Expression of Serum Amyloid A and Misfolded Transthyretin Protein in Relapsed/Refractory Diffuse Large B cell Lymphoma and its Clinical Significance

Background: This study aims to evaluate the prognostic value of Serum Amyloid A (SAA) and misfolded Transthyretin (TTR) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/RDLBCL). Methods: A total of 50 DLBCL patients were included in the present study. Among these patients, 30 patients had R/R-DLBCL, 20 patients had remission/stabilization DLBCL, and 10 patients had chronic lymphadenitis. The SELDI technique, Tris-Tricine Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (Tris-Tricine-SDS-PAGE), and shotgun-LTQ-MS method were used to determine and identify the protein of SAA and TTR in R/R-DLBCL. The bioinformatics technique was used to determine the structure and function of the protein. The clinical feature data were statistically analyzed using SPSS 21.0 software, and chi-square test, Kaplan-Meier curve and logrank test ware used. Results: A molecular weight of approximately 12,000 Da and 14,000 Da were found in serum of R/R-DLBCL in protein finger graphics and Tris-Tricine-SDS-PAGE. Then, these were identified as SAA and TTR. The high expression of SAA and TTR protein (SAA+TTR+) was significantly associated with the extranodal lesion, and high level LDH and NCCN-IPI scores (P=0.017, P=0.017 and P=0.008, respectively), and correlates with the non-GCB type (the Φ correlation coefficient was 0.538) in R/R-DLBCL patients. Furthermore, the high expression of TTR protein (TTR+) was significantly associated with high levels of LDH, extranodal lesion C-MYC expression and non-GCB in R/R-DLBCL patients (The P-value was 0.028, P=0.003, the Φ correlation coefficients were 0.305 and 0.385, respectively) and the high expression of SAA protein (SAA+) was significantly associated with B-symptoms, high level of LDH and non-GCB in R/R-DLBCL patients (The P-values were 0.02, 0.011, Φ correlation coefficient was 0.390, respectively). The survival time of the SAA+ group, TTR+ group and SAA+TTR+ group were shorter than that of the negative group (P=0.001, P=0.034 and P=0.003, respectively). Multivariate analysis showed that LDH levels were an independent risk factor of poor prognosis (P<0.05). Conclusion: Both the SAA and misfolded TTR were poor prognosis factors for R/R-DLBCL.