Fig 2: (A) Tuning parameter (?) selection in the LASSO algorithm performed using 1,000-fold cross-validation via the minimum criteria. The LASSO coefficient profiles of the 19 genes. A coefficient profile plot is produced versus the log (?). The binomial deviance is plotted versus log (?) and the black vertical lines are plotted at the optimal ? based on the minimum criteria. (B) The forest plots of multivariate Cox analysis results of 19 genes selected by LASSO algorithm. (C) The mRNA expression difference of AGPAT3, AKR1B1, PLD1, and UGT8 between alive and dead GC patients. (D) The KM survival curves of low-, moderate- and high-risk “AAPU” genes profile in TCGA cohort.

Fig 3: (A) Representative images of IHC for AGPAT3, AKR1B1, PLD1, and UGT8 in GC case with a H&E staining, ×10. (B) KM survival curves of low- and high-level AGPAT3, AKR1B1, PLD1, and UGT8 in Wuhan Union Hospital cohort. (C) The KM survival curves of low-, moderate- and high-risk “AAPU” genes profile in the WH cohort.

Fig 4: Schematic of PLD1 in gemcitabine resistance.

Fig 5: Potential roles for PLD1 as a marker for gemcitabine resistance therapy. (A) PLD1-high and -low expression groups of three PDAC organoids each were subcutaneously inoculated in nude mice on day 0. Tumor volume was measured every 3 d using calipers. Gemcitabine or Vu0155069 was injected intraperitoneally three times per week (red plots represent time points of drug administration). (B) Tumor growth curves of the four groups. (C) Statistical analysis of tumor growth inhibition rates from different groups. (D) Tumor weights at the end of the experiment. (E) Three representative bioluminescent images of the four groups on d 7 and 21 after tumor implantation. (F) C57BL/6 mice were orthotopically injected with 1 × 106 luciferase-expressing KPC cells or luciferase-expressing cells in Matrigel. Gemcitabine or Vu0155069 was injected intraperitoneally three times per week (red plots represent time points of drug administration). (G) Statistical analysis of the BLI fold-change after treatment (BLI on d 21 to BLI on d 7). ***P < 0.001 by non-paired Student’s t-test (n = 9 per group). (H) C57BL/6 mice were orthotopically injected with 1 × 106 luciferase-expressing KPC cells or luciferase-expressing cells in Matrigel. Gemcitabine or Vu0155069 was injected intraperitoneally three times per week until death (red plots represent time points of drug administration). (I) Kaplan–Meier survival curves with log-rank test for significance between gemcitabine treatment and gemcitabine plus Vu0155069 treatment. All mouse experiments were independently repeated three times using nine mice per experimental group in the orthotopic tumor model. Representative data are shown. Data are presented as the mean ± SD. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; ns, not significant.