This weekend, Carlo Croce had some reprieve from the misconduct accusations that have followed him for years (recently described in a lengthy article in the New York Times) and that have prompted his university to re-open an investigation. On Sunday, he received a prestigious award from the American Association for Cancer Research, honoring his work.
But the moment may have been short-lived. Today, Croce received two expressions of concern (EOCs) from PNAS for two well-cited papers published over a decade ago, on which Croce — chair of the Department of Cancer Biology and Genetics at The Ohio State University (OSU) — is last author. The two EOCs cite concerns over duplicated bands. What’s more, another journal recently decided to retract one of his papers, citing figures that didn’t represent the results of the experiments.
PNAS chose to issue EOCs, rather than retractions or corrections, because the authors didn’t agree that the bands were duplicated, according to executive editor Diane Sullenberger. She explained how the journal learned of the issues with the two papers:
After the New York Times contacted us about the allegations of image manipulation, we obtained two independent reports that found probable duplication of bands. High-resolution originals were not available because the papers were from 2003 and 2005.
According to the notices, the authors no longer possess the original data.
Last month, Croce and his colleague Alfredo Fusco, a cancer researcher in Italy, withdrew a 2012 paper in Journal of Biological Chemistry (JBC) on which they are middle authors —the sixth retraction for Croce and tenth for Fusco, by our count. Both researchers are currently under investigation for scientific misconduct by their respective institutions.
The notice describes concerns with several figures, which the authors could not address — again, due to a lack of original data. According to Kaoru Sakabe, data integrity manager at American Society for Biochemistry and Molecular Biology, which publishes JBC:
Three figures were at issue in this case. As is customary, we requested the original data for these figures. The authors were unable to provide the original data for Fig 1C, so they could not address our concerns. In addition, the other two figures, 2D and 6E, as it turns out, did not accurately represent the experimental conditions. Given the inaccuracies in 2D and 6E, plus the unanswered questions about 1C, the authors decided it would be best to withdraw the paper.
Here’s PNAS’s expression of concern for the 2003 paper, “Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25–q27,” signed by PNAS editor-in-chief Inder Verma:
The editors wish to note that Fig. 2a and 2b, β-actin panel, appears to have duplicated bands. The authors note that “because this issue was first raised more than 10 years after publication, the original data are not available to confirm whether an error was made in the figure construction.” However, the authors state that any error in figure construction does not affect their scientific conclusions.
Here’s the second, similarly worded, expression of concern notice for the 2005 article, “WWOX gene restoration prevents lung cancer growth in vitro and in vivo,” also signed by Verma:
The editors wish to note that Fig. 1B, β-actin panel, appears to have duplicated bands. The authors note that “because this issue was first raised more than 7 years after publication, the original data are not available to confirm whether an error was made in the figure construction.” However, the authors state that any error in figure construction does not affect their scientific conclusions. The authors have provided an image from a replicate experiment completed in 2014 which, the authors state, “confirms the results shown in Figure 1B. This confirmation supports the conclusions in this work.” The image for Fig. 1B and its legend appear below.
The 2003 and 2005 papers have been cited 151 and 100 times, respectively, according to Clarivate Analytics’ Web of Science, formerly part of Thomson Reuters.
And here’s the retraction notice for “POZ-, AT-hook-, and Zinc Finger-containing Protein (PATZ) Interacts with Human Oncogene B Cell Lymphoma 6 (BCL6) and Is Required for Its Negative Autoregulation,” published in 2012 and cited 15 times (once by a previous correction notice):
This article has been withdrawn by the authors. Figs. 2D and 6E did not accurately represent experimental conditions. Additionally, the journal raised concerns with regards to Fig. 1C. The authors were not able to provide the original data for this figure. The authors state that these inaccuracies in figure representation did not affect any of the scientific conclusions of the paper.
Croce is fourth to last author and Fusco is third to last author on the study.
Here’s the 2014 correction notice for the paper, which describes issues with a figure not featured in the retraction:
Western blot images representing PATZ, BCL6, and tubulin in Fig. 6C did not accurately represent the experimental results. Different lanes were erroneously duplicated. Lane 3 of the PATZ panel was duplicated in lane 7; lane 4 of the PATZ panel was duplicated in lanes 5 and 6; lane 1 of the BCL6 panel was duplicated in lane 2; lane 4 of the tubulin panel was duplicated in lane 7; and lane 5 of the tubulin panel was duplicated in lane 6. The authors have provided an image from a replicate experiment. This correction does not affect the interpretation or conclusions of this work.
We contacted Croce and the corresponding authors on the JBC paper—Monica Fedele and Lorenzo Chiariotti, both affiliated with the University of Naples, where Fusco is also affiliated.
Hat tip for JBC retraction: David Sanders
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Why isn’t image duplication an instant retraction-worthy sin? If the image is unimportant to the conclusions, then it doesn’t need to be there, and duplication should be pointless (there’s no reason to lie). The lie is sufficient in itself to kill the paper (readers can no longer trust your word or your evidence). If it is important (needed to strengthen conclusions, or as evidence for the primary claim), then the duplication affects the paper’s conclusions; as above, since readers can no longer trust your word or your evidence, the paper should be retracted.
I just got a negative decision for our manuscript from Clinical Cancer Research and then Leukemia. I wonder what would happen if we were more creative in data handling and duplicated some data and presented it as something else to explain the full mechanism, like many successful scientist that has a paper in the oven almost every week. There seem to be no problem if duplicated data is detected, just change it with something else from your drawer and stamp it with “This correction does not affect the interpretation or conclusions of this work”.
I did my graduate work at OSU (not in the Department of Cancer Biology and Genetics). My mentor was often frustrated with my ambiguous, “murky” data and unhappy that it wouldn’t get into high impact journals. The one way I could reliably calm him down was to say “At least you know I am not fabricating my data, because if I was, I would fabricate much better data than this.”
2017 corrigendum for
MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review
Marilena V. Iorio, Carlo M. Croce
Author Affiliations
Marilena V. Iorio1 and Carlo M. Croce ([email protected]) *,2
1Start Up Unit, Department of Experimental Oncology, Fondazione IRCCS, Istituto Nazionale Tumori, Milano, Italy
2Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA
↵*Tel: +1 614 292 3063; Fax: +1 614 292 4080
View Abstract
DOI 10.1002/emmm.201100209| Published online 20.02.2012
EMBO Molecular Medicine (2012) 4, 143-159
Corrigendum. http://embomolmed.embopress.org/content/9/6/852
This article, published in the March 2012 issue of EMBO Molecular Medicine, contained text passages similar to those from a number of previous publications, many by the same authors: “Cancer microRNAs: from subtype profiling to predictors of response to therapy” by Chan E, Pardo DE, Weidhaas JB in Trends Mol Med 17: 235–243; “Targeting microRNAs in cancer: rationale, strategies and challenges” by Garson R, Marcucci G, Croce CM in Nat Rev Drug Discov 9: 775–789; “MicroRNAs in cancer: small molecules with a huge impact” by Iorio MV, Croce CM in J Clin Oncol 27: 5848–5856; and “Breast cancer and microRNAs: therapeutic impact” by Iorio MV, Casalini P, Piovan C, Braccioli L, Tagliabue E in Breast 20 Suppl. 3: S63–S70. Formal citations to the original articles were inadvertently omitted.
Similarly, a number of later publications overlap with text from this reference without formal citations. These are as follows: “microRNA: new players in metastatic process” by Triulzi T, Iorio MV, Tagliabue E, Casalini P in Oncogene and cancer—from bench to clinic, Siregar Y (ed.), Chapter 16. Rijeka: InTech; “microRNA involvement in human cancer” by Iorio MV, Croce CM in Carcinogenesis 33: 1126–1133; and “Causes and consequences of microRNA dysregulation” by Iorio MV, Croce CM in Cancer J, 18: 215–222. The authors apologize for this oversight.
© 2017 The Authors
Figure 2 Oncogene 26:4148 (2007) and figure 1A PNAS 103:5078 (2006).
http://imgur.com/Y8y4mBi
https://pubpeer.com/publications/FD3FFAE9F5D5F86C04C5D7E6505BDA#4
For reference:-
1.Oncogene 26:4148.
Oncogene. 2007 Jun 14;26(28):4148-57. Epub 2007 Jan 29.
MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia.
Garzon R1, Pichiorri F, Palumbo T, Visentini M, Aqeilan R, Cimmino A, Wang H, Sun H, Volinia S, Alder H, Calin GA, Liu CG, Andreeff M, Croce CM.
Author information
Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.
2.PNAS 103:5078.
Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5078-83. Epub 2006 Mar 20.
MicroRNA fingerprints during human megakaryocytopoiesis.
Garzon R1, Pichiorri F, Palumbo T, Iuliano R, Cimmino A, Aqeilan R, Volinia S, Bhatt D, Alder H, Marcucci G, Calin GA, Liu CG, Bloomfield CD, Andreeff M, Croce CM.
Author information
1
Department of Molecular Virology, Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.
JAMA. 2011 Jan 5;305(1):59-67. doi: 10.1001/jama.2010.1919.
Association of a microRNA/TP53 feedback circuitry with pathogenesis and outcome of B-cell chronic lymphocytic leukemia.
Fabbri M1, Bottoni A, Shimizu M, Spizzo R, Nicoloso MS, Rossi S, Barbarotto E, Cimmino A, Adair B, Wojcik SE, Valeri N, Calore F, Sampath D, Fanini F, Vannini I, Musuraca G, Dell’Aquila M, Alder H, Davuluri RV, Rassenti LZ, Negrini M, Nakamura T, Amadori D, Kay NE, Rai KR, Keating MJ, Kipps TJ, Calin GA, Croce CM.
Author information
1
Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.
Figure 1B. http://imgur.com/zwXDrVI
Mol Cell Biol. 2000 Jul;20(14):5330-42.
A Pentamer Transcriptional Complex Including tal-1 and Retinoblastoma Protein Downmodulates c-kit Expression in Normal Erythroblasts
Luigi Vitelli1, Gianluigi Condorelli2,*, Valentina Lulli1, Trang Hoang3, Luisella Luchetti2, Carlo M. Croce2, and Cesare Peschle1,2,*
–
Author Affiliations
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-55412;
Department of Hematology-Oncology, Istituto Superiore di Sanità, 00161 Rome, Italy1; and
Clinical Research Institute, Montreal, Canada3
https://pubpeer.com/publications/63CD0FBC5DDD651B661C228A7DB8FF#2
Figure 3A. http://imgur.com/CPpRA97
Figure 3B. http://imgur.com/tLZgAyL
Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):5316-21. doi: 10.1073/pnas.1202465109. Epub 2012 Mar 19.
MicroRNAs/TP53 feedback circuitry in glioblastoma multiforme.
Suh SS1, Yoo JY, Nuovo GJ, Jeon YJ, Kim S, Lee TJ, Kim T, Bakàcs A, Alder H, Kaur B, Aqeilan RI, Pichiorri F, Croce CM.
Author information
1
Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.
https://pubpeer.com/publications/9EF1820BDACE55506D0C7BE135A542#undefined
Figure 5D. http://imgur.com/erOlIuv
2017 retraction.
J Biol Chem. 2008 May 16;283(20):13736-44. doi: 10.1074/jbc.M709062200. Epub 2008 Mar 3.
Fhit interaction with ferredoxin reductase triggers generation of reactive oxygen species and apoptosis of cancer cells.
Trapasso F1, Pichiorri F, Gaspari M, Palumbo T, Aqeilan RI, Gaudio E, Okumura H, Iuliano R, Di Leva G, Fabbri M, Birk DE, Raso C, Green-Church K, Spagnoli LG, Venuta S, Huebner K, Croce CM.
Author information
1
Ohio State University, Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
2017 retraction notice.
http://www.jbc.org/content/292/34/14279
This article has been withdrawn by the authors because of errors that occurred in the construction of Figs. 1D, 3C, 5C, and 5H, and supplemental Fig. 1A have been brought to their attention. The authors state that the errors do not affect the conclusions of the article, which have been confirmed in subsequent articles.
© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
http://radio.wosu.org/post/amid-ethics-concerns-ohio-state-stands-behind-researcher-carlo-croce#stream/0
Oncogene. 2006 May 11;25(20):2860-72.
Fhit modulation of the Akt-survivin pathway in lung cancer cells: Fhit-tyrosine 114 (Y114) is essential.
Semba S1, Trapasso F, Fabbri M, McCorkell KA, Volinia S, Druck T, Iliopoulos D, Pekarsky Y, Ishii H, Garrison PN, Barnes LD, Croce CM, Huebner K.
Author information
1
Comprehensive Cancer Center and Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, 43210, USA.
Figures 1b, 2b and 3b. http://imgur.com/GZFjL5O
Figure 1b. http://imgur.com/Ig4EYme
Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):12885-90. doi: 10.1073/pnas.0806202105. Epub 2008 Aug 26.
MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis.
Pichiorri F1, Suh SS, Ladetto M, Kuehl M, Palumbo T, Drandi D, Taccioli C, Zanesi N, Alder H, Hagan JP, Munker R, Volinia S, Boccadoro M, Garzon R, Palumbo A, Aqeilan RI, Croce CM.
Author information
1
Department of Molecular Virology, Ohio State University, Columbus, OH 43210, USA.
Figure 3A. http://imgur.com/FeMn8EK