TLJ, Auvinen A, Wang X, Huang Q, Wang L, Manninen A, Vaarala MH, Wang L, Schleutker J, Wei GH.
Cell 174(3):576-589, 2018

https://doi.org/10.1016/j.cell.2018.06.003


Teuvo Tammela | Molecular Biology

 

 

Nonmetastatic Castration-Resistant Prostate Cancer and Survival with Darolutamide.

In this double-blind, placebo-controlled trial, we randomly assigned 1509 men, in a 2:1 ratio, to receive darolutamide (955 patients) or placebo (554 patients) while they continued to receive androgen-deprivation therapy. After the results of the primary end-point analysis were found to be positive, unblinding of the treatment assignments occurred, and patients in the placebo group were permitted to cross over to receive open-label darolutamide treatment.Among men with nonmetastatic, castration-resistant prostate cancer, the percentage of patients who were alive at 3 years was significantly higher among those who received darolutamide than among those who received placebo. The incidence of adverse events was similar in the two groups. (Funded by Bayer HealthCare and Orion Pharma; ARAMIS ClinicalTrials.gov number.

Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, Jievaltas M, Luz M, Alekseev B, Kuss I, Le Berre MA, Petrenciuc O, Snapir A, Sarapohja T, Smith MR; ARAMIS Investigators.

N Engl J Med. 2020 Sep 10;383(11):1040-1049.

Fizazi et al. – 2020 – Nonmetastatic Castration-Resistant Prostate Cance


Teemu Tolonen | Histopathology

 

 

Extraprostatic extension (pT3a) in prostate biopsy is an under-recognized feature indicating high risk disease

Extraprostatic extension (EPE+) in a needle biopsy may be more common than previously thought. Approximately one of six high grade prostate cancers harbor EPE+ in core biopsies. EPE+ is associated with highly adverse features of prostate cancer, making its reporting obligatory. More studies are needed to establish the predictive and prognostic value of EPE+ in needle biopsies

Tolonen TT, Riikonen J, Tammela TLJ, Koivusalo L, Haapasalo H, Kujala P, Kaipia A. Extraprostatic extension (pT3a) in prostate biopsy is an under-recognized feature indicating high risk disease.

Ann Diagn Pathol. 2018 Aug;35:80-84