Data-driven phenotyping of preoperative functional decline patterns in patients undergoing lumbar decompression and lumbar fusion using smartphone accelerometry.

OBJECTIVE: Treatment of degenerative lumbar spine pathologies typically escalates to surgical intervention when symptoms begin to significantly impair patients' functional status. Currently, surgeons rely on subjective patient assessments through patient-reported outcome measures to estimate the decline in patient wellness and quality of life. In this analysis, the authors sought to use smartphone-based accelerometry data to provide an objective, continuous measurement of physical activity that might aid in effective characterization of preoperative functional decline in different lumbar spine surgical indications. METHODS: Up to 1 year of preoperative activity data (steps taken per day) from 14 patients who underwent lumbar decompression and 15 patients who underwent endoscopic lumbar fusion were retrospectively extracted from patient smartphones. A data-driven algorithm was constructed based on 10,585 unique activity data points to identify and characterize the functional decline of patients preceding surgical intervention. Algorithmic estimation of functional decline onset was compared with reported symptom onset in clinical documentation across patients who presented acutely (≤ 5 months of symptoms) or chronically (> 5 months of symptoms). RESULTS: The newly created algorithm identified a statistically significant decrease in physical activity during measured periods of functional decline (p = 0.0020). To account for the distinct clinical presentation phenotypes of patients requiring lumbar decompression (71.4% acute and 28.6% chronic) and those requiring lumbar fusion (6.7% acute and 93.3% chronic), a variable threshold for detecting clinically significant reduced physical activity was implemented. The algorithm characterized functional decline (i.e., acute or chronic presentation) in patients who underwent lumbar decompression with 100% accuracy (sensitivity 100% and specificity 100%), while characterization of patients who underwent lumbar fusion was less effective (accuracy 26.7%, sensitivity 21.4%, and specificity 100%). Adopting a less-permissive detection threshold in patients who underwent lumbar fusion, which rendered the algorithm robust to minor fluctuations above or below the chronically decreased level of preoperative activity in most of those patients, increased functional decline classification accuracy of patients who underwent lumbar fusion to 66.7% (sensitivity 64.3% and specificity 100%). CONCLUSIONS: In this study, the authors found that smartphone-based accelerometer data successfully characterized functional decline in patients with degenerative lumbar spine pathologies. The accuracy and sensitivity of functional decline detection were much lower when using non-surgery-specific detection thresholds, indicating the effectiveness of smartphone-based mobility analysis in characterizing the unique physical activity fingerprints of different lumbar surgical indications. The results of this study highlight the potential of using activity data to detect symptom onset and functional decline in patients, enabling earlier diagnosis and improved prognostication.

MicroRNA-200c and microRNA- 141 are regulated by a FOXP3-KAT2B axis and associated with tumor metastasis in breast cancer.

BACKGROUND: Members of the microRNA (miR)-200 family, which are involved in tumor metastasis, have potential as cancer biomarkers, but their regulatory mechanisms remain elusive. METHODS: We investigated FOXP3-inducible breast cancer cells, Foxp3 heterozygous Scurfy mutant (Foxp3 sf/+ ) female mice, and patients with breast cancer for characterization of the formation and regulation of the miR-200 family in breast cancer cells and circulation. Participants (259), including patients with breast cancer or benign breast tumors, members of breast cancer families, and healthy controls, were assessed for tumor and circulating levels of the miR-200 family. RESULTS: First, we identified a FOXP3-KAT2B-miR-200c/141 axis in breast cancer cells. Second, aging Foxp3 sf/+ female mice developed spontaneous breast cancers and lung metastases. Levels of miR-200c and miR-141 were lower in Foxp3 sf/+ tumor cells than in normal breast epithelial cells, but plasma levels of miR-200c and miR-141 in the Foxp3 sf/+ mice increased during tumor progression and metastasis. Third, in patients with breast cancer, the levels of miR-200c and 141 were lower in FOXP3 low relative to those with FOXP3 high breast cancer cells, especially in late-stage and metastatic cancer cells. The levels of miR-200c and miR-141 were higher in plasma from patients with metastatic breast cancer than in plasma from those with localized breast cancer, with benign breast tumors, with a family history of breast cancer, or from healthy controls. Finally, in Foxp3 sf/+ mice, plasma miR-200c and miR-141 appeared to be released from tumor cells. CONCLUSIONS: miR-200c and miR-141 are regulated by a FOXP3-KAT2B axis in breast cancer cells, and circulating levels of miR-200c and miR-141 are potential biomarkers for early detection of breast cancer metastases.

CD24 is a genetic modifier for risk and progression of prostate cancer.

CD24 plays an oncogenic role in the onset and progression of various human cancers, including prostate cancer. In the present study, we identified two linkage disequilibrium blocks with four recombination hotspot motifs in human CD24 locus. To elucidate whether genetic variants of CD24 are associated with susceptibility to prostate cancer and its disease status, we conducted a case-control association study with two P170 C/T and P-534 A/C polymorphisms of CD24 in 590 patients with prostate cancer and 590 healthy controls. A significant increased risk of prostate cancer was found in men with the P170T/T genotype over the P170C/C genotype (odd ratio = 1.74, 95% confidence interval = 1.16-2.63, P = 0.008), and in men with the P-534C/C genotype over the P-534A/A genotype (odd ratio = 1.47, 95% CI = 1.18-2.26, P = 0.003). Cochran-Armitage trend analysis showed that the P170T allele was significantly correlated with an increased risk of prostate cancer progression (P = 0.029, trend between genotypes and stages) and this observation was also validated in an independent sample cohort. Next, we found that tumors with P170T or P-534C alleles had more twofold increased protein expressions of CD24 as compared to those with P170C or P-534A alleles, respectively. Likewise, tumors with a combination of P170T/T and P-534C/C genotypes were associated with a high mRNA level of CD24. Our data suggest a significant association of CD24 genetic variants with prostate cancer onset and progression, which provides new insight into molecular genetics of prostate cancer; however, these findings need to be validated in multiple independent cohorts. © 2016 Wiley Periodicals, Inc.