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

Dongping Mo,1,2 Yurong Zhu,1 Xuelian Mao,1 Cong Li,1 Yining Yang,1 Junyu Zheng,1 Feng Yan1,2 1Department of Clinical Laboratory, Jiangsu Cancer Hospital & Nanjing Medical University, Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, People’s Republic of China; 2Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, People’s Republic of ChinaCorrespondence: Dongping Mo, Department of Clinical Laboratory, Jiangsu Cancer Hospital & Nanjing Medical University, Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research, Baizi Ting No. 42, Nanjing, Jiangsu, 210009, People’s Republic of China, Email [email protected] Feng Yan, Department of Clinical Laboratory, Jiangsu Cancer Hospital & Nanjing Medical University, Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research, Baizi Ting No. 42, Nanjing, Jiangsu, 210009, People’s Republic of China, Email [email protected]: 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.Keywords: 3′tRF-Ala-AGC, neutrophil to high-density lipoprotein ratio, NHR, lymphocyte-to-monocyte ratio, LMR, lymph node metastasis, breast cancer