A prognostic nomogram integrating novel biomarkers identified by machine learning for cervical squamous cell carcinoma.

BACKGROUND

Cervical cancer (CC) represents the fourth most frequently diagnosed malignancy affecting women all over the world. However, effective prognostic biomarkers are still limited for accurately identifying high-risk patients. Here, we provided a combination machine learning algorithm-based signature to predict the prognosis of cervical squamous cell carcinoma (CSCC).

METHODS AND MATERIALS

After utilizing RNA sequencing (RNA-seq) data from 36 formalin-fixed and paraffin-embedded (FFPE) samples, the most significant modules were highlighted by the weighted gene co-expression network analysis (WGCNA). A candidate genes-based prognostic classifier was constructed by the least absolute shrinkage and selection operator (LASSO) and then validated in an independent validation set. Finally, based on the multivariate analysis, a nomogram including the FIGO stage, therapy outcome, and risk score level was built to predict progression-free survival (PFS) probability.

RESULTS

A mRNA-based signature was developed to classify patients into high- and low-risk groups with significantly different PFS and overall survival (OS) rate (training set: p < 0.001 for PFS, p = 0.016 for OS; validation set: p = 0.002 for PFS, p = 0.028 for OS). The prognostic classifier was an independent and powerful prognostic biomarker for PFS in both cohorts (training set: hazard ratio [HR] = 0.13, 95% CI 0.05-0.33, p < 0.001; validation set: HR = 0.02, 95% CI 0.01-0.04, p < 0.001). A nomogram that integrated the independent prognostic factors was constructed for clinical application. The calibration curve showed that the nomogram was able to predict 1-, 3-, and 5-year PFS accurately, and it performed well in the external validation cohorts (concordance index: 0.828 and 0.864, respectively).

CONCLUSION

The mRNA-based biomarker is a powerful and independent prognostic factor. Furthermore, the nomogram comprising our prognostic classifier is a promising predictor in identifying the progression risk of CSCC patients.