# Diagnostic and Predictive Value of CD133‐Positive Circulating Tumor Cells as an Indicator of Pathological High‐Risk Factors for Stage I Non‐Small Cell Lung Cancer

**Authors:** Huandong Huo, Xiaoli Zhang, Qi Zhang, Zhuoheng Lv, Peipei Xie, Kaitai Zhang, Wen Zhang, Yousheng Mao

PMC · DOI: 10.1002/cam4.71303 · Cancer Medicine · 2025-10-29

## TL;DR

This study shows that CD133-positive circulating tumor cells can help identify high-risk stage I lung cancer patients before surgery, potentially improving treatment decisions.

## Contribution

The study introduces a diagnostic model combining CD133-positive CTCs, CT imaging, and CEA levels to predict high-risk factors in early-stage lung cancer.

## Key findings

- CD133-positive CTCs were significantly higher in patients with high-risk factors compared to those without.
- A diagnostic model using CD133-positive CTCs, CT imaging features, and CEA levels showed strong predictive accuracy.
- Patients without high-risk factors had better progression-free survival after surgery.

## Abstract

The noninvasive prediction of pathological high‐risk factors in stage I NSCLC patients before surgery remains an area for further investigation, and circulating stem cancer cells are a potential predictive diagnostic indicator. Identifying these factors preoperatively can guide treatment decisions and may improve outcomes. Here, we aim to explore CD133‐positive circulating tumor cells (CTCs) in stage I patients of NSCLC to predict pathological high‐risk factors of patients, thereby aiding clinical decision‐making.

A total of 192 Stage I NSCLC patients were finally enrolled and underwent surgical intervention. We assessed the level of CD133‐positive CTCs by employing the telomerase reverse Transcriptase‐Based CTC Detection method. The Least Absolute Shrinkage and Selection Operator method (LASSO) and logistic regression were used to analyze the association between CD133‐positive CTCs with pathological high‐risk factors and construct a diagnostic model.

Among all the enrolled patients, postoperative pathology confirmed that 12 patients had pathological high‐risk factors, while 180 patients had no high‐risk factors. The median count of CD133‐positive CTCs before surgery in patients with high‐risk factors was recorded at 1.58 ± 1.83, significantly higher than 0.767 ± 1.13 observed in the group without high‐risk factors (p = 0.048). Following feature selection by LASSO regression and multivariate logistic regression, it was determined that CD133‐positive CTCs, CT imaging nodule features, and elevated CEA levels can be combined as diagnostic indicators for pathological high‐risk factors in NSCLC patients. The ROC curve derived from internal bootstrap validation, alongside the calibration and DCA plots, affirmed the model's accuracy and predictive capability. After follow‐up, we found that patients without high‐risk pathological factors showed better PFS (p = 0.044).

This study indicated that CD133‐positive CTCs were associated with pathological high‐risk factors, and the detection of CD133‐positive CTCs may assist treatment decision‐making for patients of NSCLC.

This study explores the predictive value of combining CD133‐positive circulating tumor cells in a diagnostic model for identifying high‐risk pathological factors in stage I NSCLC. Identifying these factors preoperatively can guide treatment decisions and may improve outcomes. By integrating CD133‐positive CTCs counts with CT imaging features and CEA levels, the model supports preoperative clinical decisions, demonstrating strong predictive accuracy.

## Linked entities

- **Proteins:** PROM1 (prominin 1)
- **Diseases:** non-small cell lung cancer (MONDO:0005233), NSCLC (MONDO:0005233)

## Full-text entities

- **Genes:** CEACAM3 (CEA cell adhesion molecule 3) [NCBI Gene 1084] {aka CD66D, CEA, CGM1, CGM1a, W264, W282}, PROM1 (prominin 1) [NCBI Gene 8842] {aka AC133, CD133, CORD12, MCDR2, MSTP061, PROML1}
- **Diseases:** Tumor (MESH:D009369), Stage I (MESH:D062706), Non-Small Cell Lung Cancer (MESH:D002289)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

50 references — full list in the complete paper: https://tomesphere.com/paper/PMC12572624/full.md

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Source: https://tomesphere.com/paper/PMC12572624