ABCG2 Protein Levels and Association to Response to First-Line Irinotecan-Based Therapy for Patients with Metastatic Colorectal Cancer
Abstract
:1. Introduction
2. Results
2.1. Patients and Outcome
2.2. ABCG2
3. Discussion
4. Materials and Methods
4.1. Patients and Tumor Material
4.2. ABCG2 Immunohistochemistry
4.3. Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
5-FU | 5-fluorouracil |
Oxa | oxaliplatin |
Bev | bevacizumab |
HR | hazard ratio |
CI | confidence interval |
CRC mCRC TOP1 | Colorectal cancer Metastatic Colorectal Cancer Topoisomerase 1 enzyme |
ABC | ATP-binding cassette |
References
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Total N (%) | ABCG2 Low N (%) | ABCG2 High N (%) | Fisher’s Exact Test p | ||
---|---|---|---|---|---|
Patients included | 108 (100) | 72 (67) | 36 (33) | ||
Gender | Males | 61 (56) | 37 (61) | 24 (39) | 0.15 |
Females | 47 (44) | 35 (74) | 12 (26) | ||
Age | <65 | 70 (65) | 44 (63) | 26 (37) | 0.29 |
≥65 | 38 (35) | 28 (74) | 10 (26) | ||
WHO PS | 0 | 71 (66) | 46 (65) | 25 (35) | 0.67 |
1–2 | 37 (34) | 26 (70) | 11 (30) | ||
Location primary tumor | Right | 30 (28) | 19 (63) | 11 (37) | 0.84 |
Left | 40 (37) | 28 (70) | 12 (30) | ||
Rectum | 38 (35) | 25 (66) | 13 (34) | ||
Primary tumor resected | Yes | 98 (91) | 62 (63) | 36 (37) | 0.029 |
No | 10 (9) | 10 (100) | 0 (0) | ||
Prior radiotherapy | Yes | 9 (8) | 5 (56) | 4 (44) | 0.48 |
No | 99 (92) | 67 (68) | 32 (32) | ||
Adjuvant chemotherapy | No | 65 (60) | 42 (65) | 23 (35) | 0.43 |
5-FU | 14 (13) | 8 (57) | 6 (43) | ||
5-FU + Oxa | 29 (27) | 22 (76) | 7 (24) | ||
Number of metastatic sites | 1 | 33 (30) | 24 (73) | 9 (27) | 0.36 |
2 | 42 (39) | 29 (69) | 13 (31) | ||
>2 | 30 (28) | 17 (57) | 13 (43) | ||
Unknown | 3 (3) | ||||
Liver metastases | Yes | 31 (29) | 18 (58) | 13 (42) | 0.26 |
No | 77 (71) | 54 (70) | 23 (30) | ||
Lung metastases | Yes | 39 (36) | 25 (64) | 14 (36) | 0.68 |
No | 69 (64) | 47 (68) | 22 (32) |
Response | No-Response | Response vs. No-Response | |||||
---|---|---|---|---|---|---|---|
N (%) | N (%) | N (%) | OR | 95% CI | p | ||
Study population a | 101 (100) | 43 (43) | 58 (57) | ||||
ABCG2 | Low | 71 (70) | 34 (48) | 37 (52) | 2.14 | 0.86–5.32 | 0.10 |
High | 30 (30) | 9 (30) | 21 (70) | (ref) b |
Total N (%) | Progression-Free Survival | Overall Survival | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
108 (100) | HR | 95% CI | p | HR | 95% CI | p | ||||
Gender | Males | 61 (56) | 1.08 | 0.73–1.60 | 0.70 | 0.92 | 0.62–1.35 | 0.66 | ||
Females | 47 (44) | (ref) | (ref) | |||||||
Age | Per 10 year increase | 1.06 | 0.86–1.30 | 0.59 | 1.04 | 0.84–1.28 | 0.75 | |||
WHO PS | 0 | 71 (66) | 0.69 | 0.45–1.04 | 0.07 | 0.74 | 0.49–1.10 | 0.14 | ||
1–2 | 37 (34) | (ref) | (ref) | |||||||
Location primary tumor | Right | 30 (28) | 0.78 | 0.48–1.29 | 0.34 | 0.97 | 0.60–1.60 | 0.91 | ||
Left | 40 (37) | 1.18 | 0.75–1.85 | 0.47 | 1.19 | 0.76–1.87 | 0.46 | |||
Rectum | 38 (35) | (ref) | (ref) | |||||||
Primary tumor resected | Yes | 98 (91) | 0.8 | 0.41–1.53 | 0.49 | 0.79 | 0.41–1.52 | 0.48 | ||
No | 10 (9) | (ref) | (ref) | |||||||
Prior radiotherapy | Yes | 9 (8) | (ref) | (ref) | ||||||
No | 99 (92) | 0.52 | 0.26–1.04 | 0.07 | 0.6 | 0.30–1.21 | 0.15 | |||
Adjuvant chemotherapy | No | 65 (60) | (ref) | (ref) | ||||||
5-FU | 14 (13) | 1.5 | 0.82–2.75 | 0.19 | 1.2 | 0.67–2.15 | 0.54 | |||
5-FU + Oxa | 29 (27) | 2.62 | 1.63–4.22 | <0.001 | 2.16 | 1.37–3.39 | 0.001 | |||
Number of metastatic sites | 1 | 33 (30) | (ref) | (ref) | ||||||
2 | 42 (39) | 1.07 | 0.67–1.70 | 0.78 | 1.3 | 0.81–2.07 | 0.27 | |||
>2 | 30 (28) | 1.33 | 0.80–2.21 | 0.27 | 2.00 | 1.18–3.36 | 0.010 | |||
Unknown | 3 (3) | |||||||||
Liver metastases | Yes | 31 (29) | 1.00 | 0.66–1.53 | 0.99 | 1.23 | 0.80–1.87 | 0.34 | ||
No | 77 (71) | (ref) | (ref) | |||||||
Lung metastases | Yes | 39 (36) | 0.96 | 0.64–1.44 | 0.85 | 1.08 | 0.73–1.62 | 0.7 | ||
No | 69 (64) | (ref) | (ref) |
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Share and Cite
Palshof, J.A.; Cederbye, C.N.; Høgdall, E.V.S.; Poulsen, T.S.; Linnemann, D.; Nygaard, S.B.; Stenvang, J.; Christensen, I.J.; Jensen, B.V.; Pfeiffer, P.; et al. ABCG2 Protein Levels and Association to Response to First-Line Irinotecan-Based Therapy for Patients with Metastatic Colorectal Cancer. Int. J. Mol. Sci. 2020, 21, 5027. https://doi.org/10.3390/ijms21145027
Palshof JA, Cederbye CN, Høgdall EVS, Poulsen TS, Linnemann D, Nygaard SB, Stenvang J, Christensen IJ, Jensen BV, Pfeiffer P, et al. ABCG2 Protein Levels and Association to Response to First-Line Irinotecan-Based Therapy for Patients with Metastatic Colorectal Cancer. International Journal of Molecular Sciences. 2020; 21(14):5027. https://doi.org/10.3390/ijms21145027
Chicago/Turabian StylePalshof, Jesper Andreas, Camilla Natasha Cederbye, Estrid Vilma Solyom Høgdall, Tim Svenstrup Poulsen, Dorte Linnemann, Sune Boris Nygaard, Jan Stenvang, Ib Jarle Christensen, Benny Vittrup Jensen, Per Pfeiffer, and et al. 2020. "ABCG2 Protein Levels and Association to Response to First-Line Irinotecan-Based Therapy for Patients with Metastatic Colorectal Cancer" International Journal of Molecular Sciences 21, no. 14: 5027. https://doi.org/10.3390/ijms21145027