THEM6-mediated reprogramming of lipid metabolism supports treatment resistance in prostate cancer (2021)
Figure 6

Figure 6: THEM6 is a clinically relevant target in CRPC.

A, Gene expression analysis of THEM6/c8orf55 in normal and tumoural prostate tissues according to the PRAD TCGA dataset (n=489).

B, Gene expression analysis of THEM6/c8orf55 in benign, localised and metastatic tumoural prostate tissues according to the GSE35988 dataset (n=122).

C, Kaplan-Meier progression-free survival analysis of PCa patients stratified according high and low THEM6 expression using the PRAD TCGA dataset.

D, Kaplan-Meier recurrence-free survival analysis of PCa patients stratified according to median THEM6 expression using the GSE21034 dataset (n = 179).

E, IHC staining of THEM6 expression in treatment naïve, NHT-treated, CRPC and NEPC tumours. Scale bar represents 100 µm.

F, Quantification of THEM6 staining in PCa tissue samples.

G-H, Quantification of THEM6 expression in PCa tissue samples according to Gleason score (G) and metastatic status (H) in the patients analysed in F.

I-J, Kaplan-Meier recurrence-free (I) and overall (J) survival analysis of PCa patients stratified according to median THEM6 expression.

K, Quantification of THEM6 expression in PCa tissue samples according to Ki67 expression in the patients analysed in F.

L, Quantification of THEM6 expression in PCa tissue samples according to Ki67 expression in the patients analysed in I-J.

M, Volcano plot of the differentially modulated genes in PCa patients from the PRAD TCGA stratified according to THEM6 expression. Red dots represent the UPR-related genes extracted from the UPR-gene signature obtained from (Adamson et al., 2016).

N, Gene set enrichment plot analysed from PCa patients of the PRAD TCGA dataset using the UPR gene signature obtained from (Adamson et al., 2016).

Data information: Panels A, B: Center line corresponds to median of data, top and bottom of box correspond to 75th and 25th percentile, respectively. Whiskers extend to adjacent values (minimum and maximum data points not considered outliers). Panel F: Centre line corresponds to median of data, top and bottom lines correspond to upper and lower quartiles. Panels G, H, K, L: Centre line corresponds to median of data, top and bottom of box correspond to 90th and 10th percentile, respectively. Whiskers extend to adjacent values (minimum and maximum data points not considered outliers). Statistical analysis: A, B: pairwise ANOVA. C, D, I, J: logrank test. F: 1-way ANOVA with a Dunnett's multiple comparisons test. G, H, K, L: two-tailed Mann-Whitney U test. Data reproducibility: Panels A, C: n = 489 tumours. Panel B: n = 122 tumours. Panel D: n = 179. Panels E, F: n = 132; 90; 66; 137; 44; 30 tumours for Untreated; NHT 1-3; NHT4-6; NHT>7; CRPC; NEPC respectively. Panel G: n = 99 tumours for Gleason score ≤ 7 and n = 63 tumours for Gleason score > 7. Panel H: n = 151 tumours for non-metastatic patients and n = 76 tumours for metastatic patients. Panels I, J: n = 35 tumours for THEM6 low and n = 34 tumours for THEM6 high. Panel K: n = 269 tumours for Ki67 low and n = 270 tumours for Ki67 high. L: n = 35 tumours for Ki67 low and n = 29 tumours for Ki67 high. Panel M: n = 489 tumours.

SUPPLEMENTARY FIGURE LEGENDS