Abstract
Nuclear KIFC1 (nKIFC1) predicts worse outcomes in breast cancer, but its prognostic value within racially distinct triple-negative breast cancer (TNBC) patients is unknown. Thus, nKIFC1 expression was assessed by immunohistochemistry in 163 African American (AA) and 144 White TNBC tissue microarrays (TMAs) pooled from four hospitals. nKIFC1 correlated significantly with Ki67 in White TNBCs but not in AA TNBCs, suggesting that nKIFC1 is not merely a surrogate for proliferation in AA TNBCs. High nKIFC1 weighted index (WI) was associated with significantly worse overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) (Hazard Ratios [HRs] = 3.5, 3.1, and 3.8, respectively; P = 0.01, 0.009, and 0.007, respectively) in multivariable Cox models in AA TNBCs but not White TNBCs. Furthermore, KIFC1 knockdown more severely impaired migration in AA TNBC cells than White TNBC cells. Collectively, these data suggest that nKIFC1 WI an independent biomarker of poor prognosis in AA TNBC patients, potentially due to the necessity of KIFC1 for migration in AA TNBC cells.
Highlights
Nuclear KIFC1 predicts worse outcomes in breast cancer, but its prognostic value within racially distinct triple-negative breast cancer (TNBC) patients is unknown
We found that Nuclear KIFC1 (nKIFC1) weighted index (WI) was significantly higher in AA than White TNBCs (154.66 vs. 133.74, respectively, p = 0.036) (Fig. 1, representative staining)
These results suggest that AA TNBC cells more heavily rely on KIFC1 for migration than EA TNBC cells, which may partly underlie the differential prognostic importance of KIFC1 by race as we found in clinical TNBC specimens
Summary
Nuclear KIFC1 (nKIFC1) predicts worse outcomes in breast cancer, but its prognostic value within racially distinct triple-negative breast cancer (TNBC) patients is unknown. A critical need exists for validation of novel biomarkers to risk-stratify AA breast cancer patients because they experience higher breast cancer mortality than any other racial group, which might indicate that high-risk AA patients are not being identified as such using standard clinical prognostic tools and are not being prescribed sufficiently aggressive treatment. The association of nKIFC1 with triple-negative receptor status and worse clinical outcomes in breast cancer suggests that nKIFC1 drives aggressive breast cancer disease course and may potentially serve as a prognostic biomarker in TNBC, its utility in specific racial groups is unclear. We analyze nKIFC1 expression by immunohistochemistry in race-annotated TNBC specimens to test its association with race, standard clinical prognostic factors, and clinical outcomes within racial groups and determine the effect of KIFC1 knockdown on migration and proliferation in White and AA TNBC cell lines
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