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Gene & Protein in Disease                                       PIVKA-II in differential diagnosis of AFP-NHCC



            of HCC can provide the opportunity for timely treatment,   very early-, early-, and even middle-stage liver cancer is
            thereby improving the survival rate of patients. Therefore,   not high in China, and the reasons are as follows 26-28 ;  the
            the clinical consensus is that very early intervention is the   pre-cancerous lesion of HCC, in which a nodule is formed
            best treatment strategy.  However, the diagnosis rate of   from the proliferation of a single hepatocyte clone has
                               25
                                                               abnormal cytology and histology, but does not meet HCC
                                                               criteria; HCC is divided into low- and high DNA, there is
                                                               no clear distinction between atypical hyperplastic nodules
                                                               DNA and HCC. Although MRI and other high-resolution
                                                               examination methods can increase the detection probability
                                                               of small lesions, these techniques are not feasible during
                                                               the 1 -time screening due to high cost and other inherent
                                                                   st
                                                               problems. The early-stage condition of certain patients
                                                               lacks specificity and also demonstrates low awareness of
                                                               the need for active examination. The diagnostic efficacy
                                                               of AFP cannot meet the actual needs of clinical practice,
                                                               and there is a greater possibility of false positive and false
                                                               negative results which ultimately lead to the progress
                                                               of liver cancer patients in the middle and late stage or
            Figure 1. Diagnostic ROC curve of PA, PIVKA-II, and all inflammatory   terminal stage at the time of diagnosis, which is extremely
            indexes for AFP-NHCC                               unfavorable to their treatment and quality of life. With
            Abbreviations: AFP-NHCC: Alpha-fetoprotein-negative hepatocellular
            carcinoma; PA: Prealbumin; ROC: Receiver operating characteristics.  the progress of medical technology and human society,
                                                               laboratory examination of tumor markers supported by
                                                               bioinformatics technology has become a global research
                                                               hotspot on the grounds of their minimal invasiveness and
                                                               the reproducibility nature of results. The occurrence and
                                                               development process of most tumors shares very similar
                                                               characteristics,  and more and more studies have been
                                                                           29
                                                               conducted regarding the impact of chronic inflammation
                                                               on the occurrence and development of tumors. Due to
                                                               the low effectiveness and prolonged time required in the
                                                               detection methods employing most inflammatory indexes,
                                                               many researchers have become more interested in using
                                                               tumor markers and inflammatory indicators with high
                                                               specificity, high accuracy, and high sensitivity for tumor
                                                               screening and diagnosis.
                                                                 As can be seen from Table 1, the hs-CRP, PA, NLR, and
            Figure 2. Diagnostic ROC curve of hs-CRP, NLR, and PIVKA-II for AFP-  PIVKA-II of patients in the benign lesion group and the
            NHCC                                               AFP-NHCC group were higher than those in the healthy
            Abbreviations: AFP-NHCC: Alpha-fetoprotein-negative hepatocellular
            carcinoma; hs-CRP: High-sensitivity C-reactive protein; NLR:   control group, and the levels of the  above indicators in
            Neutrophil-lymphocyte ratio; ROC: Receiver operating characteristics.  the AFP-NHCC group were also higher than those in the

            Table 3: Performance analysis of different diagnostic methods

            Diagnostic mode          AUC    Standard   P    95% confidence   Sensitivity  Specificity  Youden   Cut‑off
                                             error             interval                        index    value
            PIVKA-II                 0.858   0.037   <0.001  0.786 – 0.930  84.40     73.80     0.582   602.16
            hs-CRP                   0.843   0.046   <0.001  0.754 – 0.933  56.78     68.87     0.61    59.06
            PA                       0.671   0.059    0.007  0.557 – 0.786  78.10     56.90     0.35    53.57
            NLR                      0.736   0.053   <0.001  0.632 – 0.840  75.00     72.80     0.478    1.36
            PIVKA-II + inflammatory indexes  0.895  0.036  <0.001  0.825 – 0.965  84.40  82.80  0.672     -
            Abbreviations: AUC: Area under the curve; hs-CRP: High-sensitivity C-reactive protein; NLR: Neutrophil-lymphocyte ratio; PA: Prealbumin.


            Volume 3 Issue 4 (2024)                         5                               doi: 10.36922/gpd.4269
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