Clinical Significance of Various Drug-Sensitivity Markers in Patients with Surgically Resected Pulmonary Pleomorphic Carcinoma
Abstract
:1. Introduction
2. Results
2.1. Patient Characteristics and Immunohistochemistry
2.2. Survival Analysis
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. Immunohistochemical Staining
4.3. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Markers | VEGFR2 | TUBB3 | STMN1 | Topo-II | TS | GRP78/BiP |
---|---|---|---|---|---|---|
Average score | 2.86 | 3.44 | 2.14 | 1.42 | 3.13 | 3.36 |
High-expression percentages | 33% (39/105) | 61% (64/105) | 35% (37/105) | 31% (33/105) | 51% (53/105) | 51% (53/105) |
Variables | Total (n = 105) | VEGFR2 | TUBB3 | STMN1 | Topo-II | TS | GRP78/BiP | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
High (n = 39) | Low (n = 66) | p | High (n = 64) | Low (n = 41) | p | High (n = 37) | Low (n = 68) | p | High (n = 33) | Low (n = 72) | p | High (n = 53) | Low (n = 52) | p | High (n = 53) | Low (n = 52) | p | ||
Age | |||||||||||||||||||
<69/≥69 (y) | 54/51 | 25/14 | 29/37 | 0.06 | 34/30 | 20/21 | 0.69 | 21/16 | 33/35 | 0.54 | 23/10 | 31/41 | 0.01* | 30/23 | 24/28 | 0.33 | 29/34 | 25/27 | 0.85 |
Gender | |||||||||||||||||||
Male/Female | 79/26 | 28/11 | 51/15 | 0.64 | 44/35 | 35/6 | <0.01* | 26/11 | 53/15 | 0.47 | 26/7 | 53/19 | 0.63 | 38/15 | 41/11 | 0.49 | 43/10 | 36/17 | 0.12 |
T factor | |||||||||||||||||||
T1-2/T3-4 | 65/40 | 25/14 | 40/26 | 0.83 | 37/28 | 28/13 | 0.31 | 21/16 | 44/24 | 0.52 | 12/21 | 53/19 | <0.01* | 29/24 | 36/16 | 0.16 | 39/14 | 26/16 | 0.29 |
N factor | |||||||||||||||||||
Absent/Present | 72/33 | 27/12 | 45/21 | >0.99 | 46/24 | 26/15 | 0.84 | 25/12 | 47/21 | >0.99 | 21/12 | 51/21 | 0.50 | 35/18 | 37/15 | 0.67 | 40/13 | 32/1 | 0.01* |
Pathological stage | |||||||||||||||||||
I-II/III-IV | 69/36 | 24/15 | 45/21 | >0.99 | 41/28 | 28/13 | 0.42 | 20/17 | 49/19 | 0.08 | 25/8 | 44/28 | 0.18 | 34/19 | 35/17 | 0.83 | 41/12 | 28/24 | 0.01* |
Smoking | |||||||||||||||||||
Yes/No | 84/21 | 28/11 | 56/10 | 0.13 | 51/13 | 33/8 | >0.99 | 27/10 | 57/11 | 0.21 | 27/5 | 57/15 | 0.75 | 44/9 | 40/12 | 0.47 | 46/7 | 38/14 | 0.09 |
Lymphatic permeation | |||||||||||||||||||
Absent/Present | 41/64 | 12/27 | 29/37 | 0.21 | 25/16 | 16/25 | 0.07 | 13/24 | 28/40 | 0.67 | 14/19 | 27/45 | 0.67 | 20/33 | 21/31 | 0.84 | 19/34 | 22/30 | 0.55 |
Vascular invasion | |||||||||||||||||||
Absent/Present | 31/74 | 11/28 | 20/46 | >0.99 | 20/11 | 11/30 | <0.01* | 10/27 | 21/47 | 0.82 | 10/23 | 21/51 | >0.99 | 16/37 | 15/37 | >0.99 | 15/38 | 16/36 | 0.83 |
Pleural invasion | |||||||||||||||||||
Absent/Present | 49/56 | 17/22 | 32/34 | 0.68 | 30/19 | 19/22 | 0.20 | 18/19 | 31/37 | 0.84 | 17/16 | 35/40 | 0.68 | 27/26 | 22/30 | 0.43 | 22/31 | 27/25 | 0.33 |
Adjuvant chemotherapy | |||||||||||||||||||
Absent /Present | 77/28 | 27/12 | 50/16 | 0.49 | 43/34 | 34/7 | 0.68 | 26/11 | 51/17 | 0.64 | 25/8 | 52/20 | 0.81 | 35/18 | 42/10 | 0.12 | 39/14 | 38/14 | >0.99 |
VEGFR2 | |||||||||||||||||||
High/Low | — | — | — | — | 25/39 | 14/27 | 0.52 | 19/18 | 20/48 | 0.03* | 14/19 | 25/47 | 0.51 | 24/29 | 15/37 | 0.11 | 21/32 | 18/34 | 0.68 |
TUBB3 | |||||||||||||||||||
High/Low | 64/41 | 25/14 | 39/27 | 0.52 | — | — | — | 17/10 | 37/31 | 0.49 | 18/15 | 46/26 | 0.39 | 41/12 | 23/29 | <0.01* | 36/17 | 28/24 | 0.16 |
Stathmin 1 | |||||||||||||||||||
High/Low | 37/68 | 19/20 | 18/48 | 0.03* | 27/37 | 10/31 | 0.49 | — | — | — | 12/21 | 25/47 | >0.99 | 31/22 | 6/46 | <0.01* | 21/32 | 16/36 | 0.41 |
Topo 2 | |||||||||||||||||||
High/Low | 33/72 | 14/25 | 19/47 | 0.51 | 18/46 | 15/26 | 0.39 | 12/25 | 21/47 | >0.99 | — | — | — | 18/35 | 15/37 | 0.67 | 19/34 | 14/38 | 0.40 |
TS | |||||||||||||||||||
High/Low | 53/52 | 24/29 | 15/37 | 0.11 | 41/12 | 23/29 | <0.01* | 31/22 | 6/46 | <0.01* | 18/35 | 15/37 | 0.67 | - | - | - | 30/23 | 23/29 | 0.24 |
GRP78/BiP | |||||||||||||||||||
High/Low | 53/52 | 21/32 | 18/34 | 0.68 | 36/17 | 28/24 | 0.16 | 36/17 | 28/24 | 0.16 | 21/32 | 16/36 | 0.41 | 30/13 | 23/29 | 0.01* | - | - | - |
OS | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Variables | All Patients | Patients with AC Component | Patients with Non-AC Component | |||||||||
MST | HR | 95% CI | p Value | MST | HR | 95% CI | p Value | MST | HR | 95% CI | p Value | |
Age, ≤69/>69 (y) | 361/1047 | 0.82 | 0.49–1.37 | 0.52 | 157/1038 | 1.34 | 0.59–3.04 | 0.48 | 352/1068 | 1.10 | 0.56–2.16 | 0.77 |
Gender (female/male) | 1038/654 | 0.83 | 0.46–1.51 | 0.55 | 1038/1009 | 1.06 | 0.44–2.54 | 0.89 | 881/147 | 0.63 | 0.27–1.49 | 0.30 |
p-stage (I-II/III-IV) | 1338/228 | 0.21 | 0.11–0.93 | <0.01 | 1839/615 | 0.33 | 0.13–0.83 | 0.01 | 1265/145 | 0.07 | 0.02–0.18 | <0.01 |
Ly (present/absent) | 624/1209 | 1.47 | 0.85–2.39 | 0.17 | 1009/1939 | 1.22 | 0.52–2.83 | 0.64 | 288/1047 | 1.56 | 0.78–3.11 | 0.20 |
v (present/absent) | 640/1265 | 1.41 | 0.82–2.41 | 0.21 | 1038/1839 | 1.16 | 0.49–2.72 | 0.72 | 353/1265 | 1.51 | 0.73–3.10 | 0.26 |
Pl (present/absent) | 615/1202 | 1.56 | 0.93–2.61 | 0.09 | 654/3665 | 1.95 | 0.86–4.41 | 0.11 | 336/1068 | 1.30 | 0.66–2.56 | 0.57 |
VEGFR2 (high/low) | 352/1209 | 2.23 | 1.28–3.83 | <0.01 | 615/1839 | 2.23 | 0.98–5.02 | 0.05 | 187/1068 | 2.71 | 1.26–5.82 | 0.01 |
TUBB3 (high/low) | 361/2010 | 2.15 | 1.27–3.62 | <0.01 | 640/NR | 2.07 | 0.91–4.68 | 0.08 | 244/1546 | 2.26 | 1.12–4.42 | 0.02 |
STMN1 (high/low) | 359/1202 | 2.34 | 1.34–4.08 | <0.01 | 291/2010 | 4.34 | 1.55–12.1 | <0.01 | 507586 | 1.71 | 0.85–3.41 | 0.12 |
Topo-II (high/low) | 1338/615 | 0.57 | 0.33–0.99 | 0.04 | 1089/1039 | 0.81 | 0.33–1.95 | 0.63 | 1338/336 | 0.52 | 0.25–1.06 | 0.07 |
TS (high/low) | 361/NR | 2.15 | 1.29–3.57 | <0.01 | 624/NR | 2.84 | 1.25–6.41 | 0.01 | 352/1047 | 1.55 | 0.77–3.14 | 0.21 |
GRP78/BiP (high/low) | 1047/5.7 | 0.59 | 0.35–0.99 | 0.04 | 1657/615 | 0.53 | 0.22–1.7 | 0.15 | 991/244 | 0.71 | 0.35–1.41 | 0.32 |
DFS | ||||||||||||
Variables | MST | HR | 95% CI | p | MST | HR | 95% CI | p | MST | HR | 95% CI | pValue |
Age, ≤69/>69 (y) | 267/733 | 0.70 | 0.42–1.17 | 0.17 | 266/759 | 1.85 | 0.88–1.89 | 0.10 | 247/733 | 1.27 | 0.62–2.62 | 0.50 |
Gender (female/male) | 539/357 | 0.63 | 0.35–1.16 | 0.14 | 444/522 | 0.92 | 0.41–2.05 | 0.83 | 753/156 | 0.42 | 0.16–1.01 | 0.07 |
p-stage (I-II/III-IV) | 890/154 | 0.21 | 0.12–0.40 | <0.01 | 499/522 | 0.48 | 0.21–1.08 | 0.07 | 890/95 | 0.05 | 0.02–0.14 | <0.01 |
ly (present/absent) | 336/890 | 1.73 | 1.03–2.88 | 0.03 | 444/1235 | 1.45 | 0.68–3.09 | 0.32 | 171/836 | 2.00 | 0.97–4.13 | 0.06 |
v (present/absent) | 443/1235 | 1.63 | 0.95–2.81 | 0.07 | 499/1235 | 1.35 | 0.61–2.97 | 0.44 | 267/NR | 1.83 | 0.85–3.95 | 0.12 |
pl (present/absent) | 267/765 | 2.04 | 1.22–3.39 | <0.01 | 411/765 | 1.86 | 0.88–3.93 | 0.09 | 187/1068 | 2.71 | 1.26–5.82 | 0.03 |
VEGFR2 (high/low) | 286/765 | 2.4 | 1.37–4.19 | <0.01 | 411/654 | 1.71 | 0.81–3.61 | 0.16 | 147/912 | 3.98 | 1.75–9.05 | <0.01 |
TUBB3 (high/low) | 357/765 | 1.65 | 0.98–2.78 | 0.05 | 443/765 | 1.37 | 0.65–2.87 | 0.39 | 247/836 | 1.97 | 0.95–4.08 | 0.06 |
STMN1 (high/low) | 336/765 | 2.46 | 1.39–4.35 | <0.01 | 286/759 | 4.25 | 1.54–11.7 | <0.01 | 336/NR | 2.08 | 1.02–4.31 | 0.04 |
Topo-II (high/low) | 443/522 | 1.03 | 0.59–1.78 | 0.92 | 443/539 | 1.38 | 0.61–3.13 | 0.60 | 340/336 | 0.90 | 0.42–1.91 | 0.78 |
TS (high/low) | 357/753 | 1.57 | 0.94–2.61 | 0.08 | 362/759 | 2.14 | 0.99–4.64 | 0.05 | 336/753 | 1.22 | 0.58–2.56 | 0.59 |
GRP78/BiP (high/low) | 444/443 | 1.09 | 0.61–1.93 | 0.30 | 1235/443 | 0.43 | 0.19–0.93 | 0.03 | 267/890 | 1.17 | 0.57–2.42 | 0.65 |
OS | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Variables | All Patients | Patients with AC Component | Patients with Non-AC Component | |||||||||
Univariate (p) | HR | 95% CI | p | Univariate (p) | HR | 95% CI | p | Univariate (p) | HR | 95% CI | p | |
Age, ≤69/>69 (y) | 0.52 | 0.48 | 0.77 | |||||||||
Gender (female/male) | 0.55 | 0.89 | 0.30 | |||||||||
p-stage (I-II/III-IV) | <0.01 | 1.62 | 1.19–2.19 | <0.01 | 0.01 | 1.67 | 1.03–2.81 | 0.03 | <0.01 | 2.63 | 1.71–4.15 | <0.01 |
Ly (present/absent) | 0.17 | 0.64 | 0.20 | |||||||||
v (present/absent) | 0.21 | 0.72 | 0.26 | |||||||||
Pl (present/absent) | 0.09 | 0.11 | 0.57 | |||||||||
VEGFR2 (high/low) | <0.01 | 1.38 | 1.05–1.81 | 0.01 | 0.05 | 0.01 | 1.64 | 1.15–2.35 | <0.01 | |||
TUBB3 (high/low) | <0.01 | 1.38 | 0.99–1.97 | 0.05 | 0.08 | 0.02 | 1.41 | 0.95–2.18 | 0.08 | |||
STMN1 (high/low) | <0.01 | 0.96 | 0.69–1.34 | 0.85 | <0.01 | 0.92 | 0.51–1.66 | 0.78 | 0.12 | |||
Topo-II (high/low) | 0.04 | 1.13 | 0.83–1.59 | 0.43 | 0.63 | 0.07 | ||||||
TS (high/low) | <0.01 | 1.43 | 0.98–2.11 | 0.05 | 0.01 | 1.71 | 0.99–2.99 | 0.05 | 0.21 | |||
GRP78/BiP (high/low) | 0.04 | 1.36 | 1.03–1.81 | 0.02 | 0.15 | 0.32 | ||||||
DFS | ||||||||||||
Variables | Univariate (p) | HR | 95% CI | p | Univariate (p) | HR | 95% CI | p | Univariate (p) | HR | 95% CI | p |
Age, ≤69/>69 (y) | 0.17 | 0.10 | 0.50 | |||||||||
Gender (female/male) | 0.14 | 0.83 | 0.07 | |||||||||
p-stage (I-II/III-IV) | <0.01 | 1.67 | 1.26–2.23 | <0.01 | 0.07 | <0.01 | 3.07 | 1.96–5.29 | <0.01 | |||
ly (present/absent) | 0.03 | 0.95 | 0.71–1.28 | 0.77 | 0.32 | 0.06 | ||||||
v (present/absent) | 0.07 | 0.44 | 0.12 | |||||||||
pl (present/absent) | <0.01 | 1.33 | 1.02–1.77 | 0.03 | 0.09 | 0.03 | ||||||
VEGFR2 (high/low) | <0.01 | 1.36 | 1.05–1.76 | 0.01 | 0.16 | <0.01 | 1.83 | 1.26–2.66 | <0.01 | |||
TUBB3 (high/low) | 0.05 | 0.39 | 0.06 | |||||||||
STMN1 (high/low) | <0.01 | 1.33 | 1.01–1.74 | 0.03 | <0.01 | 1.94 | 1.26–2.94 | <0.01 | 0.04 | |||
Topo-II (high/low) | 0.92 | 0.60 | 0.78 | |||||||||
TS (high/low) | 0.08 | 0.05 | 0.59 | |||||||||
GRP78/BiP (high/low) | 0.30 | 0.03 | 1.66 | 1.13–2.46 | 0.01 | 0.65 |
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Imai, H.; Shimizu, K.; Kawashima, O.; Endoh, H.; Imaizumi, K.; Goto, Y.; Kamiyoshihara, M.; Sugano, M.; Yamamoto, R.; Tanaka, S.; et al. Clinical Significance of Various Drug-Sensitivity Markers in Patients with Surgically Resected Pulmonary Pleomorphic Carcinoma. Cancers 2019, 11, 1636. https://doi.org/10.3390/cancers11111636
Imai H, Shimizu K, Kawashima O, Endoh H, Imaizumi K, Goto Y, Kamiyoshihara M, Sugano M, Yamamoto R, Tanaka S, et al. Clinical Significance of Various Drug-Sensitivity Markers in Patients with Surgically Resected Pulmonary Pleomorphic Carcinoma. Cancers. 2019; 11(11):1636. https://doi.org/10.3390/cancers11111636
Chicago/Turabian StyleImai, Hisao, Kimihiro Shimizu, Osamu Kawashima, Hideki Endoh, Kazuyoshi Imaizumi, Yasuhiro Goto, Mitsuhiro Kamiyoshihara, Masayuki Sugano, Ryohei Yamamoto, Shigebumi Tanaka, and et al. 2019. "Clinical Significance of Various Drug-Sensitivity Markers in Patients with Surgically Resected Pulmonary Pleomorphic Carcinoma" Cancers 11, no. 11: 1636. https://doi.org/10.3390/cancers11111636