Prognostic value of genetic aberrations and tumor immune microenvironment in primary acral melanoma.

BACKGROUND: Acral melanoma (AM) is the most common subtype in Chinese melanoma patients with a very poor prognosis. However, our understanding of the disease pathogenesis and molecular landscape is limited by the few studies that have been conducted. Here, we profiled the clinical characteristics, mutational landscapes and tumor immune microenvironment of AM patients to gain insights into disease characteristics and potential treatment strategies. METHODS: A total of 90 AM patients were enrolled and their tissue samples were subjected to next-generation sequencing and multiplexed immunohistochemistry tests. Kaplan-Meier curves and log-rank tests were used to analyze the prognostic potential of various genetic aberrations and immune cell compositions in AM. RESULTS: The median disease-free survival was 21.3 months and estimated median overall survival (OS) was 60 months. More advanced stages, older ages and thickness of greater than 4 mm were associated with worse prognosis in AM patients (HR = 2.57, 95% CI 1.25-5.29, p = 0.01; HR = 2.77, 95% CI 1.22-6.28, p = 0.02; HR = 3.43, 95% CI 1.51-7.82, p < 0.01, respectively), while patients who received post-surgical treatments had better survival (HR = 0.36, 95% CI 0.17-0.76, p = 0.01). The most frequently altered genes included BRAF (14.5%), KIT (16.9%), NRAS (12%), NF1 (10.8%), APC (7.2%), and ARID2 (6%). Copy number variations (CNV) were commonly found in CCND1 (19.3%), CDK4 (19.3%), MDM2 (14.5%) and FGF19 (12%). CDK4 amplifications was independently associated with shorter OS in AM patients (HR = 3.61, 95% CI 1.38-9.46, p = 0.01). CD8 + T cells (p < 0.001) and M1 macrophages (p = 0.05) were more highly enriched in the invasive margin than in the tumor center. Patients with higher levels of M1 macrophage infiltration in the invasive margin derived markedly longer OS (HR = 0.43, 95% CI 0.20-0.95, p = 0.03). Interestingly, in CDK4-amplified patients, there tended to be a low level of M1 macrophage infiltration in the invasive margin (p = 0.06), which likely explains the poor prognosis in such patients. CONCLUSIONS: Our study provided a comprehensive portrait of the clinicopathological features, genetic aberrations and tumor microenvironment profiles in AM patients and identified candidate prognostic factors, which may facilitate development of additional therapeutic options and better inform clinical management of AM patients. Based on these prognostic factors, further studies should focus on enhancing the infiltration of M1 macrophages, especially in CDK4-amplified AM patients.

Near-Infrared Spectroscopy Analysis of the Phytic Acid Content in Fuzzy Cottonseed Based on Machine Learning Algorithms.

Cottonseed is rich in oil and protein. However, its antinutritional factor content, of phytic acid (PA), has limited its utilization. Near-infrared (NIR) spectroscopy, combined with chemometrics, is an efficient and eco-friendly analytical technique for crop quality analysis. Despite its potential, there are currently no established NIR models for measuring the PA content in fuzzy cottonseeds. In this research, a total of 456 samples of fuzzy cottonseed were used as the experimental materials. Spectral pre-treatments, including first derivative (1D) and standard normal variable transformation (SNV), were applied, and the linear partial least squares (PLS), nonlinear support vector machine (SVM), and random forest (RF) methods were utilized to develop accurate calibration models for predicting the content of PA in fuzzy cottonseed. The results showed that the spectral pre-treatment significantly improved the prediction performance of the models, with the RF model exhibiting the best prediction performance. The RF model had a coefficient of determination in prediction (R2p) of 0.9114, and its residual predictive deviation (RPD) was 3.9828, which indicates its high accuracy in measuring the PA content in fuzzy cottonseed. Additionally, this method avoids the costly and time-consuming delinting and crushing of cottonseeds, making it an economical and environmentally friendly alternative.