Kinesin Family Member C1 (KIFC1/HSET) Underlies Aggressive Disease in Androgen Receptor-Low and Basal-Like Triple-Negative Breast Cancers
Abstract
:1. Introduction
2. Results
2.1. AR-Low Tumors Display Aggressive Clinical Features Compared to AR-High Tumors in TNBC
2.2. KIFC1 RNA Levels Are Upregulated in AR-Low vs. AR-High TNBC Tumors
2.3. KIFC1 RNA Is Upregulated in Black/AA and Premenopausal AR-Low Tumors
2.4. High KIFC1 Levels Are Associated with a Poorer Prognosis among AR-Low Patients
2.5. Genes Driving Centrosome Amplification Are Upregulated in AR-Low TNBCs Compared to AR-High TNBCs
3. Discussion
4. Materials and Methods
4.1. Study Populations
4.2. Statistical Analyses
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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AR Higher 50% (N = 58) 1 | AR Lower 50% (N = 57) | Total (N = 115) | p-Value 2 | |
---|---|---|---|---|
KIFC1 | 22.9 (1.04–86.62) | 30.02 (10.1–72.1) | 26.49 (1.04–86.62) | 0.0029 |
AR | 2.22 (0.62–56.7) | 0.28 (0.03–0.58) | 0.62 (0.03–56.71) | Not applicable |
Age At Diagnosis (years) | 55 (29–90) | 53 (38–82) | 54 (29–90) | 0.871 |
Race | 0.690 | |||
Asian | 4 (7) | 4 (7) | 8 (7) | |
Black or African American | 17 (29) | 15 (26) | 32 (28) | |
White | 32 (55) | 36 (63) | 68 (59) | |
NA | 5 (9) | 2 (4) | 7 (6) | |
TNM_T_stage | 1.000 | |||
M0 | 49 (84) | 49 (86) | 98 (85) | |
M1 | 1 (2) | 1 (2) | 2 (2) | |
MX | 8 (14) | 7 (12) | 15 (13) | |
TNM_N_stage | 0.764 | |||
N0 | 36 (62) | 38 (67) | 74 (64) | |
N1 | 12 (21) | 13 (23) | 25 (22) | |
N2 | 7 (12) | 5 (9) | 12 (10) | |
N3 | 3 (5) | 1 (2) | 4 (3) | |
Overall_stage | 0.366 | |||
Missing | 3 (0) | 4 (0) | 7 (6.1) | |
Stage I | 12 (22) | 7 (13) | 19 (17) | |
Stage II | 32 (58) | 39 (74) | 71 (62) | |
Stage III | 10 (18) | 6 (11) | 16 (14) | |
Stage IV | 1 (2) | 1 (2) | 2 (2) | |
Tumor subtype | <0.001 | |||
Basal | 30 (52) | 54 (95) | 84 (73) | |
Other | 28 (48) | 3 (5) | 31 (27) | |
Lymph-Node-Positive Number Group | 0.685 | |||
0 | 31 (63) | 37 (67) | 68 (59) | |
≥1 | 18 (37) | 18 (33) | 36 (31) | |
Missing | 9 (0) | 2 (0) | 11 (10) | |
Lymph-Node-Positive Number | 0 (0–14) | 0 (0–10) | 0 (0–14) | 0.509 |
Menopause Status | 0.061 | |||
Perimenopausal | 1 (2) | 4 (7) | 5 (4) | |
Postmenopausal | 36 (62) | 33 (58) | 69 (60) | |
Premenopausal | 19 (33) | 11 (19) | 30 (26) | |
Indeterminate | 0 (0) | 2 (4) | 2 (2) | |
NA | 2 (4) | 7 (12) | 9 (8) |
AR Higher 50% (N = 149) 1 | AR Lower 50% (N = 150) | Total (N = 299) | p-Value 2 | |
---|---|---|---|---|
KIFC1 | 7.30 (5.53–9.14) | 7.94 (6–10) | 7.69 (5.53–9.68) | <0.001 |
AR | 6.62 (5.88–10.16) | 5.67 (5.22–5.87) | 5.87 (5.22–10.16) | Not applicable |
Age at Diagnosis (years) | 57 (27–96) | 54 (28–85) | 56 (27–96) | 0.032 |
Menopausal time point | 0.127 | |||
Post | 102 (69) | 90 (60) | 192 (64) | |
Pre | 47 (32) | 60 (40) | 107 (36) | |
PAM50 Subtype | <0.001 | |||
Basal | 56 (38) | 95 (63) | 151 (51) | |
Others | 93 (62) | 55 (37) | 148 (50) | |
The Nottingham Prognostic Index (NPI) | 4 (2–6) | 4 (1–6) | 4 (1–6) | 0.820 |
Grade | 0.026 | |||
Grade 1 or 2 | 26 (18) | 13 (9) | 39 (13) | |
Grade 3 | 122 (82) | 135 (91) | 257 (86) | |
Missing | 1 (0) | 2 (0) | 3 (1) | |
Tumor size (mm) | 22 (1–182) | 25 (0–84) | 25 (0–182) | 0.552 |
Tumor Stage | 0.098 | |||
1 | 35 (24) | 27 (18) | 62 (21) | |
2 | 62 (42) | 68 (45) | 130 (43) | |
3 | 17 (11) | 8 (5) | 25 (8) | |
null | 35 (23) | 47 (31) | 82 (27) | |
Chemotherapy | 0.453 | |||
No | 74 (50) | 68 (45) | 142 (47) | |
Yes | 75 (50) | 82 (55) | 157 (53) |
Variables | AR Lower 50%, N = 278 1 | AR Higher 50%, N = 278 1 | Overall, N = 556 1 | p-Value 2 |
---|---|---|---|---|
AR | −0.00285 (−0.01445, −0.00155) | 0.00015 (−0.00155, 0.00837) | −0.00155 (−0.01445, 0.00837) | Not applicable |
KIFC1 | 0.003 (−0.009, 0.009) | 0.001 (−0.009, 0.007) | 0.002 (−0.009, 0.009) | <0.001 |
KIFC1 Quartile | <0.001 | |||
KIFC1 Q1 | 36 (13) | 103 (37) | 139 (25) | |
KIFC1 Q2 | 66 (24) | 73 (26) | 139 (25) | |
KIFC1 Q3 | 82 (29) | 57 (21) | 139 (25) | |
KIFC1 Q4 | 94 (34) | 45 (16) | 139 (25) | |
Age at diagnosis (years) | 50 (28, 82) | 53 (29, 88) | 51 (28, 88) | 0.003 |
Missing | 53 | 77 | 130 | |
Lymph node status | <0.001 | |||
Negative | 146 (77) | 118 (61) | 264 (69) | |
Positive | 43 (23) | 74 (39) | 117 (31) | |
Missing | 89 | 86 | 175 | |
Tumor size | >0.999 | |||
Up to 1 cm | 8 (25) | 8 (25) | 16 (25) | |
>1 cm | 24 (75) | 24 (75) | 48 (75) | |
Missing | 246 | 246 | 492 | |
Histological grade | <0.001 | |||
Grade 1 or 2 | 39 (17) | 78 (36) | 117 (26) | |
Grade 3 | 189 (83) | 139 (64) | 328 (74) | |
Missing | 50 | 61 | 111 | |
Chemotherapy treatment | 0.476 | |||
No | 3 (9.1) | 6 (18) | 9 (13) | |
Yes | 30 (91) | 28 (82) | 58 (87) | |
Missing | 245 | 244 | 489 |
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Jinna, N.; Yuan, Y.-C.; Rida, P. Kinesin Family Member C1 (KIFC1/HSET) Underlies Aggressive Disease in Androgen Receptor-Low and Basal-Like Triple-Negative Breast Cancers. Int. J. Mol. Sci. 2023, 24, 16072. https://doi.org/10.3390/ijms242216072
Jinna N, Yuan Y-C, Rida P. Kinesin Family Member C1 (KIFC1/HSET) Underlies Aggressive Disease in Androgen Receptor-Low and Basal-Like Triple-Negative Breast Cancers. International Journal of Molecular Sciences. 2023; 24(22):16072. https://doi.org/10.3390/ijms242216072
Chicago/Turabian StyleJinna, Nikita, Yate-Ching Yuan, and Padmashree Rida. 2023. "Kinesin Family Member C1 (KIFC1/HSET) Underlies Aggressive Disease in Androgen Receptor-Low and Basal-Like Triple-Negative Breast Cancers" International Journal of Molecular Sciences 24, no. 22: 16072. https://doi.org/10.3390/ijms242216072