LPAR5 stimulates the malignant progression of non-small-cell lung carcinoma by upregulating MLLT11
Authors: Q-K Chen
J-F Xu
H-P Zhang
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: LPAR5; NSCLC; diagnostic marker; prognostic value; metastasis
Affiliations: Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. .

Abstract:  Objective: This study aims to explore the diagnostic and prognostic values of Lysophosphatidic acid receptor 5 (LPAR5) in non-small-cell lung cancer (NSCLC) and its regulatory effects on biological functions of NSCLC cells. Patients and methods: NSCLC and adjacent non-tumoral tissues were collected for analyzing differential levels of LPAR5 by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Clinical information of recruited NSCLC patients was collected for assessing the diagnostic and prognostic values of LPAR5. In vitro regulation of LPAR5 on proliferative and migratory potentials of H1299 and SPC-A1 cells was examined by Cell Counting Kit-8 (CCK-8) and transwell assay, respectively. In addition, in vivo regulation of LPAR5 on the growth rate of NSCLC in nude mice was detected by tumorigenicity assay. The interaction between LPAR5 and its downstream target MLLT11 was determined by rescue experiments. Results: LPAR5 was upregulated in NSCLC tissues than adjacent non-tumoral ones. High level of LPAR5 predicted higher rates of lymphatic metastasis and distant metastasis, as well as worse overall survival and progression-free survival in NSCLC. Knockdown of LPAR5 not only attenuated in vitro proliferative and migratory abilities in H1299 and SPC-A1 cells, but also slowed down in vivo growth of NSCLC in nude mice. MLLT11 was upregulated in NSCLC tissues, and displayed a positive correlation to LPAR5. Overexpression of MLLT11 was able to reverse the attenuated in vitro proliferative and migratory abilities, and the suppressed in vivo growth of NSCLC because of LPAR5 knockdown. Conclusions: LPAR5 stimulates proliferative and migratory potentials in NSCLC by positively regulating MLLT11, which can be served as an effective diagnostic marker for early stage NSCLC. 

Retracted: No

PubPeer comments:
 This paper appears to be part of a large set of papers (n=190 as of today and growing) that share a very similar layout. Subsets of these papers appear to share similar Kaplan-Meier survival plots, correlation plots, flow cytometry panels, and overlapping photos of wound-healing, transwell assays, etc. Yet, there is little to no overlap between the authors of these papers or their departments and affiliated institutions. I have been calling this set the  Comb papers, because the Kaplan-Meier plots have a comb-like appearance. For PubPeer user Hoya Camphorifolia, the survival plots look like Lego blocks. Many of these survival plots show a sudden drop of survival at 75 months. Another characteristic is the lack of percentages in their Tables I, in columns labeled with percentages, and the nicely even spread of patients into roughly equally-sized group, no matter which parameter is chosen. The very similar layout and overlapping photos suggest these papers might have all been created by the same entity, perhaps a paper mill. Here is Figure 1D from this paper, showing the Comb- (or Lego-)like survival plots with their nosedive at 75 months. ![file] And here is Table I with its undelivered percentages in the High Low columns. ![file] , 
 Figure 2C. * Red boxes: Two panels appear to show an overlap. ![file] , 
  Here is Figure 1D from this paper  Overall survival and progression-free survival in NSCLC patients classified by LPAR5 level. ![] The proportions of patients surviving **without** progression are somehow greater than for the larger group of patients surviving **with or without** progression. Am I missing something? ,