The level of serum soluble E-cadherin as an indicator of prognosis in patients with aggressive B-cell lymphomas



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Abstract

Introduction. Criteria for the effectiveness of therapy and the prognosis of disease development remain an urgent problem in oncology. The study of prognostic markers in blood serum is a promising way to track the dynamics of B—cell lymphomas during therapy..

Aim. To analyze the relationship between the presence of a tumor process and the level of the marker E-cadherin.

Materials and Methods. The study included 53 patients (30 men, 23 women) with B-cell lymphomas (stage 1 — 1 patient, stage 2A/2B — 9, 3A/3B — 9, 4A/4B — 34 patients). The level of soluble E-cadherin (sEcad) was determined before the start of treatment, after the third and sixth courses of CT. The dynamics of sEcad levels were performed both in the general group of patients and separately in subgroups of patients without and with recurrent lymphomas. The subgroups were comparable in age and stages of the disease. The control group consisted of 25 people (18 men, 7 women) without oncological pathology. The average age in the study and control groups was 61.2±2.1 (95% CI 57.1–65.3) versus 60.0±2.6 years (95% CI 49.7–60.3), p=0.08. As a normal value (in patients without tumor disease), we assumed a sEcad level of 1.0 ng/ml..

Results. Lymphoma recurrence was observed in 22 (42%) of 53 patients. Seven (13%) patients died of other non-tumor related causes, 1 (2%) patient lost to follow-up. E-cadherin level in the general group before the start of treatment was 3.7 ± 0.4 ng/ml, compared with 0.9 ± 0.1 ng/ml in the control group, p <0.0001. During the therapy, a decrease in the level of E-cadherin was observed after the third and sixth courses of CT to 2.8 ± 0.3 ng/ml and 2.4 ± 0.4 ng/ml, respectively. In the subgroups without relapse (n = 31) and with relapse of lymphomas (n = 22), serum E-cadherin levels before therapy, after three and six courses of chemotherapy were 3.5 ± 0.4, 2.4 ± 0.3 and 1.5 ± 0.2 ng/ml versus 4.1 ± 0.9, 3.4 ± 0.5 and 3.5 ± 0.7 ng/ml, p = 0.5, p = 0.1 and p = 0.003, respectively. Serum E-cadherin level in patients without relapse significantly decreased after 6 courses of CT compared to the time of diagnosis (p = 0.0001). Relapse-free survival (RFS) in the overall patient group was 50.3 ± 8%, with a median follow-up of 43.9 ± 5.2 months. RFS at E-cadherin levels ≤ 1.0 ng/mL and> 1.0 ng/mL after six courses of chemotherapy was 58.3 ± 16% versus 43.3 ± 11% with a mean follow-up of 46.4 ± 10.3 months versus 28.2 ± 4.1 months, respectively (p = 0.045).

Conclusions. The risk of B-lymphoma recurrence is lower at sEcad <1.0 ng/ml after six courses of therapy than at higher values of this marker. A decrease in this marker during treatment indicates a good response to therapy. For further research, it is necessary to expand the observation groups and standardize methods for determining the sEcad level.

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Табл. 1. Клинико-демографическая характеристика исследуемой группы пациентов

Table 1. Clinical and demographic characteristics of patients

Показатель

Значение

Возраст, (M±SD), лет

61,2±2,1

Пол, (n, %)

 

Мужской

30 (57%)

Женский

23 (43%)

Нозология, МКБ-10, (n, %):

 

С83.3 — Диффузная крупноклеточная В-клеточная лимфома (ДВКЛ)

51 (96%)

C85.2 — Медиастинальная (тимусная) большая В-клеточная лимфома (ПМВКЛ)

1 (2%)

С83.7 — Лимфома Беркитта (ЛБ)

1 (2%)

Стадия лимфомы, Ann-Arbor, (n, %):

 

1 стадия

1 (2%)

2А/2В стадия

9 (17%)

3А/3В стадия

9 (17%)

4А/4В стадия

34 (64%)

 

Табл. 2. Патологические события в исследуемой группе пациентов с В-клеточными лимфомами высокой степени злокачественности, в том числе в зависимости от наличия или отсутствия рецидива

Table 2. Pathological events in the study group of patients with high-grade B-cell lymphomas, depending on the presence or absence of relapse

Группы/Статус

Умерло (n, %)/Живы (n, %)

Рецидив

Смерть от других причин

Потеря из наблюдения

Общая

30 (57%)/23 (43%)

22

7

1

Группа без рецидива

8 (26%)/23 (43%)

0

7**

1

Группа с рецидивом

22 (100%)/–

22*

Примечания. * — 1 больной умер от ОНМК на фоне рецидива; ** — Covid-19 — 4, инфаркт — 1, ОНМК — 1, аспирационная пневмония — 1.

Табл. 3. Уровень сывороточного растворимого Е-кадгерина (sEcad ) в динамике, (M±SD, 95% доверительный интервал, нг/мл)

Table 3. Dynamics of serum soluble E-cadherin (sEcad) level (M±SD, 95% confidence interval, ng/mL)

Группа / Статус

До начала терапии Уровень sEcad

После 3 курсов ХТ Уровень sEcad

После 6 курсов ХТ Уровень sEcad

р

Контрольная группа (n=25)

0,9±0,1 (95% ДИ 0,8-1,0)

<0,0001*

Исследуемая (n=53)

3,7±0,4 (95% ДИ 2,9–4,5)

2,8±0,3 (95% ДИ 2,7–3,4)

2,4±0,4 (95% ДИ 1,7–3,1)

0,03**

Без рецидива (n=31)

3,5±0,4 (95% ДИ 2,6–4,3)

2,4±0,3 (95% ДИ 1,8–3,1)

1,5±0,2 (95% ДИ 1,1–1,9)

0,003***

Рецидив (n=22)

4,1±0,9 (95% ДИ 2,3–5,9)

3,4±0,5 (95% ДИ 2,3–4,4)

3,5±0,7 (95% ДИ 2,1–4,9)

Примечания. *— между группами исследуемой и контрольной; **— между уровнями до начала терапии и после 6 курсов ХТ; *** — между уровнями после 6 курсов ХТ в подгруппа с и без рецидива.

 

Рис. 1. Динамика уровней растворимого Е-кадгерина (sEcad) в сыворотке в общей группе (: ХТ — химиотерапия.

 

Рис. 2. Динамика уровней растворимого Е-кадгерина (sEcad) в сыворотке в подгруппе пациентов без рецидива (n=31) до химиотерапии на момент диагностики лимфомы, после 3 курсов химиотерапии и после 6 курсов химиотерапии): ХТ — химиотерапия.

 

Рис. 3. Зависимость безрецидивной выживаемости от уровня растворимого Е-кадгерина (sEcad) после шести курсов химиотерапии: cплошная линия — безрецидивная выживаемость пациентов с уровнем растворимого Е-кадгерина (sEcad) ≤1,0 нг/мл; пунктирная линия — безрецидивная выживаемость пациентов с уровнем сывороточного Е-кадгерина >1,0 нг/мл.

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About the authors

Andrey S. Komarov

Tver Regional Clinical Oncology Dispensary, Tver; Tver State Medical University, Tver

Email: andrey_komarow@inbox.ru
Russian Federation, Tver, Russia; Tver, Russia

Valeriya G. Shestakova

Tver State Medical University, Tver

Email: shestvg@mail.ru
ORCID iD: 0000-0003-1136-7396
SPIN-code: 4541-8220

MD, Dr. Sci. (Medicine), Assistant Professor

Russian Federation, Tver, Russia

Igor S. Dolgopolov

Neurovita Clinical Hospital, Moscow; Russian State Social University, Moscow

Email: irdolgopolov@gmail.com
ORCID iD: 0000-0001-9777-1220
SPIN-code: 4312-9786

MD, Dr. Sci. (Medicine)

Russian Federation, Moscow, Russia; Moscow, Russia

Nikolai N. Slyusar

Tver State Medical University, Tver

Email: slusar2011@rambler.ru
ORCID iD: 0000-0001-7865-0984

MD, Cand. Sci. (Medicine)

Russian Federation, Tver, Russia

Elena A. Chernyayeva

Tver State Medical University, Tver

Email: martus12345@yandex.ru
ORCID iD: 0009-0004-5106-9582
Russian Federation, Tver, Russia

Maxim Yu. Rykov

Russian State Social University, Moscow

Author for correspondence.
Email: wordex2006@rambler.ru
ORCID iD: 0000-0002-8398-7001
SPIN-code: 7652-0122

MD, Dr. Sci. (Medicine), Assistant Professor, Head of the Department of Pediatrics

Russian Federation, Moscow, Russia

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