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

benign lesion group. This is in line with the conclusion that accelerate the proliferation rate and colonization ability
it is difficult to detect the abnormal substances encoded of tumor cells and assist tumor cells in immune escape.
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by oncogenes, tumor suppressor genes, and other tumor- In addition, tumor cells can upregulate the levels of
related genes in normal tissues and benign lesions. 30,31 The CXCL12 and other substances in bone marrow stromal
mechanism of tumorigenesis is complex. The discovery cells, and promote the increase of neutrophil levels. After
of a large number of white blood cells in tumor tissues in the occurrence of the tumor, the expression levels of
1863 has driven more people to be acquainted with the serum IL-6, IL-2, tumor necrosis factor, and other factor
idea that the chronic and persistent inflammatory reaction receptors are increased under normal circumstances, and
in tumor tissues or their surrounding tissues, resulting the number of lymphocytes is correspondingly decreased,
in local lymphocyte infiltration, is the root cause of thereby inhibiting tumor proliferation and migration. 46
tumorigenesis. 32,33 According to studies, 20% of malignant The increase of neutrophil count and/or the decrease
tumors are mainly caused by inflammation, and its related of lymphocyte number can lead to the increase of
mechanism is not yet clear. The possible reason is that the
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contents of active oxides and active nitrides produced by NLR, and the change of NLR can indicate the severity
the inflammatory cells increase following the proliferation of inflammation and the strength of immunity and
of a large number of cells. Inhibition of the antioxidant indirectly reflect the balance between the tumor-
defense system results in excessive oxidative stress, and promoting environment and anti-tumor state of the
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the overload of active substances can damage the stability body. Studies have shown that: (i) the vast majority
of DNA. Eventually, gene deletion and point mutation of tumor patients undergoing chemotherapy or surgical
occur. 35-37 resection would not undergo NLR progression for a long
period of time; (ii) the rapid increase of NLR indicates
Although the cause of HCC is unknown, it is the potential occurrence of tumor growth or metastasis;
generally believed that the occurrence of liver cancer is (iii) NLR reflects an immune microenvironment that is
basically the same as the process of hepatitis, cirrhosis, conducive to tumor vascular invasion and inhibitory to
and cancerization, so HCC is perceived as a tumor host immune surveillance. A high NLR is associated with
originating from inflammation. There have been studies a poor prognosis after transplantation. hs-CRP is widely
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reporting that SIR is closely related to the prognosis of used in clinical inflammation assessment. Synthesized
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liver cancer. Most HCCs are associated with chronic in the liver, hs-CRP is significantly increased in level
hepatitis B or C virus infection, and the host produces after inflammation. Another study also found that CRP
persistent chronic inflammation. The systemic and local levels were significantly elevated in HCC patients with
inflammatory responses of the virus or tumor can provide negative AFP and low AFP levels (<100 µg/mL). The
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a favorable microenvironment for tumor invasion and ROC curve of this paper shows that hs-CRP alone in
metastasis. 39,40 Chronic inflammation is even considered the diagnosis of AFP-NHCC has low sensitivity and
an important prognostic factor for HCC in the early specificity, which is unsuitable for clinical application.
stages of cancer progression. A large number of studies PA is also synthesized in the liver, and its half-life is
on advanced HCC have also shown that tumor-related relatively short. The application value of PA is discounted
inflammatory responses are associated with worse in the events of inflammation, trauma, malnutrition, or
pathological staging and clinical prognosis. 41,42 Simple liver disease. Some literature pointed out that PA can
inflammation-related indices derived from laboratory predict the overall survival and relapse-free survival of
tests have been found to have predictive value for the liver cancer patients, and some scholars 50,51 confirmed
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prognosis of liver transplantation in HCC patients. Our that PA is significantly correlated with CD8 , CD4 , and
43
+
+
study of inflammation markers hs-CRP, PA, and NLR, natural killer cells. It can predict the immune status of
which are elevated in AFP-HCC, confirms this. Under the patients with primary liver cancer well. In this study,
action of various exogenous and endogenous pathways, the diagnostic sensitivity of PA was acceptable, but the
signal transduction and transcription activator 3, nuclear specificity was very low.
transcription factor-KB, and other signaling pathways are
activated, resulting in the production of prostaglandins, PIVKA-II, also known as abnormal prothrombin
leukotrienes, nitric oxide, bradykinin, and other and des-γ-carboxy-prothrombin, is a liver-synthesized
inflammatory mediators. Recruitment of neutrophils, protein that is induced during Vitamin K deficiency, is
lymphocytes, and macrophages not only increases local caused by the incomplete carboxylation of the N-terminal
inflammation but also promotes neovascularization of the chemical chain of prothrombin due to Vitamin K
and inhibits the immune response to tumor tissues. In deficiency, resulting in the loss of the ability of prothrombin
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addition, neutrophils can release specific chemokines to to combine with other factors. In HCC patients, Vitamin K

Volume 3 Issue 4 (2024) 6 doi: 10.36922/gpd.4269