Low Expression of CD5 and CD6 Is Associated with Poor Overall Survival for Patients with T-Cell Malignancies

Abstract

Background: T-cell malignancies (TCMs), including T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoma (TCL), are highly aggressive and have a poor prognosis. To further understand prognostic stratifications and to design targeted therapies, this study aims to explore novel, potential biomarkers based on alterations in immune costimulatory molecules (CMs) for TCMs.

Methods: Peripheral blood from 25 de novo T-ALL patients in our clinical center and transcriptome data from 131 to 162 patients with peripheral TCL (PTCL) from the GSE19069 and GSE58445 dataset, respectively, were obtained to assess the expression levels of CMs and their prognostic significance.

Results: Seven CMs were associated with overall survival (OS). Among these CMs, CD5 and CD6 had the highest pairwise positive correlation (R = 0.69). CD5 and CD6 were significantly down-regulated in TCM patients compared with healthy individuals (HIs), and lower CD5 and CD6 expression was associated with poor OS for both T-ALL and TCL patients, particularly for patients greater than 60 years old. Furthermore, CD5 was positively correlated with CD6 in TCM patients. Compared with patients who were CD5^highCD6^high, T-ALL and TCL patients who were CD5^lowCD6^low had poor OS. Importantly, CD5^highCD6^high was an independent prognostic predictor for OS in T-ALL (HR = 0.39, 95% CI: 0.23-0.65, P < 0.001) and TCL (HR = 0.35, 95% CI: 0.19-0.62, P < 0.001) patients.

Conclusions: Low expression of CD5 and CD6 was associated with poor OS for TCM patients, and this may be a potential immune biomarker panel for prognostic stratification of TCM patients.

Figure 1

Schematics of the study. Patients with T-cell malignancies (TCMs) were divided into training (T-cell acute lymphoblastic leukemia; T-ALL) and validation (T-cell lymphoma; TCL) cohorts. Peripheral blood from T-ALL patients in the training cohort was collected for ribonucleic acid (RNA) extraction and quantitative real-time polymerase chain reaction (qRT-PCR) to detect the expression levels of CD5 and CD6. Then, the relationship between CD5 and CD6 with overall survival (OS) and co-expression of CD5/CD6 for risk stratification was analyzed. Finally, gene expression omnibus (GEO) datasets, acting as a validation cohort, were used to validate the results in the training cohort.

Figure 2

OS analysis of CD5 and CD6 in TCM patients in the training and validation cohorts. (a-b) Comparison of the CD5 and CD6 expression levels in healthy individuals (HIs) and T-ALL (a) or TCL (b) patients. (c-d) After the cut-off values were determined by X-tile software (left panel), Kaplan–Meier curves (right panel) were plotted according to subgroups of low and high CD5 expression in the training (c) and validation (d) cohorts. (e-f) Based on the cut-off values for CD6 (left panel), the TCM patients were divided into low and high CD6 expression groups, and the Kaplan–Meier curves (right panel) were plotted in the training (e) and validation (f) cohorts.

Figure 3

OS analysis of the CD5 and CD6 ratios in the training and validation cohorts. (a-b) OS analysis was performed with the dichotomized relative expression ratios of CD5/CD3E, CD5/CD3G, CD5/CD3D, CD5/CD247, CD5/CD4, CD5/CD8A, CD5/CD8B (a) and the CD6/CD3E, CD6/CD3G, CD6/CD3D, CD6/CD247, CD6/CD4, CD6/CD8A, CD6/CD8B ratios (b) in the training (left panel) and validation (right panel) cohorts.

Figure 4

Co-expression of CD5 and CD6 for prognostic stratification in TCM patients. (a) Correlation between the CD5 and CD6 expression levels in the training (left panel) and validation (right panel) cohorts. (b) Kaplan–Meier curves for patients who were CD5^highCD6^high or CD5^lowCD6^low in the training (left panel) and validation (right panel) cohorts. (c) Distribution of the OS time for patients who were CD5^highCD6^high or CD5^lowCD6^low in the training (left panel) and validation (right panel) cohorts.