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Uhlen, M., Karlsson, M. J., Zhong, W., Tebani, A., Pou, C., Mikes, J., . . . Brodin, P. (2019). A genome-wide transcriptomic analysis of protein-coding genes in human blood cells. Science, 366(6472), 1471-+, Article ID eaax9198.
Open this publication in new window or tab >>A genome-wide transcriptomic analysis of protein-coding genes in human blood cells
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2019 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 366, no 6472, p. 1471-+, article id eaax9198Article in journal (Refereed) Published
Abstract [en]

Blood is the predominant source for molecular analyses in humans, both in clinical and research settings. It is the target for many therapeutic strategies, emphasizing the need for comprehensive molecular maps of the cells constituting human blood. In this study, we performed a genome-wide transcriptomic analysis of protein-coding genes in sorted blood immune cell populations to characterize the expression levels of each individual gene across the blood cell types. All data are presented in an interactive, open-access Blood Atlas as part of the Human Protein Atlas and are integrated with expression profiles across all major tissues to provide spatial classification of all protein-coding genes. This allows for a genome-wide exploration of the expression profiles across human immune cell populations and all major human tissues and organs.

Place, publisher, year, edition, pages
AMER ASSOC ADVANCEMENT SCIENCE, 2019
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-402392 (URN)10.1126/science.aax9198 (DOI)000503861000045 ()31857451 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationKnut and Alice Wallenberg FoundationSwedish Research CouncilSwedish National Infrastructure for Computing (SNIC)Novo NordiskScience for Life Laboratory - a national resource center for high-throughput molecular bioscienceSwedish National Infrastructure for Computing (SNIC)
Available from: 2020-01-23 Created: 2020-01-23 Last updated: 2020-01-23Bibliographically approved
Månberg, A., Bradley, F., Qundos, U., Guthrie, B. L., Birse, K., Noel-Romas, L., . . . Broliden, K. (2019). A High-throughput Bead-based Affinity Assay Enables Analysis of Genital Protein Signatures in Women At Risk of HIV Infection. Molecular & Cellular Proteomics, 18(3), 461-476
Open this publication in new window or tab >>A High-throughput Bead-based Affinity Assay Enables Analysis of Genital Protein Signatures in Women At Risk of HIV Infection
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2019 (English)In: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 18, no 3, p. 461-476Article in journal (Refereed) Published
Abstract [en]

Women at high risk of HIV infection, including sex workers and those with active genital inflammation, have molecular signatures of immune activation and epithelial barrier remodeling in samples of their genital mucosa. These alterations in the local immunological milieu are likely to impact HIV susceptibility. We here analyze host genital protein signatures in HIV uninfected women, with high frequency of condom use, living in HIV-serodiscordant relationships. Cervicovaginal secretions from women living in HIV-serodiscordant relationships (n = 62) were collected at three time points over 12 months. Women living in HIV-negative seroconcordant relationships (controls, n = 25) were sampled at one time point. All study subjects were examined for demographic parameters associated with susceptibility to HIV infection. The cervicovaginal samples were analyzed using a high-throughput bead-based affinity assay. Proteins involved in epithelial barrier function and inflammation were increased in HIV-serodiscordant women. By combining several methods of analysis, a total of five proteins (CAPG, KLK10, SPRR3, elafin/PI3, CSTB) were consistently associated with this study group. Proteins analyzed using the affinity set-up were further validated by label-free tandem mass spectrometry in a partially overlapping cohort with concordant results. Women living in HIV-serodiscordant relationships thus had elevated levels of proteins involved in epithelial barrier function and inflammation despite low prevalence of sexually transmitted infections and a high frequency of safe sex practices. The identified proteins are important markers to follow during assessment of mucosal HIV susceptibility factors and a high-throughput bead-based affinity set-up could be a suitable method for such evaluation.

Place, publisher, year, edition, pages
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2019
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-385580 (URN)10.1074/mcp.RA118.000757 (DOI)000467885100006 ()30504243 (PubMedID)
Funder
Swedish Research CouncilVinnovaKnut and Alice Wallenberg Foundation
Available from: 2019-06-17 Created: 2019-06-17 Last updated: 2019-06-17Bibliographically approved
Eriksson, P., Lindskog, C., Lorente-Leal, V., Waldenström, J., González-Acuna, D., Järhult, J. D., . . . Ellström, P. (2019). Attachment Patterns of Human and Avian Influenza Viruses to Trachea and Colon of 26 Bird Species: Support for the Community Concept. Frontiers in Microbiology, 10, Article ID 815.
Open this publication in new window or tab >>Attachment Patterns of Human and Avian Influenza Viruses to Trachea and Colon of 26 Bird Species: Support for the Community Concept
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2019 (English)In: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 10, article id 815Article in journal (Refereed) Published
Abstract [en]

Avian influenza A viruses (AIVs) have a broad host range, but are most intimately associated with waterfowl (Anseriformes) and, in the case of the H13 and H16 subtypes, gulls (Charadriiformes). Host associations are multifactorial, but a key factor is the ability of the virus to bind host cell receptors and thereby initiate infection. The current study aims at investigating the tissue attachment pattern of a panel of AIVs, comprising H3N2, H6N1, H12N5, and H16N3, to avian trachea and colon tissue samples obtained from host species of different orders. Virus attachment was not restricted to the bird species or order from which the virus was isolated. Instead, extensive virus attachment was observed to several distantly related avian species. In general, more virus attachment and receptor expression were observed in trachea than in colon samples. Additionally, a human seasonal H3N2 virus was studied. Unlike the studied AIVs, this virus mainly attached to tracheae from Charadriiformes and a very limited set of avian cola. In conclusion, the reported results highlight the importance of AIV attachment to trachea in many avian species. Finally, the importance of chickens and mallards in AIVs dynamics was illustrated by the abundant AIV attachment observed.

Keywords
virus histochemistry, lectin staining, pattern of virus attachment, avian influenza, birds
National Category
Microbiology
Identifiers
urn:nbn:se:uu:diva-382841 (URN)10.3389/fmicb.2019.00815 (DOI)000464963200002 ()31057520 (PubMedID)
Funder
Swedish Research Council, 2015-03877Swedish Research Council, 2016-02596Knut and Alice Wallenberg Foundation
Note

De 2 första författarna delar förstaförfattarskapet.

Available from: 2019-05-22 Created: 2019-05-22 Last updated: 2019-10-24Bibliographically approved
Pineau, C., Hikmet, F., Zhang, C., Oksvold, P., Chen, S., Fagerberg, L., . . . Lindskog, C. (2019). Cell Type-Specific Expression of Testis Elevated Genes Based on Transcriptomics and Antibody-Based Proteomics. Journal of Proteome Research, 18(12), 4215-4230
Open this publication in new window or tab >>Cell Type-Specific Expression of Testis Elevated Genes Based on Transcriptomics and Antibody-Based Proteomics
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2019 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 18, no 12, p. 4215-4230Article in journal (Refereed) Published
Abstract [en]

One of the most complex organs in the human body is the testis, where spermatogenesis takes place. This physiological process involves thousands of genes and proteins that are activated and repressed, making testis the organ with the highest number of tissue-specific genes. However, the function of a large proportion of the corresponding proteins remains unknown and testis harbors many missing proteins (MPs), defined as products of protein-coding genes that lack experimental mass spectrometry evidence. Here, an integrated omits approach was used for exploring the cell type-specific protein expression of genes with an elevated expression in testis. By combining genome-wide transcriptomics analysis with immunohistochemistry, more than 500 proteins with distinct testicular protein expression patterns were identified, and these were selected for in-depth characterization of their in situ expression in eight different testicular cell types. The cell type-specific protein expression patterns allowed us to identify six distinct clusters of expression at different stages of spermatogenesis. The analysis highlighted numerous poorly characterized proteins in each of these clusters whose expression overlapped with that of known proteins involved in spermatogenesis, including 85 proteins with an unknown function and 60 proteins that previously have been classified as MPs. Furthermore, we were able to characterize the in situ distribution of several proteins that previously lacked spatial information and cell type specific expression within the testis. The testis elevated expression levels both at the RNA and protein levels suggest that these proteins are related to testis-specific functions. In summary, the study demonstrates the power of combining genome-wide transcriptomics analysis with antibody-based protein profiling to explore the cell type-specific expression of both well-known proteins and MPs. The analyzed proteins constitute important targets for further testis-specific research in male reproductive disorders.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2019
Keywords
testis, reproduction, spermatogenesis, antibody-based proteomics, missing proteins, protein evidence, immunohistochemistry, transcriptomics
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-400735 (URN)10.1021/acs.jproteome.9b00351 (DOI)000502164100015 ()31429579 (PubMedID)
Funder
Knut and Alice Wallenberg Foundation
Available from: 2020-01-17 Created: 2020-01-17 Last updated: 2020-01-17Bibliographically approved
Zhao, Z., Kurimchak, A., Nikonova, A. S., Feiser, F., Wasserman, J. S., Fowle, H., . . . Grana, X. (2019). PPP2R2A prostate cancer haploinsufficiency is associated with worse prognosis and a high vulnerability to B55 alpha/PP2A reconstitution that triggers centrosome destabilization. Oncogenesis, 8, Article ID 72.
Open this publication in new window or tab >>PPP2R2A prostate cancer haploinsufficiency is associated with worse prognosis and a high vulnerability to B55 alpha/PP2A reconstitution that triggers centrosome destabilization
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2019 (English)In: Oncogenesis, E-ISSN 2157-9024, Vol. 8, article id 72Article in journal (Refereed) Published
Abstract [en]

The PPP2R2A gene encodes the B55 alpha regulatory subunit of PP2A. Here, we report that PPP2R2A is hemizygously lost in similar to 42% of prostate adenocarcinomas, correlating with reduced expression, poorer prognosis, and an increased incidence of hemizygous loss (>75%) in metastatic disease. Of note, PPP2R2A homozygous loss is less common (5%) and not increased at later tumor stages. Reduced expression of B55 alpha is also seen in prostate tumor tissue and cell lines. Consistent with the possibility that complete loss of PPP2R2A is detrimental in prostate tumors, PPP2R2A deletion in cells with reduced but present B55 alpha reduces cell proliferation by slowing progression through the cell cycle. Remarkably, B55 alpha-low cells also appear addicted to lower B55 alpha expression, as even moderate increases in B55 alpha expression are toxic. Reconstitution of B55 alpha expression in prostate cancer (PCa) cell lines with low B55 alpha expression reduces proliferation, inhibits transformation and blocks xenograft tumorigenicity. Mechanistically, we show B55 alpha reconstitution reduces phosphorylation of proteins essential for centrosomal maintenance, and induces centrosome collapse and chromosome segregation failure; a first reported link between B55 alpha/PP2A and the vertebrate centrosome. These effects are dependent on a prolonged metaphase/anaphase checkpoint and are lethal to PCa cells addicted to low levels of B55 alpha. Thus, we propose the reduction in B55 alpha levels associated with hemizygous loss is necessary for centrosomal integrity in PCa cells, leading to selective lethality of B55 alpha reconstitution. Such a vulnerability could be targeted therapeutically in the large pool of patients with hemizygous PPP2R2A deletions, using pharmacologic approaches that enhance PP2A/B55 alpha activity.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-401173 (URN)10.1038/s41389-019-0180-9 (DOI)000502864500001 ()31822657 (PubMedID)
Available from: 2020-01-07 Created: 2020-01-07 Last updated: 2020-01-07Bibliographically approved
Edlund, K., Madjar, K., Mattsson, J. S., Djureinovic, D., Lindskog, C., Brunnström, H., . . . Hengstler, J. G. (2019). Prognostic Impact of Tumor Cell Programmed Death Ligand 1 Expression and Immune Cell Infiltration in NSCLC. Journal of Thoracic Oncology, 14(4), 628-640, Article ID S1556-0864(19)30009-7.
Open this publication in new window or tab >>Prognostic Impact of Tumor Cell Programmed Death Ligand 1 Expression and Immune Cell Infiltration in NSCLC
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2019 (English)In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 14, no 4, p. 628-640, article id S1556-0864(19)30009-7Article in journal (Refereed) Published
Abstract [en]

Introduction: Infiltration of T and B/plasma cells has been linked to NSCLC prognosis, but this has not been thoroughly investigated in relation to the expression of programmed death ligand 1 (PD-L1). Here, we determine the association of lymphocytes and PD-L1 with overall survival (OS) in two retrospective cohorts of operated NSCLC patients who were not treated with checkpoint inhibitors targeting the programmed death 1/PD-L1 axis. Moreover, we evaluate how PD-L1 positivity and clinicopathologic factors affect the prognostic association of lymphocytes.

Methods: Cluster of differentiation (CD) 3 (CD3)-, CD8-, CD4-, forkhead box P3 (FOXP3)-, CD20-, CD79A-, and immunoglobulin kappa constant (IGKC)-positive immune cells, and tumor PD-L1 positivity, were determined by immunohistochemistry on tissue microarrays (n = 705). Affymetrix data was analyzed for a patient subset, and supplemented with publicly available transcriptomics data (N = 1724). Associations with OS were assessed by Kaplan-Meier plots and uni- and multivariate Cox regression.

Results: Higher levels of T and B plasma cells were associated with longer OS (p = 0.004 and p < 0.001, for CD8 and IGKC, respectively). Highly proliferative tumors with few lymphocytes had the worst outcome. No association of PD-L1 positivity with OS was observed in a nonstratified patient population; however, a significant association with shorter OS was observed in never-smokers (p = 0.009 and p = 0.002, 5% and 50% cutoff). Lymphocyte infiltration was not associated with OS in PD-L1–positive tumors (50% cutoff). The prognostic association of lymphocyte infiltration also depended on the patients’ smoking history and histologic subtype.

Conclusions: Proliferation, PD-L1 status, smoking history, and histology should be considered if lymphocyte infiltration is to be used as a prognostic biomarker.

Keywords
Adenocarcinoma, Ki67, Lymphocyte, Prognosis, Squamous cell carcinoma
National Category
Clinical Laboratory Medicine Cell and Molecular Biology
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-380592 (URN)10.1016/j.jtho.2018.12.022 (DOI)000462167700021 ()30639618 (PubMedID)
Funder
Swedish Cancer Society, 15 0831
Available from: 2019-03-29 Created: 2019-03-29 Last updated: 2020-01-03Bibliographically approved
Elfving, H., Mattsson, J. S., Lindskog, C., Backman, M., Menzel, U. & Micke, P. (2019). Programmed Cell Death Ligand 1 Immunohistochemistry: A Concordance Study Between Surgical Specimen, Biopsy, and Tissue Microarray. Clinical Lung Cancer, 20(4), 258-262.e1
Open this publication in new window or tab >>Programmed Cell Death Ligand 1 Immunohistochemistry: A Concordance Study Between Surgical Specimen, Biopsy, and Tissue Microarray
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2019 (English)In: Clinical Lung Cancer, ISSN 1525-7304, E-ISSN 1938-0690, Vol. 20, no 4, p. 258-262.e1Article in journal (Refereed) Published
Abstract [en]

Programmed cell death ligand 1 (PD-L1) expression within the same lung cancer tissue is variable. In this study we evaluated if the PD-L1 expression on small biopsy specimens represent the PD-L1 status of the corresponding resection specimen. Our results indicate a relative good agreement between biopsy and surgical specimens, with a discordance in approximately 10% of the cases. Background: The immunohistochemical analysis of programmed cell death ligand 1 (PD-L1) expression in tumor tissue of non-small-cell lung cancer patients has now been integrated in the diagnostic workup. Analysis is commonly done on small tissue biopsy samples representing a minimal fraction of the whole tumor. The aim of the study was to evaluate the correlation of PD-L1 expression on biopsy specimens with corresponding resection specimens. Materials and Methods: In total, 58 consecutive cases with preoperative biopsy and resected tumor specimens were selected. From each resection specimen 2 tumor cores were compiled into a tissue microarray (TMA). Immunohistochemical staining with the antibody SP263 was performed on biopsy specimens, resection specimens (whole sections), as well as on the TMA. Results: The proportion of PD-L1-positive stainings were comparable between the resection specimens (48% and 19%), the biopsies (43% and 17%), and the TMAs (47% and 14%), using cutoffs of 1% and 50%, respectively (P > .39 all comparisons). When the resection specimens were considered as reference, PD-L1 status differed in 16%/5% for biopsies and in 9%/9% for TMAs (1%/50% cutoff). The sensitivity of the biopsy analysis was 79%/82% and the specificity was 90%/98% at the 1%/50% cutoff. The Cohens kappa value for the agreement between biopsy and tumor. was 0.70 at the 1% cutoff and 0.83 at the 50% cutoff. Conclusion: The results indicate a moderate concordance between the analysis of biopsy and whole tumor tissue, resulting in misclassification of samples in particular when the lower 1% cutoff was used. Clinicians should be aware of this uncertainty when interpreting PD-L1 reports for treatment decisions.

Keywords
Checkpoint inhibitors, Nivolumab, PD-1, PD-L1, Pembrolizumab
National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-390976 (URN)10.1016/j.cllc.2019.02.012 (DOI)000475296800018 ()30926355 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2019-08-16 Created: 2019-08-16 Last updated: 2020-01-03Bibliographically approved
Uhlen, M., Karlsson, M. J., Hober, A., Svensson, A.-S., Scheffel, J., Kotol, D., . . . Sivertsson, A. (2019). The human secretome. Science Signaling, 12(609), Article ID eaaz0274.
Open this publication in new window or tab >>The human secretome
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2019 (English)In: Science Signaling, ISSN 1945-0877, E-ISSN 1937-9145, Vol. 12, no 609, article id eaaz0274Article in journal (Refereed) Published
Abstract [en]

The proteins secreted by human cells (collectively referred to as the secretome) are important not only for the basic understanding of human biology but also for the identification of potential targets for future diagnostics and therapies. Here, we present a comprehensive analysis of proteins predicted to be secreted in human cells, which provides information about their final localization in the human body, including the proteins actively secreted to peripheral blood. The analysis suggests that a large number of the proteins of the secretome are not secreted out of the cell, but instead are retained intracellularly, whereas another large group of proteins were identified that are predicted to be retained locally at the tissue of expression and not secreted into the blood. Proteins detected in the human blood by mass spectrometry-based proteomics and antibody-based immuno-assays are also presented with estimates of their concentrations in the blood. The results are presented in an updated version 19 of the Human Protein Atlas in which each gene encoding a secretome protein is annotated to provide an open-access knowledge resource of the human secretome, including body-wide expression data, spatial localization data down to the single-cell and subcellular levels, and data about the presence of proteins that are detectable in the blood.

Place, publisher, year, edition, pages
AMER ASSOC ADVANCEMENT SCIENCE, 2019
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-400051 (URN)10.1126/scisignal.aaz0274 (DOI)000499099300003 ()31772123 (PubMedID)
Funder
Knut and Alice Wallenberg Foundation
Available from: 2019-12-18 Created: 2019-12-18 Last updated: 2019-12-18Bibliographically approved
Niinivirta, M., Enblad, G., Lindskog, C., Pontén, F., Dragomir, A. & Ullenhag, G. (2019). Tumoral pyruvate kinase L/R as a predictive marker for the treatment of renal cancer patients with sunitinib and sorafenib. Journal of Cancer, 10(14), 3224-3231
Open this publication in new window or tab >>Tumoral pyruvate kinase L/R as a predictive marker for the treatment of renal cancer patients with sunitinib and sorafenib
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2019 (English)In: Journal of Cancer, ISSN 1837-9664, Vol. 10, no 14, p. 3224-3231Article in journal (Other academic) Published
Abstract [en]

Background and aims: Treatment with tyrosine kinase inhibitors (TKI) like sunitinib and sorafenib has improved the prognosis of patients with metastatic renal cell cancer (mRCC). No predictive marker is available to select patients who will gain from these treatments. Tumoral pyruvate kinase L/R (PKLR) is a membrane protein with highly specific expression in the renal tubule. We have previously shown that the tumoral expression of cubilin (CUBN) is associated with progression free survival (PFS) in mRCC patients treated with sunitinib and sorafenib. The aim of the present study was to investigate if PKLR can predict response in these patients, alone and/or in combination with CUBN.

Methods: A tissue microarray (TMA) was constructed of tumor samples from 139 mRCC patients. One hundred and thirty-six of these patients had been treated with sunitinib or sorafenib in the first or second-line setting. Thirty patients suffered from early severe toxicity leading to the termination of treatment. The remaining patients (n=106) were selected for the current study.

Results: Fifty-five (52%) of the tumors expressed membranous PKLR. Patients with PKLR tumor expression experienced a significantly longer PFS compared to patients with no expression (eight versus five months, p = 0.019). Overall survival (OS) was also significantly better for patients with PKLR expression. In addition, the combined expression of PKLR and CUBN resulted in a higher predictive value than either marker alone.

Conclusions: In this real world study we show that tumoral PKLR membrane expression is a positive predictive biomarker for sunitinib and sorafenib treatment in patients suffering from mRCC. Our results also indicate that the combined expression with cubilin more accurately than PKLR alone can select patients with no benefit from treatment.

National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Oncology; Pathology
Identifiers
urn:nbn:se:uu:diva-360611 (URN)10.7150/jca.30130 (DOI)000470088200017 ()
Funder
Knut and Alice Wallenberg Foundation
Available from: 2018-09-16 Created: 2018-09-16 Last updated: 2020-01-08Bibliographically approved
Miyashita, N., Horie, M., Suzuki, H. I., Yoshihara, M., Djureinovic, D., Persson, J., . . . Nagase, T. (2018). An Integrative Analysis of Transcriptome and Epigenome Features of ASCL1-Positive Lung Adenocarcinomas. Journal of Thoracic Oncology, 13(11), 1676-1691
Open this publication in new window or tab >>An Integrative Analysis of Transcriptome and Epigenome Features of ASCL1-Positive Lung Adenocarcinomas
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2018 (English)In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 13, no 11, p. 1676-1691Article in journal (Refereed) Published
Abstract [en]

Introduction: A subgroup of lung adenocarcinoma shows neuroendocrine differentiation and expression of achaete-scute family bHLH transcription factor 1 (ASCL1), common to high-grade neuroendocrine tumors, small-cell lung cancer and large cell neuroendocrine carcinoma. Methods: The aim of this study was to characterize clinical and molecular features of ASCL1-positive lung adenocarcinoma by using recent transcriptome profiling in multiple patient cohorts and genome-wide epigenetic profiling including data from The Cancer Genome Atlas. Results: The ASCL1-positive subtype of lung adenocarcinoma developed preferentially in current or former smokers and usually did not harbor EGFR mutations. In transcriptome profiling, this subtype overlapped with the recently proposed proximal-proliferative molecular subtype. Gene expression profiling of ASCL1-positive cases suggested generally poor immune cell infiltration and none of the tumors were positive for programmed cell death ligand 1 protein expression. Genome-wide methylation analysis showed global DNA hypomethylation in ASCL1-positive cases. ASCL1 was associated with super-enhancers in ASCL1-positive lung adenocarcinoma cells, and ASCL1 silencing suppressed other super-enhancer-associated genes, suggesting thatASCL1 acts as a master transcriptional regulator. This was further reinforced by the essential roles of ASCL1 in cell proliferation, survival, and cell cycle control. Conclusions: These results suggest that ASCL1 defines a subgroup of lung adenocarcinoma with distinct molecular features by driving super-enhancer-mediated transcriptional programs.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2018
Keywords
Lung cancer, Adenocarcinoma, Neuroendocrine, ASCL1, NSCLC
National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-371088 (URN)10.1016/j.jtho.2018.07.096 (DOI)000450088600020 ()30121393 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationSwedish Cancer Society
Available from: 2018-12-19 Created: 2018-12-19 Last updated: 2019-03-29Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-5611-1015

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