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. 2022 Sep 12;12(1):15347.
doi: 10.1038/s41598-022-18894-2.

Salivary orosomucoid 1 as a biomarker of hepatitis B associated hepatocellular carcinoma

Jiaoxia He  1 , Zhongling Zheng  1 , Tingting Liu  1 , Yupei Ao  1 , Yixuan Yang  1 , Huaidong Hu  2
Affiliations

Salivary orosomucoid 1 as a biomarker of hepatitis B associated hepatocellular carcinoma

Jiaoxia He et al. Sci Rep. .

Abstract

Saliva is rich in proteins, DNA, RNA and microorganisms, and can be regarded as a biomarker library. In order to explore a noninvasive and simple means of early screening for liver cancer, proteomics was used to screen salivary markers of hepatitis B associated liver cancer. We used mass spectrometry coupled isobaric tags for relative and absolute quantitation (iTRAQ)-technology to identify differentially expressed proteins (DEPs). Western blot, immunohistochemistry and enzyme linked immunosorbent assay were used to detect marker expression of in tissues and saliva. Statistical analysis was used to analyze the diagnostic efficacy of the markers was analyzed through statistical analyses. By comparing the hepatocellular carcinoma (HCC) group with non-HCC groups, we screened out 152 salivary DEPs. We found orosomucoid 1(ORM1) had significantly higher expression in saliva of HCC patients compared with non-HCC groups (p < 0.001) and the expression of ORM1 in liver cancer tissues was significantly higher than that in adjacent normal tissues (p < 0.001). The combination of salivary ORM1 and alpha-fetoprotein (AFP) showed reasonable specificities and sensitivities for detecting HCC. In a word, salivary ORM1 as a new biomarker of hepatitis B associated hepatocellular carcinoma, combination of salivary ORM1 and AFP as an improved diagnostic tool for hepatocellular carcinoma.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Western blot verification. (a) Representative images of Western blot for AFP, HP, ORM1, ARG1, COTL1, FCG3B and MMP9 in HCC, LC, CHB and NC mixed saliva; Analysis of band densities by Image J. (b) Representative images of Western blot for AFP, HP, and ORM1 in 3 subjects' saliva from HCC, 3 subjects' saliva from LC, 3 subjects' saliva from CHB and 3 subjects' saliva from NC; Analysis of band densities by Image J. The samples derive from the same experiment and blots were processed in parallel. Original blots are presented in Supplementary Figure. HCC hepatocellular carcinoma, LC liver cirrhosis, CHB chronic viral hepatitis B, NC normal control, AFP α-fetoprotein, HP Haptoglobin, ORM1 Orosomucoid1, ARG1 Arginase-1, COTL1 Coactosin-like protein, FCGR3B Low affinity immunoglobulin gamma Fc region receptor III-B, MMP9 Matrix metalloproteinase-9. Data are shown as mean ± SD, *p < 0.05, versus liver cirrhosis, chronic viral hepatitis and normal control.
Figure 2
Figure 2
Immunohistochemistry verification. (a) Representative immunohistochemistry staining and analysis of differences in staining index of AFP in hepatocellular carcinoma tissue and tumor adjacent tissues. (b) Representative immunohistochemistry staining and analysis of differences in staining index of ORM1 in hepatocellular carcinoma tissue and tumor adjacent tissues. (c) Representative immunohistochemistry staining and analysis of differences in staining index of HP in hepatocellular carcinoma tissue and tumor adjacent tissues. AFP, ORM1 and HP are secreted proteins, localized in the cytoplasm and extracellular matrix. AFP α-fetoprotein, HP Haptoglobin, ORM1 Orosomucoid1. Data are shown as median with range, *p < 0.05, **p < 0.001.
Figure 3
Figure 3
Elisa verification. (a) Salivary AFP expression in total HCC, LC, CHB and NC groups. (b) Salivary ORM1 expression in total HCC, LC, CHB and NC groups. (c) Salivary HP expression in HCC, LC, CHB and NC groups. (d) Salivary AFP expression in early HCC, LC, CHB and NC groups. (e) Salivary ORM1 expression in early HCC, LC, CHB and NC groups. (f) Salivary HP expression in early HCC, LC, CHB and NC groups. AFP α-fetoprotein, HP Haptoglobin, ORM1 Orosomucoid1, HCC hepatocellular carcinoma, LC liver cirrhosis, CHB chronic viral hepatitis B, NC normal control. Data are shown as median with range.
Figure 4
Figure 4
Target proteins and prognosis of HCC. (a) Salivary ORM1 expression difference between early and late HCC. (b) Salivary AFP expression difference between early and late HCC. (c) Salivary ORM1 expression difference between HCC patients with the largest tumor diameter ≤ 3 cm and HCC patients with the largest tumor diameter > 3 cm. (d) Salivary AFP expression difference between HCC patients with the largest tumor diameter ≤ 3 cm and HCC patients with the largest tumor diameter > 3 cm. (e) Salivary ORM1 expression difference between HCC patients with and without metastasis. (f) Salivary AFP expression difference between HCC patients with and without metastasis. AFP α-fetoprotein, HP Haptoglobin, ORM1 Orosomucoid1, HCC hepatocellular carcinoma. Data are shown as median with range.
Figure 5
Figure 5
Correlation analysis of salivary AFP and serum AFP. AFP α-fetoprotein, HCC hepatocellular carcinoma, LC liver cirrhosis, CHB chronic viral hepatitis B.
Figure 6
Figure 6
ROC curves. (a) The ROC curves of serum AFP in diagnosis HCC. (b) The ROC curves of salivary AFP in diagnosis HCC. (c) The ROC curves of salivary ORM1 in diagnosis HCC. (d) The ROC curves of saliva ORM1 and saliva AFP combination in diagnosis HCC. AFP α-fetoprotein, ORM1 Orosomucoid1, HCC hepatocellular carcinoma, LC liver cirrhosis, CHB chronic viral hepatitis B, ROC Receiver operating characteristic.
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References

    1. Sung H, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021;71:209–249. doi: 10.3322/caac.21660. - DOI - PubMed
    1. Llovet JM, et al. Hepatocellular carcinoma. Nat. Rev. Dis. Primers. 2021;7:6. doi: 10.1038/s41572-020-00240-3. - DOI - PubMed
    1. McGlynn KA, Petrick JL, El-Serag HB. Epidemiology of hepatocellular carcinoma. Hepatol. (Baltimore Md.) 2021 doi: 10.1002/hep.31288. - DOI - PMC - PubMed
    1. Yang JD, Heimbach JK. New advances in the diagnosis and management of hepatocellular carcinoma. BMJ. 2020;371:m3544. doi: 10.1136/bmj.m3544. - DOI - PubMed
    1. Harris PS, et al. Hepatocellular carcinoma surveillance: An evidence-based approach. World J. Gastroenterol. 2019;25:1550–1559. doi: 10.3748/wjg.v25.i13.1550. - DOI - PMC - PubMed

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