Predicting the risk of tumor progression in patients with early stages of adenocarcinoma and squamous cell lung carcinoma based on laboratory parameters

Abstract

Non-small cell carcinoma (NSCLC) prevails in the structure of the incidence of lung cancer. In patients with I stage NSCLC, only 60-70% overcome the 5-year survival barrier, and at II stage it decreases to 35-40%. The reason for such a high mortality rate is almost always a relapse of the disease. The main histological forms of NSCLC — adenocarcinoma (AC) and squamous cell carcinoma (SCLC) — differ in the course, protocols and effectiveness of the treatment. Comparative survival data for AK and PCLC are controversial, and reliable biomarkers for determining the risk of tumor progression are lacking. In thus study we have investigated the possibility of using laboratory parameters characterizing the level of some blood proteins involved in carcinogenesis in patients with early stages of AC and SCLC to determine the risk of disease progression. We retrospectively analyzed the duration of the relapse-free period after surgical treatment for one year in 1250 patients (816 with stages I and II of adenocarcinoma, G1-3 and 434 with early stages of SCLC, G1-3). In 81 patients with AC and 36 — with SCLC (stages I-II, G1-3) the level of CYFRA 21-1 and SCC by electrochemiluminescent method, chemokines CXCL5, CXCL8, TPA, pyruvate kinase M2, HIF-1α and hyaluronic acid by enzyme immunoassay, receptors CXCR1, CXCR2, CD44v6 by flow cytometry were determined. Using the Kaplan-Meier graphical analysis, groups of low (stage I G1-2 + stage II G1) and high (stage I G3 + stage II G2-3) risk of tumor progression were identified. In the case of the one-year survival rate of patients with AC was higher than with SCLC. In patients with AC and a high risk of tumor recurrence, compared with a low one, the level of CYFRA 21-1, the mean intensity of fluorescence (MFI) of the CXCR1 receptor in granulocytes, and the relative content of the CXCR2 receptor in lymphocytes were higher. In the case of rapid progression of SCLC in patients, the relative content of the CXCR2 receptor in lymphocytes, the proportion of monocytes equipped with the CD44v6 receptor, and the SCC level were higher than with slow progression. Regression equations, including combinations of the above parameters (threshold value for AC — 0,512, for SCLC — 0,409, sensitivity — 91,9% and 90,0%, specificity — 90,0% and 87,5%, respectively), allow to predict the probability of tumor recurrence.

Significance of CYFRA 21-1, CXCR1 and CXCR2 Receptors Blood Levels Determination in Predicting Lung Adenocarcinoma (Stages I–II) Recurrence

“…Комбинированная модель включала в себя результат регрессионного уравнения (Y) определения трех показателей: Х1 -концентрации антигена CYFRA 21-1 в сыворотке крови; Х2 -интенсивности флуоресценции рецептора CXCR1 в гранулоцитах (CXCR1, MFI, гранулоциты); X3 -относительного количества рецептора CXCR2 в лимфоцитах (CXCR2, %, лимфоциты) [11]: Для выяснения зависимости длительности безрецидивного периода от времени наблюдения строили графики Каплана -Майера. Сравнение групп пациентов с различной безрецидивной выживаемостью проводили, используя Log Rank тест и χ 2 (хи-квадрат).…”

“…РЕЗУЛЬТАТЫ И ОБСУЖДЕНИЕ В большей части случаев через 3 недели после хирургического удаления опухоли (19 из 28 пациентов) уровень CYFRA 21-1, CXCR1, MFI, гранулоциты, CXCR2, %, лимфоциты, комбинированной модели уменьшается до нормальных величин. У остальных 9 обследованных пациентов уровень этих показателей через 3 недели после оперативного лечения снизился по сравнению с их уровнем до операции, но по-прежнему превышал пороговые значения, рассчитанные нами ранее [11]. Из этих 9 пациентов у 5 в течение года развился рецидив опухоли, диагностированный по результатам КТ.…”

“…Проведенные нами ранее исследования позволили предложить 3 показателя в крови, дооперационный уровень которых дал возможность прогнозировать высокую или низкую безрецидивную выживаемость пациентов с немелкоклеточным раком легкого [11]. В их число вошли фрагмент 19 цитокератина CYFRA 21-1, плотность расположения рецептора CXCR1 на гранулоцитах (CXCR1, MFI, гранулоциты) и доля лимфоцитов в общей популяции этих клеток в крови, снабженных рецептором CXCR2 (CXCR2, %, лимфоциты).…”

Combined Determination of CYFRA 21-1 and CXCR1/2 Levels for Detecting Recurrence in Stage III Squamous Cell Lung Carcinoma

“…These results indicated the usefulness of the combined model in stage I-II SCLC patients as an additional marker for predicting postoperative relapse. 16,17 Thus, surgical treatment of stage III SCLC is associated with chemotherapy. Despite these efforts, some patients develop tumor relapses, mostly within the first year after surgery, which are associated with high mortality.…”

MCM4 acts as a biomarker for LUAD prognosis

“…It consists of two main subtypes, including small cell lung cancer (SCLC) and non‐SCLC (NSCLC) 3 . The latter is the common form of lung cancers, making up approximately 85%, and it is further classified into three types: lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC) and large cell carcinoma histologic subtypes 4–6 . LUAD develops from type II alveolar epithelial cells, 7–9 and constitutes unique lung cancer subtypes with mutational landscapes and distinct cellular 8 .…”