Clinical Significance of the Serum 3'tRF-AlaAGC, Neutrophil to High-Density Lipoprotein Ratio, and Lymphocyte-to-Monocyte Ratio in Breast Cancer with Lymph Node Metastasis.

Abstract

Objective: Breast cancer (BC) is a common malignant tumor among women, the local recurrence, lymph node metastasis (LNM), and distant metastasis are the key factors affecting the prognosis of patients. tRNA-derived small RNAs (tDRs) are non-coding small RNA fragments [16-40 nucleotides (nt) in length] that play an important role in carcinogenesis and can serve as novel biological markers for the diagnosis and prognosis of various tumors. Accumulating evidence suggests that blood-based inflammatory indicators are linked with the pathogenesis of BC. However, the clinical significance of the combination of tDRs and inflammatory indicators in BC patients with LNM is still unclear.

Methods: The serum samples were collected from 175 patients with BC admitted to our hospital during June 2021 and May 2024, and 94 age-matched healthy women, and the clinical data of the research subjects were recorded. Serum 3'tRF-AlaAGC levels were measured using quantitative real-time PCR (qRT-PCR) and the blood-based inflammatory indicators were calculated from peripheral blood samples. Lasso-cox regression and multiple logistic regression were employed for variable selection. Receiver operating characteristic (ROC) was used to calculate the cut-off value of variables. Spearman correlation test was used to examine the correlation between 3'tRF-AlaAGC levels and neutrophil to HDL-C ratio (NHR), lymphocyte-to-monocyte ratio (LMR). A nomogram model for risk assessment of LNM in BC was established by using the rms package of R software.

Results: Serum 3'tRF-AlaAGC levels in BC patients with LNM were significantly higher than that in without LNM [5.17 (1.79, 16.55) vs 11.68 (2.64, 58.74), P=0.009]. The variables screened by Lasso-cox regression including 3'tRF-AlaAGC, NHR and LMR, with optimal cut-off values of 18.78, 2.94 and 5.41, respectively. NHR levels were significantly negatively associated with LMR in low 3'tRF-AlaAGC expression groups (r=-0.209, P=0.021). Multivariate logistic regression analysis confirmed that 3'tRF-AlaAGC (OR: 3.242, 95% CI: 1.583-6.641, P=0.001), NHR (OR: 3.305, 95% CI: 1.543-7.079, P=0.002), and LMR (OR: 0.329, 95% CI: 0.150-0.723, P=0.006) were independent risk factors of BC with LNM. The C-statistic of the nomograms model was 0.704, with a sensitivity of 57.14% and a specificity of 77.14%.

Conclusion: 3'tRF-AlaAGC >18.78, NHR > 2.94, and LMR ≤ 5.41 were the independent risk factors of BC with LNM. The nomogram model incorporating 3'tRF-AlaAGC, NHR and LMR can effectively predict the risk of LNM of BC patients.