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Global Translational Medicine                              Blood parameters for SCLC and AC relapse prognosis



            risk of relapse. It has been previously shown that cellular   of monocytes (64.9%), and the highest for lymphocytes
            ratios such as N/L, P/L, and L/M, as well as the level of CRP,   expressing CXCR1 receptor (75.3%).
            were known as indicators of the inflammatory reaction   Three parameters in patients with SCLC (proportions of
            associated with tumor development.  At the same time,   lymphocytes expressing the CXCR1 receptor, monocytes
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            elevated levels of CRP, N/L, and P/L ratios, along with a   expressing the CXCR2 receptor, and CYFRA 21-1 level) and
            decreased L/M ratio, have been associated with a poor   three parameters in patients with AC (CYFRA 21-1 level,
            prognosis in NSCLC. The prognostic value of the N/L ratio   lymphocytes expressing the CXCR1 receptor, and the E/M
            was higher compared to P/L ratio.  Conversely, findings   ratio) were included in the regression analysis to construct
                                        16
            from other studies suggest that the prognosis of NSCLC   the  equation.  The  resulting  equations  were  expected  to
            is associated with the cellular ratio of P/L rather than the   exhibit higher sensitivity and specificity in stratifying
            N/L ratio. 17,18  Similar inconsistency of results has also been   patients with Stage III AC based on the duration of relapse-
            found in the assessment of the prognostic value of CRP. 19  free survival. Utilizing a combination of parameters or
              The findings of our investigation demonstrated that   markers is a common technique for improving prognostic
            in Stage III SCLC, only the proportion of lymphocytes   accuracy. 25-30  The convenience of the regression equation
            expressing  the  CXCR1  receptor,  monocytes  expressing   lies in its ability to combine several markers into a single
            the CXCR2 receptor, and the CYFRA 21-1 level showed   numerical value, streamlining prognostic analysis.
            significant differences between patients with high and low   All the prognostic characteristics (sensitivity, specificity
            risk of relapse-free survival. For the high-risk group of   etc.) were much higher than when using each indicator
            AC recurrence, the absolute concentrations of monocytes,   separately for a similar prognostic purpose. For Stage III
            eosinophilic  leukocytes,  eosinophilic-to-monocyte  ratio,   SCLC, the prognostic accuracy in predicting relapse-free
            the  proportion  of lymphocytes  expressing  the CXCR1   survival (Y > 0.417) was 87.7%.
            receptor,  and  the  CYFRA  21-1  level,  are  significantly
            higher than in the low-risk group. In contrast, other   For patients with Stage III AC, the optimal threshold
            parameters, including SII, IPI, and SIRI indices, the levels   value for distinguishing between low- and high-risk groups
            of HIF-1α, CXCL5, CXCL8, TuM2 PK, and CXCR1,       of tumor recurrence was 0.597. Specifically, if the value of
            did not demonstrate significant differences between the   Z > 0.597, the patient has an 89.6% probability of high
            high- and low-risk groups of patients.             tumor recurrence, while for value of Z ≤ 0.597, 84.4% of
                                                               patients are correctly predicted to have a low risk of tumor
              Therefore, only different parameters were used in the   recurrence. The use of the logistic equation significantly
            Cox proportional hazards models, which show their equal   improved the probability in accurately predicting a low or
            significance for patient survival. Besides, the results of the   high risk of tumor recurrence, reaching an overall accuracy
            multivariate analysis confirmed the results of the univariate   of 89.0% (with sensitivity of 85.7%, and specificity of 94.8%).
            analysis, establishing a connection between the selected   As illustrated, all these indicators were notably higher than
            set of parameters and relapse-free survival. This approach   those achieved when using individual parameters for the
            validated the identification of the selected parameters   same prognostic purpose.
            as prognostic markers and assessed their influence on   The distribution of relapse-free survival into relatively
            prognosis in terms of odds ratios.
                                                               high and low, according to the results of logistic equation,
              However, the generally accepted criteria for the   aligns to the results of TNM stratification. In patients with
            diagnostic and prognostic value of a specific marker   Stage III SCLC, the relapse-free survival at the end of the
            include threshold value, diagnostic sensitivity, specificity,   first year for those at low risk of tumor recurrence is 79%
            efficiency, etc.  The results of the ROC analysis for the   according to TNM stratification and 77% when selected
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            selected indicators showed that the proportion of blood   blood parameters are included in the regression equation.
            lymphocytes expressing the CXCR1 receptor demonstrated   For patients with a high risk of tumor recurrence, survival
            the highest prognostic efficiency (75.3%) for predicting   at the end of the 1  year after treatment is 49% and 48%,
                                                                              st
            relapse-free survival in patients with stage III SCLC. For   respectively. Another notable observation is that a clear
            Stage III AC, the highest specificity (84.4%) was observed   difference between the high and low survival curves
            for the relative proportion of lymphocytes expressing the   occurs as early as the 1  month after the treatment, with
                                                                                  st
            CXCR1, while the diagnostic sensitivity of this indicator   this difference subsequently increasing. In contrast, the
            did  not  exceed  66.2%.  The  diagnostic  sensitivity  values   differences in the high and low relapse-free survival curves
            of other selected indicators were in the range of 62.3% to   constructed based on TNM appear only two months after
            76.6%. As a result, the diagnostic efficiency in predicting   the treatment. In subsequent studies, further verification
            relapse-free survival was the lowest for the concentration   of the proposed prognostic model is needed, not only to


            Volume 3 Issue 4 (2024)                         11                              doi: 10.36922/gtm.4865
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