CD38 Predicts Favorable Prognosis by Enhancing Immune Infiltration and Antitumor Immunity in the Epithelial Ovarian Cancer Microenvironment
Authors: Yang Liu
Zhou Jiang
Ying Zhu
Zhigang Zhang
Jianwei Zhou
Journal: Frontiers in Genetics (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CD38; antitumor immunity; ovarian cancer; prognosis; tumor-infiltrating lymphocytes.
Affiliations: Department of Gynecology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China., Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou, China.

Abstract:  The identification of predictive biomarkers and novel targets to optimize immunotherapy strategies for epithelial ovarian cancer (EOC) is urgently needed. CD38 is a multifunctional glycoprotein that acts as an ectoenzyme and immune receptor. However, the underlying immunological mechanisms and prognostic value of CD38 in EOC remain unclear. CD38 gene expression in EOC was evaluated by using Gene Expression Profiling Interactive Analysis (GEPIA) and TISIDB database. The prognostic value was calculated using GEPIA and Kaplan-Meier plotter. Gene set enrichment analysis was conducted to study the roles of CD38 in the EOC microenvironment. Furthermore, the relationship between CD38 expression level and immune cell infiltration was analyzed by the Tumor Immune Estimation Resource and TISIDB. The GEPIA and TISIDB databases showed that CD38 expression in EOC was higher than that in normal tissue and was highest in the immunoreactive subtype among the four molecular types. A total of 424 cases from GEPIA revealed that high levels of CD38 were associated with longer disease-free survival [hazard ratio (HR) = 0.66, P = 0.00089] and increased overall survival rate (HR = 0.67, P = 0.0016). Kaplan-Meier plotter also confirmed the prognostic value of CD38 in EOC. Data from The Cancer Genome Atlas database demonstrated that gene signatures in many categories, such as immune response and adaptive immune response, were enriched in EOC samples with high CD38 expression. In addition, CD38 was positively correlated with immune cell infiltration, especially infiltration of activated CD8+ T cells, CD4+ T cells, and B cells. CD38 is positively correlated with prognosis and immune cell infiltration in the EOC microenvironment and contributes to the regulation of antitumor immunity. CD38 could be used as a prognostic biomarker and potential immunotherapy target. 

Retracted: No

PubPeer comments:
 The scratch assays in this paper are problematic throughout. The cleared space (in every single assay!) is, on closer inspection, clearly an inserted uniform gray box and not a microscope image. Moreover, the imaged cells feature numerous duplications and edits. I have only added an example below. Note the copied (but flipped) image of cells (red), and the cloned elements used to fill out the space (orange lime). ![file] In addition, the images of the tumors is clearly a composite of multiple images. Note the incompatible shadows (purple) and the clearly edited truncated shadow (blue). ![file] , 
 In Figure 2D and 5C, areas of several flow cytometry dot plots are duplicated and presented as something else in another dot plot. ![file] ![file] , 
 Retracted [20 November 2020] . ----------------------------------------------------------- The Editor and Publisher of OncoTargets and Therapy wish to retract the published paper. The journal was notified of possible image manipulation and duplication in: - Figure 2D - panels MGC803 Blank, si-NC, siHCG18 and panels AGS Blank, si-NC, si-HCG18, which all appeared to share duplicated elements - Figure 3A - panels AGS 0 h si-NC and 48 h Blank, which appeared to show duplicated elements shared between both images - Figure 5C - panels PI si-NC, si-HCG18 and siHCG18+740-P - Figure 6A - panels Mock 4 w, si-HCG18 2 w and siHCG18 4 w, which appeared to show image splicing and irregular shadowing The authors were unable to provide the necessary raw data for their study and the editor determined the findings of the study were no longer valid. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. ,