Circular RNA profiling and its potential for esophageal squamous cell cancer diagnosis and prognosis
Authors: Qiang Cao
Liyuan Fan
Junpeng Zhang
Baosheng Li
Jia Liu
Journal: Molecular Cancer (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Biomarkers; Circular RNAs; Esophageal squamous cell cancer; Exosome; hsa_circ_0001946.
Affiliations: Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Jinan, 250117, China., School of Computer Science and Engineering, Southeast University, Nanjing, China., Department of Clinical Laboratory, the Second Hospital of Shandong University, Jinan, China., Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Jinan, 250117, China. .

Abstract:  Esophageal squamous cell cancer (ESCC) is a high incidence and mortality disease worldwide. However, specificity and sensitivity of its diagnostic and prognostic biomarkers are still unsatisfactory. Recently, circular RNAs (circRNAs) as biomarkers have been studied extensively while the expression profile and clinical significance of circRNAs in ESCC have rarely been studied. We performed circular RNA microarray in 3 pairs of ESCC frozen tumor and non-tumor tissues to identify ESCC-related circRNAs and found 1045 up-regulated and 1032 down-regulated circRNAs among which 6 circRNAs (hsa_circ_0062459, hsa_circ_0076535, hsa_circ_0072215, hsa_circ_0042261, hsa_circ_0001946, and hsa_circ_0043603) displayed consistency with microarray results by qRT-PCR. 3 circRNAs (hsa_circ_0062459, hsa_circ_0001946, and hsa_circ_0043603) were also detected in plasma and 2 of them except hsa_circ_0062459 could be used as diagnostic biomarkers and found in exosome of cell-conditioned culture conditioned media. The AUC, sensitivity and specificity of hsa_circ_0001946 were 0.894, 92, 80%, of hsa_circ_0043603 were 0.836, 64, 92% while a signature combining them were 0.928, 84 and 98%. Hsa_circ_0001946 was confirmed to predict the recurrence, overall survival (OS) and disease-free survival (DFS) in frozen and FFPE tissues, while its overexpression decreased cell proliferation, migration, and invasion. 

Retracted: No

PubPeer comments:
 Supplemental Figure 7E. * Blue boxes: The 24h K50-N panel appears to show an overlap with the 24h K50-V panel. ![file] , 
 Supplemental Figure 7I. * Yellow boxes. In the TE-1-V row, the  migration and  invasion panels appear to show an area of overlap. ![file] , 
 Two corrections were issued for this paper. * Correction 1, 05 August 2019, found here: https: molecular-cancer.biomedcentral.com articles 10.1186 s12943-019-1050-y - this corrects a funding statement error:  The funding number provided was 2016YFC0105100 and should be corrected to 2016YFC0105106. We apologize for this error, which does not affect any of the interpretations or conclusions of the article. * Correction 2, 02 July 2020, found here: https: molecular-cancer.biomedcentral.com articles 10.1186 s12943-020-01230-5 The second correction reads:  Following the publication of [1], we recently found some errors in the manuscripts and figures. In text section u201cHsa_circ_0001946 as a prognostic biomarker in both frozen and FFPE tissuesu201d of Page 3, we wrote u201clongeru201d as u201cshorteru201d in the manuscripts. The corrected context is presented as below. Hsa_circ_0001946 as a prognostic biomarker in both frozen and FFPE tissues As Additional file 6: Table S2 showed, hsa_circ_0001946 was the only one associated with the recurrence rate of ESCC patients. As for disease-free survival (DFS) and overall survival (OS) prediction, patients in the high hsa_circ_0001946 group (according to the median level) had a much longer DFS and OS (Fig. 2a and Fig. 2e), whose hazard ratio (HR) and 95% confidence interval (CI) were 0.357(0.164u20130.781) and 0.209(0.076u20130.579) respectively. Furthermore, we used FFPE tissues to verify this conclusion. The results showed that high hsa_circ_0001946 was associated with longer DFS and OS in K-M curves (Fig. 2b and Fig. 2f) while univariate Cox proportional hazard models showed that expression of hsa_circ_0001946 in FFPE tissues was an independent prognostic indicator of OS but not DFS. The multivariate Cox proportional hazard models shown that combination of these two group supports the result that hsa_circ_0001946 was a promising and independent prognostic biomarker for ESCC patients in both frozen and FFPE tissues. In Figure 3E, the legend of tumor growth curve (left panel) was reversedly marked between Eca109-V and Eca109-N group. The modified plot with corrected legend were presented below. In Figure S7, the image of TE-1-V in migration assay (Figure S7I) and the image of wound-healing assay of K50-N (24h, median column Figure S7E) were arranged in wrong placed. These image errors were caused by repeatedly selecting, below is the corrected images. These errors were caused by our carelessness and misoperation in image combination. After carefully re-checked the manuscripts, raw data, and lab records. We assure that the correction of these will not alter the conclusion of the results. We sincerely apologize for the errors and any confusion it may have caused. ,