Table 2. Markers of cell death in normal and pancreatic cancer tissue and following neoadjuvant therapy.
Markers | Normal Pancreas (n = 13) | 1 P value Normal vs Control | No neoadjuvant therapy (control) (n = 13) | Control vs Gemcitabine vs FOLFIRINOX 2P | Gemcitabine- based neoadjuvant therapy (n = 14) | Gemcitabine vs FOLFIRINOX 1P | FOLFIRINOX neoadjuvant therapy (n = 11) |
---|---|---|---|---|---|---|---|
Median (95% CI) | Median (95% CI) | Median (95% CI) | Median (95% CI) | ||||
CK7+ cells / per mm2 | 147.0 (8.00–244.0) | 0.0006 | 518.5 (197.0–673.0) | 0.0158 | 195.0 (53.00–298.0) | NS | 393.0 (99.00–773.0) |
Collagen mm2 / Area mm2 (%) | 7.7 (6.87–14.9) | <0.0001 | 25.9 | 0.0117 | 32.8 | NS | 36.52 |
16.49-32.96 | 27.59–41.56 | 8.4–51.2 | |||||
αSMA+ cells/ total cells % | 2.9 | <0.0001 | 31.3 | 0.0067 | 33.4 | 0.0128 | 61.8 |
1.62–6.82 | 20.95–52.39 | 40.73–75.27 | |||||
Ratio αSMA/ Collagen | 0.400 (0.210–0.850) | 0.0015 | 1.485 (0.600–3.500) | NS | 1.070 (0.730–1.500) | 0.0361 | 1.610 (1.040–2.120) |
Autophagy Markers | |||||||
p62/SQSTM1 in CK7+ cells % | 34.10 (4.70–93.90) | NS | 53.50 (6.600–77.60) | 0.0004 | 86.05 (62.50–97.10) | NS | 94.60 (93.40–98.00) |
BECLIN1+ cells/ total cells % | 33.18 (19.16–52.14) | 0.0056 | 4.032 (0.28–17.67) | NS | 2.91 (0.34–9.98) | NS | 5.59 (3.15–15.25) |
ATG5 in CK7+ cells % | 85.79 (72.72–90.85) | 84.04 (55.42–90.11) | NS | 88.34 (75.11–96.05) | NS | 69.41 (51.40–84.05) | |
ATG7 in CK7+ cells % | 56 (36.72–76.20) | NS | 80 (68.83–93.16) | NS | 66 (45.25–86.81) | NS | 61 (38.31–84.73) |
LC3 and LAMP2+ cells % | 43.82 (14.46–62.21) | 0.0140 | 12.94 (1.882–41.47) | NS | 16.03 (0.820–19.73) | NS | 12.60 (4.793–17.78) |
Necroptosis Markers | |||||||
RIP1 in CK7+ cells % | 11.07 (4.240–22.39) | 0.0048 | 71.49 (15.91–78.86) | NS | 69.31 (44.88–87.36) | NS | 80.20 (44.85–98.85) |
RIP3 in CK7+ cells % | 7.080 (3.400–64.17) | NS | 39.48 (6.070–56.72) | 0.0002 | 70.87 (36.57–90.09) | 0.0243 | 94.87 (77.00–98.92) |
pMLKL in CK7+ cells % | 3.900 (0.080–14.30) | NS | 0.4000 (0.150–4.180) | < 0.0001 | 4.495 (2.70–16.15) | 0.0022 | 19.08 (8.60–39.49) |
Apoptosis Markers | |||||||
BAX in CK7+ cells % | 14.62 (0.610–40.22) | NS | 14.53 (3.000–45.15) | 0.0004 | 44.16 (27.24–73.04) | 0.0299 | 75.27 (45.05–93.73) |
Cleaved Caspase-9 in CK7+ cells % | 40.46 (2.810–61.67) | NS | 30.06(6.98–48.42) | 0.0008 | 61.09 (41.98–78.55) | 0.0148 | 83.76 (72.77–90.86) |
Caspase-3 in CK7+ cells % | 6.100 (0.920–20.01) | NS | 4.145 (0.540–21.29) | 0.0007 | 27.97 (11.97–55.40) | NS | 52.87 |
(30.50–66.59) | |||||||
Inflammatory cell infiltrate Markers | |||||||
Extracellular HMGB1 per area % | 0.720 (0.0671–1.506) | NS | 1.361 (0.00–2.989) | 0.0102 | 3.027 (1.004–19.36) | NS | 3.424 (1.558–23.14) |
Macro-Φ cells % | 0.205 (0.110–0.590) | 0.0052 | 0.870 (0.410–5.270) | NS | 1.430 (0.910–2.060) | NS | 1.340 (0.530–5.270) |
CD8+ cells % | 0.39 (0.25–0.74) | NS | 0.95 (0.43–1.47) | 0.0016 | 2.05 (1.11–4.65) | NS | 4.06 (2.61–6.48) |
MPO Expression % | 0.175 (0.090–0.920) | 0.0205 | 0.665 (0.230–1.94) | NS | 0.65 (0.37–2.810) | NS | 2.00 (0.680–4.540) |
NF-κB p65 in CK7+ cells % | 19.01 (1.85–38.06) | NS | 33.37 (7.93–61.66) | 0.0008 | 80.20 (70.24–92.29) | NS | 83.81 (53.91–89.33) |
12 tailed Mann-Whitney U test; 2Kruskal-Wallis test.