Construction of a TFF3-Related Prognostic Model for Lung Adenocarcinoma Based on Lasso-Cox Regression and Its Predictive Value for Immunotherapy

Corresponding author: YOU Qing-hai, amormor@126.com

DOI: 10.12201/bmr.202509.00054

•  

  Abstract: Objective To construct a prognostic model of Lung Adenocarcinoma (LUAD) related to intestinal Trefoil Factor 3 (TFF3) and evaluate the predictive value of this model for immunotherapy. Methods　 Tumor immune estimation resource(TIMER), UALCAN，and CPTAC databases were utilized to analyze TFF3 expression and its correlation with LUAD staging. The tumor immune single cell hub(TISCH) database was employed to examine TFF3 expression across different cell types within lung cancer tissues，followed by localization analysis. Immunohistochemical expression of TFF3 in LUAD tissues was analyzed using the human protein atlas (HPA) database. LUAD patients in the cancer genome atlas (TGCA) database were stratified into two groups based on TFF3 expression levels. Differential gene expression analysis identified TFF3-associated differentially expressed genes. Univariate survival analysis and Lasso-Cox regression were then employed to construct TFF3-related LUAD prognostic signatures and their risk score calculation formulas. The predictive efficacy of these signatures was evaluated using Kaplan-Meier curves and receiver operating characteristic (ROC) curves. A LUAD prognostic nomogram was established based on risk score，T stage，N stage，age，and gender to enable intuitive prediction of LUAD prognosis using parameters including risk score. Results　TFF3 mRNA and protein expression were higher in LUAD tissues than in normal controls，with increased expression correlating with higher LUAD staging. Single-cell data analysis revealed TFF3 expression primarily localized to tumor cells within LUAD tissues, with negligible expression in immune cells and other cell types. Immunohistochemistry confirmed TFF3 expression predominantly occurred within LUAD tumor cells. Differential analysis identified 600 TFF3-associated differentially expressed genes. Univariate analysis further selected 12 differentially expressed genes with prognostic value. Using Lasso-Cox regression，an 8-gene TFF3-associated prognostic signature was constructed. The calculated risk scores showed that LUAD patients in the low-risk group had significantly better overall prognosis than those in the high-risk group (P<0.001)，with good sensitivity and specificity. Risk scores increased with LUAD stage progression. A risk-score-based nomogram, integrated with clinical parameters, effectively predicted patient prognosis. Conclusion　The TFF3-based prognostic model not only predicts overall survival but also forecasts immunotherapy efficacy.

  Key words: Lung adenocarcinoma; TFF3; Immune checkpoint inhibitor; Nomogram; Lasso-Cox regression

  Submit time: 26 September 2025

  Copyright: The copyright holder for this preprint is the author/funder, who has granted biomedRxiv a license to display the preprint in perpetuity.
• html

• 图表

• WangZhiyuan, Mengling, Shijuan, LiuYuanyuan, LiRuidi, LiWenxin, AnShuhong. Expression and the role of TFF3 in lung adenocarcinoma based on bioinformatics analysis. 2024. doi: 10.12201/bmr.202403.00019

  Wang Huan, Ma Ying, Tian Jingnan, Lu Yi. Progress in the Diagnosis and Treatment of Immune Checkpoint Inhibitor-Associated Hypothyroidism from the Perspectives of Traditional Chinese and Western Medicine. 2025. doi: 10.12201/bmr.202505.00004

  QIAN Yun. Adverse events associated with immune checkpoint inhibitors: clinical manifestations and mechanisms. 2025. doi: 10.12201/bmr.202502.00010

  Li Ying, Wang Xiaofei, Lu Shengwei, Dong Danni, Zhang Jingfeng, Zheng Jianjun. CT Findings and Clinical Features of checkpoint Inhibitor-related pneumonitis. 2024. doi: 10.12201/bmr.202407.00008

  liushunlin. The expression of CPNE1 and ZWILCH in the progression of lung adenocarcinoma and their correlation with prognosis. 2024. doi: 10.12201/bmr.202406.00030

  Tian Lin. Professor Tian Lins Experience Sharing and Case Studies in the Treatment of Lung Adenocarcinoma. 2025. doi: 10.12201/bmr.202506.00019

  HeXin, ChenFang, Zhou Xiaoqi, Cheng Jie, Tang Qiqun, Cheng Xiaohua, Guo Zonghai, Zhou Ran. Prognostic Value of systemic immune inflammation index and rSIG shock index in elderly patients with ICH. 2025. doi: 10.12201/bmr.202509.00020

  JIANG Shali. Research on the Expression of SLPI in Cervical Adenocarcinoma and Its Correlation with HPV Infection. 2025. doi: 10.12201/bmr.202505.00012

  HE Lanlan, LI Danyang, SHEN Li, WU Zhonghua, ZHANG Jun, YE Yongqiang. Construction and validation of nomogram model for prolonged length of stay in patients with acute cerebral infarction based on total cerebral small vessel disease burden scores. 2025. doi: 10.12201/bmr.202501.00008

  付思思. Construction and validation of Nomogram analysis model for nausea and vomiting after lobectomy in non-small cell lung cancer patients. 2025. doi: 10.12201/bmr.202507.00001

• ID	Submit time	Number	Download
  1	2025-09-16	10.12201/bmr.202509.00054V1	Download

• Public  Anonymous  To author only Submit Comments