Expressions of YAP1, YTHDF2 and miR-888-3p in patients undergoing radical resection for lung cancer and their predictive value for short-term prognosis
10.3760/cma.j.cn115355-20230627-00334
- VernacularTitle:行肺癌根治术患者YAP1、YTHDF2、miR-888-3p表达及其对近期预后的预测价值
- Author:
Kang ZHENG
1
;
Yunfeng BO
;
Guanhua LIU
Author Information
1. 山西省肿瘤医院 中国医学科学院肿瘤医院山西医院 山西医科大学附属肿瘤医院胸外科，太原 030013
- Keywords:
Lung neoplasms;
Prognosis;
Influencing factors;
Prediction model
- From:
Cancer Research and Clinic
2023;35(9):646-652
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the expressions of Yes-associated protein 1 (YAP1), YTH domain-containing family protein 2 (YTHDF2) and microRNA-888-3p (miR-888-3p) in patients undergoing radical resection for lung cancer, and their predictive value for short-term prognosis of patients.Methods:A total of 420 lung cancer patients who underwent radical resection for lung cancer in Shanxi Province Cancer Hospital from May 2015 to May 2022 were selected and divided into a modeling set (280 cases) and a validation set (140 cases) in a ratio of 2∶1 by using the computer-generated random number method. The paracancerous normal lung tissues removed by surgery (>5 cm from the edge of the cancer tissues) were used as the control. The relative expressions of YAP1 and YTHDF2 proteins in cancer tissues and paracancerous tissues of the modeling set was detected by Western blotting, and the relative expression of miR-888-3p was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). The patients were followed up for 1 year to analyze the prognosis, and the patients in the modeling set who had recurrence, metastasis or cancer-caused death were considered as the poor prognosis group, and the rest of the patients were considered as the good prognosis group. The relative expressions of YAP1 protein, YTHDF2 protein, miR-888-3p and general information of the patients in the two groups were compared; the Cox proportional hazards model was used to analyze the influencing factors of the short-term prognosis of radical resection for lung cancer in the modeling set; a Nomogram prediction model was constructed for the short-term prognosis of radical resection for lung cancer, and its efficacy was verified.Results:The relative expression of miR-888-3p in the modeling set of cancer tissues and paracancerous tissues was 0.49±0.08 and 0.16±0.05, and the difference was statistically significant ( t = 58.53, P < 0.001); the relative expression of YAP1 protein was 0.48±0.06 and 0.12±0.03, and the difference was statistically significant ( t = 89.80, P < 0.001); the relative expression of YTHDF2 protein was 0.23±0.04 and 0.59±0.07, and the difference was statistically significant ( t = 74.72, P < 0.001). After 1 year of follow-up in the modeling set, 32 cases were lost, and 81 (32.66%) of the remaining 248 cases had a poor prognosis (poor prognosis group), while 167 cases (67.34%) were in the good prognosis group. Compared with the good prognosis group, the relative expressions of YAP1 protein and miR-888-3p in cancer tissues was elevated in the poor prognosis group (both P < 0.05), and the relative expression of YTHDF2 protein was decreased ( P < 0.05); the proportions of patients with smoking, coronary artery disease, TNM stage Ⅲ-Ⅳ, maximum tumor diameter ≥ 5 cm, and undifferentiated/lowly differentiated tissues were high in the poor prognosis group, the physical status (PS) score was elevated, and the proportion of patients with regular postoperative radiotherapy was reduced (all P < 0.05). The results of multivariate Cox regression analysis showed that the proportion of patients with smoking ( HR = 2.098, 95% CI 1.143-3.852, P = 0.009), TNM stage ( HR = 2.421, 95% CI 1.350-4.341, P = 0.002), maximum tumor diameter ( HR = 1.883, 95% CI 1.036-3.424, P = 0.011), degree of tissue differentiation ( HR = 3.133, 95% CI 1.590-6.173, P < 0.001), regular postoperative radiotherapy ( HR = 0.417, 95% CI 0.219-0.797, P = 0.003), YAP1 ( HR = 7.043, 95% CI 2.842-17.452, P < 0.001), YTHDF2 ( HR = 0.560, 95% CI 0.418-0.752, P < 0.001), and miR-888-3p ( HR = 4.100, 95% CI 1.789-9.394, P < 0.001) were the independent influencing factors for the short-term prognosis of radical resection for lung cancer. A Nomogram prediction model was constructed, and internal validation showed that the consistency index of the model was 0.822 (95% CI 0.774-0.870); the result of receiver operator characteristic curve showed that the sensitivity of the Nomogram prediction model for predicting the short-term prognosis of radical resection for lung cancer in the modeling set was 97.5% (95% CI 86.8%-99.9%), and the specificity was 82.4% (95% CI 73.0%-89.6%), and the area under the curve (AUC) was 0.943 (95% CI 0.889-0.976); the sensitivity of predicting the short-term prognosis of radical resection for lung cancer in the validation set was 91.53% (95% CI 81.3%-97.2%), and the specificity was 81.5% (95% CI 71.3%-89.2%), and the AUC was 0.922 (95% CI 0.865-0.961). Conclusions:YAP1, YTHDF2 and miR-888-3p are all influencing factors for short-term prognosis of radical resection for lung cancer, and the Nomogram prediction model constructed based on these factors has good predictive efficacy for the short-term prognosis of radical resection for lung cancer.
