Correction: High Keratin 8/18 Ratio Predicts Aggressive Hepatocellular Cancer Phenotype12 (vol 12, pg 256, 2019)

Corrigendum to High Keratin 8/

18 Ratio Predicts Aggressive

Hepatocellular Cancer

Phenotype12 [Translational

Oncology Volume 12, Issue 2,

February 2019, Pages 256-268]

N. Golob-Schwarzl*,†, K. Bettermann*,

A.K. Mehta*,‡, S.M. Kessler*, §, J. Unterluggauer*, S. Krassnig*, K. Kojima¶, X. Chen¶, Y. Hoshida¶, N.M. Bardeesy#, H. Müller*, V. Svendova**, M.G. Schimek**, C. Diwoky††,‡‡, A. Lipfert††, V. Mahajan*, C. Stumptner*, A. Thüringer*, L.F. Fröhlich*, §§, T. Stojakovic¶¶, K.P.R. Nilsson##, T. Kolbe***,†††, T. Rülicke‡‡‡, T.M. Magin§§§, P. Strnad¶¶¶, A.K. Kiemer†, R. Moriggl###, ****,†††† and Johannes Haybaeck*,‡‡‡‡

*_{Institute of Pathology, Medical University of Graz, Graz, Austria;}

†_{Center for Biomarker Research in Medicine, Graz, Austria;} ‡_{Department of Medical Oncology, Dana-Farber Cancer} Insti-tute, 450 Brookline Avenue, Boston, MA 02215, USA; §

Department of Pharmacy, Pharmaceutical Biology, Saarland University, Saarbrücken, Germany;¶Liver Tumor Translational Research Program, University of Texas Southwestern Medical Center, Dallas, USA;#_{Center for Cancer Research,}

Massachusetts General Hospital, Harvard Medical School, Boston, USA;**_{Institute for Medical Informatics, Statistics and} Documentation, Medical University of Graz, Graz, Austria; ††_{Institute of Medical Engineering, Graz University of}

Technology, Graz, Austria;‡‡Institute of Molecular Biosciences, University of Graz, Graz, Austria;§§AG VABOS, Department of Cranio-Maxillofacial Surgery, Univerity of Muenster, Germany; ¶¶

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria; ##

Department of Chemistry, Linköping University, Linköping, Sweden;***Biomodels Austria (Biat), University of Veterinary Medicine Vienna, Vienna, Austria;†††Department IFA-Tulln, University for Natural Resources and Applied Life Sciences Vienna, Vienna, Austria;‡‡‡Institute of Laboratory Animal Science, University of Veterinary Medicine Vienna, Vienna, Austria;§§§_{Institute of Biology, University of Leipzig, Leipzig,} Germany;¶¶¶Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany;###_{Institute of} Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria;****Ludwig Bolzmann Institute of Cancer Research, Vienna, Austria;††††Medical University Vienna, Vienna, Austria;‡‡‡‡Department of

Pathology, Medical Faculty, Otto-von-Guericke-University Mag-deburg, MagMag-deburg, Germany

The authors regretbinsert corrigendum textN.

The authors would like to apologize for any inconvenience caused. The authors regret that an error in Figure S1 of the manuscript has been identified. Some images in Figure 1 were duplicated within Figure S1; hence, this corrigendum addresses this error.

Following changes were made to improve the quality of the results section:

To further address the contribution of KRT8 and KRT18 with respect to liver pathology in livers of wild-type (wt), Krt8+/−, Krt8−/−, Krt18+/−, and Krt18−/−

www.transonc.com

Tr a n s l a t i o n a l

O n c o l o g y

Address all correspondence to: Johannes Haybaeck, MD, PhD, Department of Pathology, Otto-von-Guericke-University Magdeburg, Leipziger Straße 44, D-39120 Magdeburg, Germany. E-mail:Johannes.haybaeck@med.ovgu.de

© 2019 The Authors. Published by Elsevier Inc. on behalf of Neoplasia Press, Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).

mice aged 3 and 17-20 months, we performed, in addition to light microscopy, double immunofluorescence microscopy (DIF) using anti-bodies against K8/18 and p62. Moreover, heptameric oligothiophene, h-HTAA (Mahajan et al., 2011), was used to confirm ß-sheet conformation (Figure 1).

In livers of 6-month-old Krt18+/−and Krt18−/−mice, total FA amounts were significantly increased compared to wt mice (Figure 2, Figure S1, and Table S1). The following NAFLD-related mRNAs remained largely unchanged: Malonyl-CoA decarboxylase (Mlycd), Microsomal triglyceride transfer protein (Mttp), ATP-binding cassette, sub-family C, member 2 (Cftr/Mrp) (Figure

S2A), Insulin receptor substrate 1 (Isr1), Glutamate-cysteine ligase, modifier subunit (Gclm), Fatty acid synthase (Fasn) (Figure S2B), Diacylglycerol O-acyltransferase 2 (Dgat2), Angiotensin II receptor 1a (Agtr1α), Adiponectin receptor 2 (Adipor2) (Figure S2C) and Peroxisome proliferator activated receptor alpha (Pparα) (Figure S2D).

In addition, the following changes have been made in the discussion section

qRT-PCR analyses revealed a significant increase of Srebpb1 mRNA level in Krt18−/−mice aged 3 and 6 months, whereas no increased mRNA expression of Pparα was identified (Figure 3; Figure S2).

Figure S1. Total hepatic fatty acids and hepatic fatty acid profile of Krt8−/−and p62−/−livers.Total hepatic FAs were measured by GC-MS. (A) Analysis of total FAs shows a marked tendency of reduction in 6- and 12-month-old Krt8−/−_{animals compared to age-matched wt and} Krt8+/−mice. Estimation of the total FA content in 3- and 6-month-old p62−/−mice and their respective littermates reveals no significant changes (see also Table S2).(B) The livers of the different aged wt, Krt8+/−_{, and Krt8}−/−_{mice as well as the livers of the p62}−/−_{and their} respective wt controls show no significant changes in their profile (see also Table S2). Data are presented asμg/mg liver tissue, results are shown as mean, and error bars indicate SEM. *, **, and *** indicate statistical significance (Student’s t test): * = Pb.05; ** = Pb.001; *** = Pb.0001.

Figure S2. Transcriptional profile of wt, Krt18+/−, and Krt18−/−livers for NAFLD-related genes at various time points.qRT-PCR analysis for mRNA expression of candidate genes in murine livers at 3, 6, 12, and 18 month of age.(A) Expression levels of Mlycd, Mttp, Cftr/Mrp, (B) Isr1, Gclm, Fasn,(C) Dgat2, Agtr1, Adipor2, and (D) Ppar are indicated by symbols (circles for wt, squares for Krt18+/−, and triangles for Krt18−/−mice) and presented as fold change log10. Each data point reflects the expression of a particular gene resulting from three to six different mice, normalized to the mean expression value of the respective gene in wt livers. Results are shown as mean; error bars indicate SD. Significance values are described by asterisks above horizontal bars. *, **, *** indicate statistical significance (two-way ANOVA with Bonferroni posttest): * = P≤.05; ** = Pb.001; *** = Pb.0001.