Overexpression of YAP and TAZ is an independent predictor of prognosis in colorectal cancer and related to the proliferation and metastasis of colon cancer cells
Authors: Xiang Zhang
Zhangyan Guo
Weihong Wen
Lijuan Wang
Qing Zhu
Shengjia Shi
Angang Yang
Suxia Han
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: YAP; TAZ; colorectal cancer; prognosis; survival
Affiliations: Department of Oncology, The First Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, P. R. China.

Abstract:  Background and objective: Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are nuclear effectors of the Hippo pathway. Although they are abundantly expressed in the cytoplasm and nuclei of human colorectal cancer (CRC), and related to tumor proliferation status, there have been few studies on the predictive role of YAP and TAZ expression on the overall survival of patients with CRC. This study investigated YAP and TAZ expression in both CRC patients and colon cancer cell lines, and assessed their prognostic value. Methods: Paraffin-embedded specimens from 168 eligible patients were used to investigate YAP and TAZ expression by immunohistochemistry, and compared with experimental results in colon cancer HCT116 cell line to explore their clinical significance in CRC. Results: Statistically significant positive correlations were found between protein expression of YAP and TAZ in CRC tissues. Patients with higher YAP or TAZ expression showed a trend of shorter survival times; more importantly, our cohort study indicated that patients with both YAP and TAZ overexpression presented the worst outcomes. This was supported by multivariate analysis. In HCT116 colon cancer cells, the capacity for proliferation, metastasis, and invasion was dramatically reduced by knockdown of YAP and TAZ expressions by siRNA. Conclusions: Co-overexpression of YAP and TAZ is an independent predictor of prognosis for patients with CRC, and may account for the higher proliferation, metastasis, and poor survival outcome of these patients. 

Retracted: No

PubPeer comments:
 Concern about Figure 5. Several panels in A and C appear to show areas of overlap. ![file] This was reported to the journal in October 2015. , 
 #1 Dear Dr. Elisabeth M Bik: Iu2019m Wang Lijuan, the first author of the mentioned manuscript. Thank you for bringing our attention to this figure. We apologize for this inadvertent error that had occurred during figure layout. After you point it out, one of the corresponding author professor Zhu Qing immediately carry out a thorough examination of the concerning authors and original data. But because many authors have graduated or left the research group many years ago, it took some time to get in touch all the authors. And she just gets in touch with me recently, which results in the late response. We regret that the images (Figure 5A and Figure 5C) were misincorporated during figure assembly when we were preparing for manuscript submission. We also regret that we didn t catch this error during subsequent revisions and examinations when the manuscript underwent the review and publication processes. After the initial investigation, we found the possible reason account for this careless mistake is the results of each groups were wrongly named. One co-author labeled the pictures of parental groups as 1 to 5, and si-NC group as 2-1 to 2-5, and so on when he took the pictures of transwell chamber of different groups with a microscope. But I carelessly misused the pictures which labeled 1 to 5 as the representative picture of parental group, si-NC group, si-YAP, si-TAZ, si-YAP+si-TAZ when I incorporated the separated pictures into the Figure 5. During these days, we tried to find and reanalysis the original data to replace the incorrected figure and confirm our conclusion. But due to we performed these experiment ten years ago during 2011 to 2012, the computer which stores these data was damaged. Thus, we failed to find the raw data. Now, we will immediately repeat these experiments and invite two third-party laboratory to repeat these experiments using the same methods as we described in the article. After our group and the third-party laboratory completed these experiments, we will prepare a correction request which we ll submit to the journal shortly. We apologize to our readers for any confusion this unintentional error might have caused. Thank you for your attention. Best regards Wang Lijuan , 
 Dear Dr. Elisabeth M Bik: Iu2019m Qing Zhu, one of the corresponding author of the manuscript u201cOverexpression of YAP and TAZ Is an Independent Predictor of Prognosis in Colorectal Cancer and Related to the Proliferation and Metastasis of Colon Cancer Cellsu201d which previously published in Plos One (PLoS One, 2013 Jun 10;8(6): e65539). I have received Email from the Pubpeer websites for the misincorporated figures in the previous published article before some months. Due to errors in figure preparation, the image of Figure 5A and Figure 5C are incorrect. We immediately carry out a thorough examination of the concerning data, and found the possible reason account for this careless mistake is the results of each groups were wrongly named. We labeled the pictures of parental groups as 1 to 5, and si-NC group as 2-1 to 2-5, and so on. But we misused the pictures which labeled 1 to 5 as the representative picture of parental group, si-NC group, si-YAP, si-TAZ, si-YAP+si-TAZ when we incorporated the separated pictures into the Figure 5. As the computer which stores raw data was damaged, we failed to find the raw data in the beginning. We tried our best to repair the computer and find the raw data during these days. Finally, we fixed the computer and found the raw data, and we further confirmed the reason account for this mistake was just as we had mentioned ahead. Furthermore, based on a rigorous scientific attitude, we will also immediately repeat these experiments and invite two third-party laboratory to repeat these experiments using the same methods as we described in the article. Next we will connect Plos One to make corrected Figure 5 to the previously published article. We apologize for this inadvertent error that had occurred during figure layout. We regret that the images were misincorporated during figure assembly when we were preparing for manuscript submission. We also regret that we didn t catch this error during subsequent revisions and examinations when the manuscript underwent the review and publication processes. We apologize to our readers for any confusion this unintentional error might have caused. Thank you for your generous help. Yours Sincerely, Dr. Qing Zhu , 
 #2 and #3 I appreciate the authors replying here and hope the exposure of these issues causes no personal harm. Unfortunately, in my opinion, there is no credible explanation that can address the image concerns illustrated by Dr. Bik in #1, other than an admission of fault. Because of this, I suggest the authors approach the journal to see if an u201cauthoru2019s retractionu201d is an option. Good luck. ,