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Objectives <p>Assessing the prognosis of patients with “driver-gene-negative” lung adenocarcinoma (LUAD patients negative for EGFR, KRAS, BRAF, HER2, MET, ALK, RET and ROS1 were identified as “driver-gene-negative”) is of significant clinical importance. We aimed to devise a prognostic nomogram for this LUAD subgroup and to define its biological basis.</p> Materials and methods <p>Prognostic nomogram were established based on a retrospective study of 294 patients with surgical resected “driver-gene-negative” LUAD at The First Affiliated Hospital of Sun Yat-sen University between September 2003 and June 2015. The concordance index (C-index) and calibration curve were used to determine its predictive accuracy and discriminatory capacity. Patients were classified into low- and high-risk subgroups according to nomogram scores. To define the biological basis, gene set enrichment analysis was carried out in an independent dataset of 49 “driver-gene-negative” LUAD patients.</p> Results <p>The nomogram built on the independent factors including CTC, age and stage achieved C-index of 0.785 [95% confidence interval (CI) 0.753–0.817] for predicting OS of “driver-gene-negative” LUAD. The calibration curves for OS probabilities showed a good agreement between the nomogram prediction and actual observation. High-risk patients had shorter OS [hazard ratio (HR) = 7.43, 95% CI 5.20-10.42, <i>p</i> &lt; 0.0001]. The genetic analysis suggested the biological basis for the role of the predictive model may be due to changes in cell proliferation, metabolism and neurological disease, indicating a relationship between increased proliferative potential and preferential poor prognosis.</p> Conclusions <p>The prognostic nomogram showed promising prediction efficacy and is expected to predict the prognosis of “driver-gene-negative” LUAD. The easy-to-use nomogram and the enriched pathways can help clinical decision-making, guide follow-up planning, and develop new therapeutic targets.</p>

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A prognostic nomogram for overall survival in patients with driver-gene-negative lung adenocarcinoma and its biological basis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月14日

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  • Shi-Chao Shan,
  • Hao-Shuai Yang,
  • Qi-Kun Guo,
  • Zhen-Guo Liu,
  • Dan-Dan Chang,
  • Hong-He Luo,
  • Yi-Yan Lei,
  • Ying Zhu,
  • Jian-Jun Lu

摘要

Objectives

Assessing the prognosis of patients with “driver-gene-negative” lung adenocarcinoma (LUAD patients negative for EGFR, KRAS, BRAF, HER2, MET, ALK, RET and ROS1 were identified as “driver-gene-negative”) is of significant clinical importance. We aimed to devise a prognostic nomogram for this LUAD subgroup and to define its biological basis.

Materials and methods

Prognostic nomogram were established based on a retrospective study of 294 patients with surgical resected “driver-gene-negative” LUAD at The First Affiliated Hospital of Sun Yat-sen University between September 2003 and June 2015. The concordance index (C-index) and calibration curve were used to determine its predictive accuracy and discriminatory capacity. Patients were classified into low- and high-risk subgroups according to nomogram scores. To define the biological basis, gene set enrichment analysis was carried out in an independent dataset of 49 “driver-gene-negative” LUAD patients.

Results

The nomogram built on the independent factors including CTC, age and stage achieved C-index of 0.785 [95% confidence interval (CI) 0.753–0.817] for predicting OS of “driver-gene-negative” LUAD. The calibration curves for OS probabilities showed a good agreement between the nomogram prediction and actual observation. High-risk patients had shorter OS [hazard ratio (HR) = 7.43, 95% CI 5.20-10.42, p < 0.0001]. The genetic analysis suggested the biological basis for the role of the predictive model may be due to changes in cell proliferation, metabolism and neurological disease, indicating a relationship between increased proliferative potential and preferential poor prognosis.

Conclusions

The prognostic nomogram showed promising prediction efficacy and is expected to predict the prognosis of “driver-gene-negative” LUAD. The easy-to-use nomogram and the enriched pathways can help clinical decision-making, guide follow-up planning, and develop new therapeutic targets.