Association of expression of pSTAT3, pAKT1 with the survival of patients with diffuse large B-cell lymphoma

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Abstract


Aim. To assess the relationship between isolated and combined expression of pSTAT3, pACT1 in tumor cells with the survival of patients with diffuse large B-cell lymphoma (DLBCL).

Methods. The study included 100 patients with the first diagnosed diffuse large B-cell lymphoma, observed in the institute's clinic between 2010 and 2018 who received standard first-line R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy. The relative number of expressing pSTAT3 and pAKT1 ­tumor cells was determined by using immunohistochemical and morphometric methods. The optimal cut-off level of expression on tumor cells estimated by using receiver operating characteristic (ROC) curve analysis for pSTAT3 was 68% and for pACT1 — 70%. Given these values, all patients with DLBCL were divided into groups with a high and low degree of expression of the biomarkers. As a result, 53 patients were enrolled in the pSTAT3 high expression group (≥68% tumor cells) and 47 patients to the pSTAT3 low expression group (<68% tumor cells). Spearman’s correlation coefficient was used to examine relationships. Overall survival and event-free survival were estimated by Kaplan–Meier curves. The log-rank test was used for groups comparison.

Results. The five-year overall survival rate in the pSTAT3 high expression group was 55% versus 87% in the low expression group, p=0.015. A significant difference was found in the assessment of event-free survival: 43% for the group of pSTAT3 high expression, 66% for the group of low expression, p=0.011. A statistically significant value of a high level of pACT1 expression was revealed for 5-year overall and event-free survival (p <0.001 and p=0.003). Overall survival rate was 81% for the pACT1 low expression group and 43% for the high expression group while event-free survival rate was 64 and 41%, respectively. Also, patients with рАКТ1+/рSTAT3+ (high level) co-expression had extremely low rates of overall and event-free survival rates compared with the рАКТ1–/рSTAT3– (low ­level) group (p=0.001; p <0.001).

Conclusion. The pSTAT3 and pAKT1 biomarkers can be used as additional prognosis criteria for diffuse large B-cell lymphoma.


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About the authors

E V Vaneeva

Kirov Scientific Research Institute of Hematology and Blood Transfusion of the Federal Medical and Biological Agency

Author for correspondence.
Email: vaneeva.elena.vic@mail.ru

Russian Federation, Kirov, Russia

V A Rosin

Kirov Scientific Research Institute of Hematology and Blood Transfusion of the Federal Medical and Biological Agency

Email: vaneeva.elena.vic@mail.ru

Russian Federation, Kirov, Russia

D A Dyakonov

Kirov Scientific Research Institute of Hematology and Blood Transfusion of the Federal Medical and Biological Agency

Email: vaneeva.elena.vic@mail.ru

Russian Federation, Kirov, Russia

S V Samarina

Kirov Scientific Research Institute of Hematology and Blood Transfusion of the Federal Medical and Biological Agency

Email: vaneeva.elena.vic@mail.ru

Russian Federation, Kirov, Russia

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Supplementary files

Supplementary Files Action
1.
Рис. 1. Лимфатический узел. Иммуногистохимическая окраска опухолевых клеток антителом к pSTAT3: а — уровень ядерной экспрессии рSTAT3 ≥68%; б — уровень ядерной экспрессии рSTAT3 <68%, ×1000

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2.
Рис. 2. Лимфатический узел. Иммуногистохимическая окраска опухолевых клеток антителом к pАКТ1: а — уровень ядерной экспрессии pАКТ1 ≥70%; б — уровень ядерной экспрессии pАКТ1 <70%, ×1000

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3.
Рис. 3. Общая (а) и бессобытийная (б) выживаемость больных диффузной В-крупноклеточной лимфомой в зависимости от степени экспрессии рSTAT3

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4.
Рис. 4. Общая (а) и бессобытийная (б) выживаемость больных диффузной В-крупноклеточной лимфомой в зависимости от степени экспрессии рАКТ1

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5.
Рис. 5. Общая (а) и бессобытийная (б) выживаемость больных с различным сочетанием экспрессии рSTAT3 и рАКТ1

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© 2020 Vaneeva E.V., Rosin V.A., Dyakonov D.A., Samarina S.V.

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