# Predicting Risk of Lymph Node Metastasis in Neuroendocrine Carcinoma of Cervix: A Validated Nomogram Incorporating Neuroendocrine Markers and Clinical Parameters

**Authors:** Mingzhu Jia, Siyuan Zeng, Juan Zou, Huiling Chen, Changsheng Lin, Shuqi Yang, Jiangchuan Pi, Xue Xiao

PMC · DOI: 10.1002/cam4.71686 · 2026-03-06

## TL;DR

This study creates a model to predict lymph node metastasis risk in cervical neuroendocrine carcinoma using clinical data and biomarkers, helping identify low-risk patients.

## Contribution

A novel nomogram model combining neuroendocrine markers and clinical parameters to predict lymph node metastasis in cervical neuroendocrine carcinoma.

## Key findings

- The nomogram model achieved high accuracy with C-indexes of 0.894 and 0.92 in training and validation cohorts.
- CD56 positivity and specific clinical factors were identified as independent risk factors for lymph node metastasis.
- The model can identify low-risk patients with a risk probability threshold of 0.20.

## Abstract

Lymph node metastasis (LNM) is an important factor leading to poor prognosis of tumors. This study aims to predict the risk probability of LNM in neuroendocrine carcinoma of cervix (NECC).

202 and 92 patients were included as the training cohort and the validation cohort respectively. Logistics regression analysis was conducted to determine the risk factors related to LNM in the training cohort. The validity of the model was evaluated by the calibration curve and the consistency index. The receiver operating characteristic curve was used to determine the optimal threshold for predicting the risk of LNM. Then, it compared the predictive ability of the different models and their ability to identify low‐risk patients.

Multivariate logistic regression analysis confirmed that the depth of stromal invasion (p = 0.029), parametrium invasion (p = 0.046), lymphovascular space invasion (p = 0.011), cervical‐uterine junction invasion (p = 0.046), and positive CD56 (p = 0.008) were the independent risk factors for LNM, which were included in the construction of the nomogram model. Both the internal and external calibration curves showed that the model fits well. The C‐index of the training cohort and the validation cohort in this developed model (0.894 and 0.92, respectively) was superior to other models. The optimal threshold of risk probability of LNM predicted by the model was 0.20. Based on this threshold, this model showed a good recognition ability to identify low‐risk patients.

The nomogram model constructed by combining clinical parameters with neuroendocrine markers could effectively predict the risk probability of LNM in NECC and identify the low‐risk population.

This study creates a nomogram model to predict risk probability of lymph node metastasis in NECC based on neuroendocrine biomarkers (CD56) and clinical factors. This model is superior to other existing models through the comparison. And it enables clinicians to identify low‐risk patients (risk probability threshold: 0.20) to guide the individualized range of operation, potentially sparing them unnecessary lymphadenectomy and its associated morbidity.

## Linked entities

- **Proteins:** NCAM1 (neural cell adhesion molecule 1)

## Full-text entities

- **Genes:** ENO2 (enolase 2) [NCBI Gene 2026] {aka HEL-S-279, NSE}, CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, CHGA (chromogranin A) [NCBI Gene 1113] {aka CGA, PHE5, PHES}, RB1 (RB transcriptional corepressor 1) [NCBI Gene 5925] {aka OSRC, PPP1R130, RB, p105-Rb, p110-RB1, pRb}, NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684] {aka CD56, MSK39, NCAM}, SYNM (synemin) [NCBI Gene 23336] {aka DMN, SYN}, SYP (synaptophysin) [NCBI Gene 6855] {aka MRX96, MRXSYP, XLID96}
- **Diseases:** LNM (MESH:D008207), appendiceal neuroendocrine neoplasms (MESH:D001063), neuroendocrine tumors (MESH:D018358), lymph cysts (MESH:D003560), cervical squamous cell carcinoma (MESH:D002294), small cell carcinoma (MESH:D018288), metastasis (MESH:D009362), nerve injury (MESH:D000080902), death (MESH:D003643), cervical cancer (MESH:D002583), lymphedema (MESH:D008209), malignancy (MESH:D009369), gynecological malignancy (MESH:D005833), infection (MESH:D007239), I-III (MESH:C564683), NECC (MESH:D018278), vascular injury (MESH:D057772)
- **Chemicals:** formalin (MESH:D005557)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12965842/full.md

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Source: https://tomesphere.com/paper/PMC12965842