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.

Immune and stromal transcriptional patterns that influence the outcome of classic Hodgkin lymphoma

“…1 ). Consistent with previous findings, we identified VEGFA , SPP1 , TREM1 10 , NOS2 11 , S100A8 , S100A9 12 , LILRB2 13 , and LYZ 14 genes (among others) as being enriched in relapsed or U patients. However, the information derived from analyses using individual genes is limited and diffuse and does not allow conclusions to be drawn about biological significance, so we added extra deconvolution steps to facilitate phenotypic characterization with the ssGSEA and CIBERSORTx tools.…”

Immune and stromal transcriptional patterns that influence the outcome of classic Hodgkin Lymphoma

“…1). Consistent with previous ndings, we identi ed VEGFA, 10 SPP1, 10 TREM1, 10 NOS2, 11 S100A8, S100A9, 12 LILRB2, 13 and LYZ 14 genes (among others) as being enriched in relapsed or U patients. However, the information derived from analyses using individual genes is limited and diffuse and does not allow conclusions to be drawn about biological signi cance, so we added extra deconvolution steps to facilitate phenotypic characterization with the ssGSEA and CIBERSORTx tools.…”