Combined Identification of Novel Markers for Diagnosis and Prognostic of Classic Hodgkin Lymphoma

Abstract

Background

An effective diagnostic and prognostic marker based on the gene expression profile of classic Hodgkin lymphoma (cHL) has not yet been developed. The aim of the present study was to investigate potential markers for the diagnosis and prediction of cHL prognosis.

Methods

The gene expression profiles with all available clinical features were downloaded from the Gene Expression Omnibus (GEO) database. Then, multiple machine learning algorithms were applied to develop and validate a diagnostic signature by comparing cHL with normal control. In addition, we identified prognostic genes and built a prognostic model with them to predict the prognosis for 130 patients with cHL which were treated with first-line treatment (ABVD chemotherapy or an ABVD-like regimen).

Results

A diagnostic prediction signature was constructed and showed high specificity and sensitivity (training cohort: AUC=0.981,95% CI 0.933–0.998, P<0.001, validation cohort: AUC=0.955,95% CI 0.895–0.986, P<0.001). Additionally, nine prognostic genes (LAMP1, STAT1, MMP9, C1QB, ICAM1, CD274, CCL19, HCK and LILRB2) were screened and a prognostic prediction model was constructed with them, which had been confirmed effectively predicting prognosis (P<0.001). Furthermore, the results of the immune infiltration assessment indicated that the high scale of the fraction of CD8 + T cells, M1 macrophages, resting mast cells associated with an adverse outcome in cHL, and naive B cells related to prolonged survival. In addition, a nomogram that combined the prognostic prediction model and clinical characteristics is also suggested to have a good predictive value for the prognosis of patients.

Conclusion

The new markers found in this study may be helpful for the diagnosis and prediction of the prognosis of cHL.

Keywords:

• novel markers
• diagnosis
• prognosis
• classic Hodgkin lymphoma

Data Sharing Statement

All data generated or analyzed during this study are included in this article.

Ethics Approval and Consent to Participate

The need for ethics approval was waived by the Department of Scientific Research Management, Changzhou Tumor Hospital Affiliated to Soochow University.

Acknowledgments

This work was supported by a grant from Startup Fund for scientific research, Fujian Medical University (2018QH1171). And all authors would like to thank Christian Steidl, MD, for sharing survival information of dataset GSE17920.

Disclosure

The authors declare that they have no competing interests.