Fig. 1Volcano plot of differentially expressed proteins in adrenal cortical carcinoma patients according to metastasis. TfR1, transferrin receptor.
Fig. 2Kaplan-Meier curves for overall survival based on the expression status of differentially expressed proteins. (A) Cyclin B1. (B) Transferrin receptor (TfR1). (C) Fibronectin. (D) Cyclin B1 and TfR1. (E) Cyclin B1 and fibronectin. (F) TfR1 and fibronectin. (G) Cyclin B1, TfR1, and fibronectin.
Table 1Baseline Characteristics of Adrenal Cortical Carcinoma Patients (n=46) in the TCPA Database
Characteristic |
No metastasis (n = 38) |
Metastasis (n = 8) |
Total (n = 46) |
P valuea
|
Age, yr |
47.6±14.8 |
48.0±13.1 |
47.7±14.4 |
0.948 |
Male sex |
18 (47.4) |
0 |
18 (39.1) |
0.015 |
Race |
|
|
|
0.440 |
White |
27 (71.1) |
8 (100) |
35 (76.1) |
Black |
1 (2.6) |
0 |
1 (2.2) |
Asian |
1 (2.6) |
0 |
1 (2.2) |
Unknown |
9 (23.7) |
0 |
9 (19.6) |
Survival (alive) |
30 (78.9) |
2 (25.0) |
32 (69.6) |
0.006 |
Follow-up, yr |
3.3 (1.3–5.3) |
2.2 (1.2–3.7) |
3.1 (1.3–5.3) |
0.041 |
Staging (ENSAT) |
|
|
|
<0.001 |
I |
2 (5.3) |
0 |
2 (4.3) |
II |
26 (68.4) |
0 |
26 (56.5) |
III |
10 (26.3) |
0 |
10 (21.7) |
IV |
0 |
8 (100) |
8 (17.4) |
Complete resection |
32 (84.2) |
1 (12.5) |
33 (71.7) |
<0.001 |
Chemotherapy |
25 (65.8) |
7 (87.5) |
32 (69.6) |
0.403 |
Recurrence after complete resectionb
|
11 (34.4) |
0 |
11 (33.3) |
1.000 |
Weiss scorec |
5.8±1.7 |
6.1±3.0 |
5.9±2.0 |
0.503f
|
Mitotic countd
|
|
|
|
|
Count/HPF |
9.8±8.2 |
33.0±39.9 |
13.6±18.8 |
0.589f
|
No. of >20/HPF |
2 (7.7) |
2 (28.6) |
4 (12.1) |
0.190 |
Cortisol secretione |
15 (42.9) |
5 (62.5) |
20 (46.5) |
0.440 |
Differentially expressed proteins |
|
|
|
|
High cyclin B1 |
16 (42.1) |
7 (87.5) |
23 (50.0) |
0.047 |
High TfR1 |
17 (44.7) |
6 (75.0) |
23 (50.0) |
0.243 |
High fibronectin |
15 (39.5) |
8 (100) |
23 (50.0) |
0.004 |
High cyclin B1+TfR1 |
11 (28.9) |
6 (75.0) |
17 (37.0) |
0.038 |
High cyclin B1+fibronectin |
7 (18.4) |
7 (87.5) |
14 (30.4) |
<0.001 |
High TfR1+fibronectin |
8 (21.1) |
6 (75.0) |
14 (30.4) |
0.006 |
High cyclin B1+TfR1+fibronectin |
7 (18.4) |
6 (75.0) |
13 (28.3) |
0.004 |
Table 2Cox Regression Analysis of Differentially Expressed Proteins for Overall Survival
Variable |
Univariate |
Multivariatea
|
HR (95% CI) |
P value |
HR (95% CI) |
P value |
Age (per 10-year increment) |
1.35 (0.91–2.02) |
0.140 |
- |
- |
Staging (ENSAT)b
|
11.82 (2.49–56.09) |
0.002 |
- |
- |
High cyclin B1 |
11.40 (2.47–52.59) |
0.002 |
6.13 (1.02–36.65) |
0.047 |
High TfR1 |
8.76 (1.94–39.54) |
0.005 |
6.59 (1.14–38.23) |
0.036 |
High fibronectin |
8.71 (1.93–39.35) |
0.005 |
3.92 (0.75–20.43) |
0.105 |
High cyclin B1+high TfR1c
|
22.23 (4.59–107.61) |
<0.001 |
13.72 (1.89–99.66) |
0.010 |
High cyclin B1+high fibronectinc
|
19.44 (4.22–89.57) |
<0.001 |
9.22 (1.34–63.55) |
0.024 |
High TfR1+high fibronectinc
|
21.48 (4.57–100.95) |
<0.001 |
18.59 (2.54–135.88) |
0.004 |
High cyclin B1+high TfR1+high fibronectinc
|
15.43 (4.05-58.83) |
<0.001 |
8.41 (1.54-45.90) |
0.014 |
Table 3Reclassification Analyses of the Individual Differentially Expressed Proteins and Combinations Thereof in Addition to Age and Stage for Overall Survival
|
C-index (95% CI) |
cfNRI (95% CI) |
P value (cfNRI) |
Event cfNRI |
Nonevent cfNRI |
Ref (age+stage)a
|
0.78 (0.62–0.94) |
- |
- |
- |
- |
Ref+high cyclin B1 |
0.82 (0.72–0.92) |
1.03 (0.53–1.52) |
<0.001 |
0.71 |
0.31 |
Ref+high TfR1 |
0.83 (0.71–0.94) |
1.03 (0.53–1.52) |
<0.001 |
0.71 |
0.31 |
Ref+high fibronectin |
0.82 (0.70–0.94) |
0.74 (0.16–1.32) |
0.012 |
0.43 |
0.31 |
Ref+high cyclin B1+high TfR1 |
0.84 (0.76–0.93) |
0.84 (0.34–1.34) |
0.001 |
0.71 |
0.13 |
Ref+high cyclin B1+high fibronectin |
0.86 (0.78–0.93) |
0.88 (0.34–1.43) |
0.001 |
0.57 |
0.31 |
Ref+high TfR1+high fibronectin |
0.86 (0.78–0.95) |
1.03 (0.53–1.52) |
<0.001 |
0.71 |
0.31 |
Ref+high cyclin B1+high TfR1+high fibronectin |
0.86 (0.78–0.93) |
0.88 (0.34–1.43) |
0.001 |
0.57 |
0.31 |
Table 4Cox Regression Analysis of Differentially Expressed Proteins for Overall Survival in Non-Metastatic Patients (n=38)
Variable |
Univariate |
Multivariatea
|
HR (95% CI) |
P value |
HR (95% CI) |
P value |
Age (per 10-year increment) |
1.52 (0.89–2.62) |
0.126 |
- |
- |
Staging (ENSAT)b
|
7.85 (1.33–46.04) |
0.022 |
- |
- |
High cyclin B1 |
7.75 (1.51–39.86) |
0.014 |
5.46 (0.80–37.27) |
0.083 |
High TfR1 |
11.27 (1.38–92.35) |
0.024 |
6.70 (0.70–63.77) |
0.098 |
High fibronectin |
5.91 (1.19–29.43) |
0.030 |
3.60 (0.63–20.66) |
0.150 |
High cyclin B1+high TfR1c
|
30.19 (3.45–264.24) |
0.002 |
21.69 (1.58–298.63) |
0.021 |
High cyclin B1+high fibronectinc
|
16.20 (3.07–85.37) |
0.001 |
9.25 (0.96–88.87) |
0.054 |
High TfR1+high fibronectinc
|
29.22 (3.48–245.26) |
0.002 |
84.15 (2.39–2961.35) |
0.015 |
High cyclin B1+high TfR1+high fibronectinc
|
16.20 (3.07–85.37) |
0.001 |
9.25 (0.96–88.87) |
0.054 |