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Global Translational Medicine                              Blood parameters for SCLC and AC relapse prognosis



            significant differences between patients with a high and   relative amount (percentage) of the CXCR1 receptor in
            low risk of relapse-free survival.                 lymphocytes; [CXCR2] – the relative amount (percentage)
              The results of the Cox proportional hazards model   of the CXCR2 receptor in monocytes; “Y” is the result of
            analysis confirm the relationship of all 3 parameters with   the regression equation.
            relapse-free survival in both the univariate and multivariate   According to the AUC expert scale, the prognostic
            models (P < 0.05, Table 4).                        model is classified as “very good” quality with an AUC
                                                                      14
              In  the  high-risk  group  of  AC  recurrence, only  the   of 0.831.  The optimal threshold value for distinguishing
            absolute values of the concentration of monocytes,   low- and high-risk groups for tumor recurrence is 0.417,
            eosinophilic leukocytes, the ratio between them, the   with a sensitivity of 84.9%, and specificity of 89.0% (Table 7).
            proportion of lymphocytes with the CXCR1 receptor and   Specifically, if the Y value is >0.417, the probability that
            the CYFRA 21-1 level were significantly higher than in   the patient has a high risk of tumor recurrence is 90.4%.
            the low-risk group (Table 5). The remaining parameters   Conversely, if the Y value is ≤0.417, the probability that the
            (SII, IPI, SIRI indices, HIF-1α, CXCL5, CXCL8, TuM2   patient has a low risk of tumor recurrence is 84.9%.
            PK, CXCR1, etc.) did not demonstrate any significant   The performance of the proposed regression model is
            differences between the high-  and low-risk groups of   demonstrated by the Kaplan-Meier  graph, which shows
            patients. Only these five parameters were included in the   relapse-free survival in patients with Stage III SCLC
            Cox proportional hazards models, where they were found   (Figure 2).
            to significantly affect patient survival (Table 6).
                                                                 The 1-year follow-up shows the distribution of high
              The results of ROC analysis show the prognostic   and low relapse-free survival of patients with Stage III
            characteristics of the selected indicators for the duration   SCLC according to the results of the regression equation
            of relapse-free survival in Stage III SCLC (Table 7). The   Y (Figure  2), which corresponds to TNM stratification
            proportion of blood lymphocytes expressing the CXCR1   (Figure 1B). By the end of the 1  year, the survival rate
                                                                                          st
            receptor demonstrated the highest prognostic efficiency   for the low-risk group was 74% according to TNM
            (76.7%). The prognostic efficiency was 71.2% and 74.0% for   stratification, and 76% according to the regression equation
            CXCR2-positive monocytes and CYFRA 21-1, respectively.   of blood parameters. For patients with a high risk, survival
            To improve the accuracy of the results, the values of these   after treatment was 47% and 45%, according to TNM
            parameters were subjected to logistic regression analysis.   stratification and regression equation of blood parameters,
            The resulting Equation I includes a combination of these   respectively. Besides, there is a clear difference between
            indicators. The prognostic accuracy for the calculated   high and low survival of patients based on the regression
            threshold value (> 0.417) was 87.7% (Table 7).     equation as early as the first month after the treatment, with
                         +
                exp( 5.315 0.116 *[CYFRA +  ]                  this difference increasing over time. In contrast, the curve
                    −
                1.901*[CXCR +            2])                   difference in high and low relapse-free survival based on
                           1] 0.279 *[CXCR
            Y =                                         (I)    TNM stratification becomes visible only two months after
               1 exp( 5.315 0.116 *[CYFRA ]                    the treatment.
                           +
                      −
                 +
                +  1.901*[CXCR +  1] 0.279 *[CXCR 2])            According to the results of ROC analysis for selected
                                                               parameters in Stage III AC, the highest specificity (84.4%)
              Logistic regression equation for predicting relapse-free   was found for the relative number of lymphocytes
            survival in patients with Stage III SCLC.          expressing the CXCR1, while its diagnostic sensitivity did
              Note: [CYFRA] – the concentration (ng/ml) of the   not exceed 66.2% (Table 8). The values of other selected
            CYFRA 21-1 antigen in the blood serum; [CXCR1] – the   indicators  showed  comparable  figures,  with  sensitivity
            Table 4. Cox proportional hazards models for SCLC patients
            Indicator                         Univariate model                       Multivariate model
                                    HR          95% CI        P‑value       HR           95% CI        P‑value
            CXCR1, lymphocytes, %   1.122     1.003 – 1.241    *0.007       1.091      1.001 – 1.181    *0.021
            CXCR2, monocytes, %     1.023     1.002 – 1.044    *0.023       1.013      1.001 – 1.025    *0.043
            CYFRA 21-1, ng/ml       1.102     1.009 – 1.195    *0.027       1.073      1.009 – 1.137    *0.022
            Note: *: P<0.05 indicates the value is statistically significant.
            Abbreviations: HR: Hazards ratio; 95% CI: 95% Confidence interval; CXCR1: C-X-C motif chemokine receptor 1; CXCR2: C-X-C motif chemokine
            receptor 2; CYFRA 21-1: Cytokeratin 19 fragment antigen 21-1.


            Volume 3 Issue 4 (2024)                         7                               doi: 10.36922/gtm.4865
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