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. 2020 Sep;48(9):300060520954764.
doi: 10.1177/0300060520954764.

LMX1B-associated gankyrin expression predicts poor prognosis in glioma patients

Xu Guo  1 , Haozhe Piao  2 , Yixue Xue  3 , Yunhui Liu  1 , Hongyu Zhao  1
Affiliations

LMX1B-associated gankyrin expression predicts poor prognosis in glioma patients

Xu Guo et al. J Int Med Res. 2020 Sep.

Abstract

Objective: To explore the potential of the transcription factor LMX1B and downstream gankyrin as prognostic biomarkers of glioma.

Methods: The expression levels of gankyrin and LMX1B were detected in 52 normal brain specimens and 339 glioma specimens. Correlations of gankyrin and LMX1B expression levels with pathological stages and clinical characteristics were statistically analyzed. Furthermore, the binding of LMX1B to the gankyrin promoter was evaluated using ALGGEN PROMO.

Results: Levels of LMX1B and gankyrin were significantly increased in tumor tissue, and were significantly associated with advanced glioma grade and poor survival. Compared with gankyrin- and LMX1B-negative glioma, the mean survival of patients with higher gankyrin and LMX1B expression was significantly reduced, from 83.46 to 18.87 months and from 63.79 to 18.29 months, respectively. Furthermore, LMX1B had a moderate positive correlation with gankyrin expression (Pearson's r = 0.650), and it was also found to act as a transcription factor with NF-κB and E47 on the gankyrin promoter.

Conclusions: Increased expression of LMX1B and gankyrin has independent prognostic value in glioma patients. The transcription factor LMX1B may have an upstream role in the mechanism of action.

Keywords: LMX1B; gankyrin; glioblastoma multiforme; glioma; prognosis; transcription factor.

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Figures

Figure 1.
Figure 1.
Expression profiles of gankyrin in glioblastoma multiforme (GBM) patients by UALCAN dataset analysis. (a) Gankyrin expression was upregulated in 156 GBM tissue specimens compared with five normal brain tissue specimens. Gankyrin expression stratified by sex, race, and age are shown in the results of (b), (c), and (d), respectively.
Figure 2.
Figure 2.
Gankyrin and LMX1B expression levels were associated with advanced tumor stage of glioma. Representative images of immunohistochemical staining of gankyrin (a) and LMX1B (b) in normal brain tissue (NBT) and glioma tumor tissue with different World Health Organization grades. Upper panel: magnification ×200. Lower panel magnification ×400. (c) Histogram of gankyrin and LMX1B expression levels based on the immunoreactivity score (IRS) system from immunohistochemistry experiments. * indicates a significant difference compared with NBT, # indicates a significant difference compared with grade I tissue, ζ indicates a significant difference compared with grade II tissue, and ξ indicates a significant difference compared with grade III tissue. *, #, ζ, and ξ represent P < 0.05; **, ##, ζζ, and ξξ represent P < 0.01; and ***, ###, ζζζ, and ξξξ represent P < 0.001.
Figure 3.
Figure 3.
Gankyrin as the potential target of transcription factor LMX1B. (a) Bioinformatic analysis of 1700 bp upstream of the gankyrin promoter region, using PROMO/TRANSFAC. In addition to identifying five LMX1B (FLAT element) binding sites in the gankyrin promoter, there were also three NF-κB and seven E47 binding sites located in the vicinity of the LMX1B binding sites.
Figure 4.
Figure 4.
Higher gankyrin and LMX1B expression levels were associated with worse survival in patients with glioma. (a) Kaplan–Meier survival analysis of 339 glioma patients stratified for gankyrin expression. Higher gankyrin expression was significantly associated with worse survival. (b) Survival analysis stratified by LMX1B expression in 339 glioma patients. Higher LMX1B expression was significantly associated with worse survival.
Figure 5.
Figure 5.
Expression profiles of LDB1 in glioblastoma multiforme (GBM) patients by UALCAN dataset analysis. (a) LDB1 expression was upregulated in 156 GBM tissue specimens compared with five normal brain tissue specimens. LDB1 expression levels stratified by sex, race, and age are shown in the analysis results of (b), (c), and (d), respectively. Differences were statistically significant at *P < 0.05, **P < 0.01, and ***P < 0.001.
Figure 6.
Figure 6.
Expression profiles of RLIM in glioblastoma multiforme (GBM) patients by UALCAN dataset analysis. (a) RLIM expression was upregulated in 156 GBM tissue specimens compared with five normal brain tissue specimens. RLIM expression levels stratified by sex, race, and age are shown in the analysis results of (b), (c), and (d), respectively. Differences were statistically significant at *P < 0.05, **P < 0.01, and ***P < 0.001.
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