MMSL 2023, 92(4):291-297 | DOI: 10.31482/mmsl.2022.046

LABORATORY DIAGNOSIS OF HEPATOCELLULAR CARCINOMA – CONVENTIONAL BIOMARKERS AND BLOOD PLASMA SPECTROSCOPYReview article

Petr Hříbek ORCID...1,2*, Lucie Habartová ORCID...3, Johana Klasová ORCID...1, Kristýna Kubíčková ORCID...1, Tomáš Kupsa ORCID...2, Tomáš Tůma ORCID...2, Vladimír Setnička ORCID...3, Petr Urbánek ORCID...1
1 Ústřední vojenská nemocnice – vojenská fakultní nemocnice Praha, Interní klinika 1. LF UK a ÚVN Praha, Česká republika
2 Fakulta vojenského zdravotnictví, Univerzita Obrany, Hradec Králové, Česká republika
3 Ústav analytické chemie, Vysoká škola chemicko-technologická v Praze, Česká republika

Hepatocelulární karcinom (HCC) je nejčastější primární zhoubný nádor jater, který se ve většině případů rozvíjí v terénu jaterní cirhózy různé etiologie. Jen časná stadia onemocnění jsou indikována k chirurgické, potenciálně kurativní léčbě. Jen přibližně třetina HCC je zachycena v časných stadiích. Screeningovým vyšetřením rizikových skupin pacientů je ultrasonografie jater (USG) v 6měsíčních intervalech. USG má vedle svých známých výhod i značné limitace. Senzitivita USG pro časná stadia HCC se pohybuje pouze okolo 60 %. Vzhledem k tomu a i proto, že se jedná o expert dependentní metodu, existuje naléhává potřeba objektivního biomarkeru HCC. Alfa-fetoprotein je obecně vnímán jako biomarker HCC, nicméně jeho senzitivita a specificita pro účely diagnostiky či dokonce screeningu je nedostatečná. Byly zkoumány i jiné další biomarkery s různými výsledky, ale žádný nedosáhl efektivity USG. Poměrně novým přístupem k této problematice je spektroskopie krevní plazmy, která prokázala svoji účinnost u různých onemocnění. Z pohledu HCC se spektroskopii krevní plazmy věnovalo jen málo studií. Autoři prezentují v přehledu i vlastní práci, kdy spektroskopie krevní plazmy dosáhla senzitivity a specificity v odlišení nemocných s jaterní cirhózou bez HCC a s ním 88 %, respektive 90 %. Přes veškeré snahy nebyl dosud dostatečně spolehlivý a validovaný biomarker HCC použitelný pro účely časné diagnostiky a screeningu identifikován.

Keywords: hepatocelulární karcinom; screening; jaterní cirhóza; biomarker; onkomarker; spektroskopie; alfa-fetoprotein

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver, which in most cases develops in the field of liver cirrhosis of various etiologies. Only the early stages of the disease are indicated for surgical, potentially curative treatment. Only about a third of cases of HCC are caught in the early stages. The screening examination of risk groups of patients is liver ultrasonography (USG) at 6-month intervals. Besides its well-known advantages, USG has significant limitations. The sensitivity of USG for the early stages of HCC is only around 60 %. Considering this and also because it is an expert-dependent method, there is an urgent need for an objective HCC biomarker. Alpha-fetoprotein is generally perceived as a biomarker of HCC, however, its sensitivity and specificity for diagnostic or even screening purposes are insufficient. Other biomarkers have been investigated with varying results, but none have reached the effectiveness of USG. A relatively new approach to this problem is blood plasma spectroscopy, which has proven its effectiveness in various diseases. From the perspective of HCC, few studies have focused on blood plasma spectroscopy. In the review, the authors also present their work, where blood plasma spectroscopy achieved a sensitivity and specificity of 88 % and 90 %, respectively, in differentiating patients with liver cirrhosis without and with HCC. Despite all efforts, a sufficiently reliable and validated biomarker of HCC usable for early diagnosis and screening has not yet been identified.

Keywords: Hepatocellular carcinoma; screening; liver cirrhosis; biomarker; oncomarker; spectroscopy; alpha-fetoprotein

Received: July 19, 2022; Revised: October 10, 2022; Accepted: October 11, 2022; Prepublished online: January 20, 2023; Published: December 1, 2023  Show citation

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Hříbek, P., Habartová, L., Klasová, J., Kubíčková, K., Kupsa, T., Tůma, T., Setnička, V., & Urbánek, P. (2023). LABORATORY DIAGNOSIS OF HEPATOCELLULAR CARCINOMA – CONVENTIONAL BIOMARKERS AND BLOOD PLASMA SPECTROSCOPY. MMSL, 92(4), 291-297. doi: 10.31482/mmsl.2022.046
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    References

    1. Sung H, Ferlay J, Siegel RL, 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(3):209-249. Go to original source... Go to PubMed...
    2. Dušek L. Epidemiologie zhoubných nádorů v České republice online: Masarykova univerzita; 2018 [2022-4-23]. Available from: http://www.svod.cz.
    3. Trinchet JC, Bourcier V, Chaffaut C, et al. Complications and competing risks of death in compensated viral cirrhosis (ANRS CO12 CirVir prospective cohort). Hepatology. 2015;62(3):737-750. Go to original source... Go to PubMed...
    4. Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19(3):329-338. Go to original source... Go to PubMed...
    5. El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365(12):1118-1127. Go to original source... Go to PubMed...
    6. Takayama T, Makuuchi M, Hirohashi S, et al. Early hepatocellular carcinoma as an entity with a high rate of surgical cure. Hepatology. 1998;28(5):1241-1246. Go to original source... Go to PubMed...
    7. Roayaie S, Blume IN, Thung SN, et al. A system of classifying microvascular invasion to predict outcome after resection in patients with hepatocellular carcinoma. Gastroenterology. 2009;137(3):850-855. Go to original source... Go to PubMed...
    8. Khalaf N, Ying J, Mittal S, et al. Natural History of Untreated Hepatocellular Carcinoma in a US Cohort and the Role of Cancer Surveillance. Clin Gastroenterol Hepatol. 2017;15(2):273-281 e1. Go to original source... Go to PubMed...
    9. Piscaglia F, Svegliati-Baroni G, Barchetti A, et al. Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: A multicenter prospective study. Hepatology. 2016;63(3):827-838. Go to original source... Go to PubMed...
    10. Heimbach JK, Kulik LM, Finn RS, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018;67(1):358-380. Go to original source... Go to PubMed...
    11. European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018;69(1):182-236. Go to original source... Go to PubMed...
    12. Singal A, Volk ML, Waljee A, et al. Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis. Aliment Pharmacol Ther. 2009;30(1):37-47. Go to original source... Go to PubMed...
    13. Masopust J, Kithier K, Radl J, et al. Occurrence of fetoprotein in patients with neoplasms and non-neoplastic diseases. Int J Cancer. 1968;3(3):364-373. Go to original source... Go to PubMed...
    14. Senturk H, Cumali R. Extreme elevation of serum alpha fetoprotein in decompensated cirrhosis without HCC: an ominous sign. Int J Biol Markers. 2007;22(1):19-23. Go to original source...
    15. Di Bisceglie AM, Sterling RK, Chung RT, et al. Serum alpha-fetoprotein levels in patients with advanced hepatitis C: results from the HALT-C Trial. J Hepatol. 2005;43(3):434-441. Go to original source... Go to PubMed...
    16. Trevisani F, D'Intino PE, Morselli-Labate AM, et al. Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status. J Hepatol. 2001;34(4):570-575. Go to original source... Go to PubMed...
    17. Kubíčková K, Hříbek P, Koula M, et al. Screening hepatocelulárního karcinomu a kvalita surveillance v reálné praxi. Farmakoterapie 2019;15(3):384-389.
    18. Bai DS, Zhang C, Chen P, et al. The prognostic correlation of AFP level at diagnosis with pathological grade, progression, and survival of patients with hepatocellular carcinoma. Sci Rep. 2017;7(1):12870. Go to original source... Go to PubMed...
    19. Duvoux C, Roudot-Thoraval F, Decaens T, et al. Liver transplantation for hepatocellular carcinoma: a model including alpha-fetoprotein improves the performance of Milan criteria. Gastroenterology. 2012;143(4):986-994 e3; quiz e14-5. Go to original source... Go to PubMed...
    20. Park SJ, Jang JY, Jeong SW, et al. Usefulness of AFP, AFP-L3, and PIVKA-II, and their combinations in diagnosing hepatocellular carcinoma. Medicine (Baltimore). 2017;96(11):e5811. Go to original source... Go to PubMed...
    21. Huang C, Sheng S, Sun X, et al. Lens culinaris agglutinin-reactive alpha-fetoprotein decline after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma predicts survival. Clin Chim Acta. 2014;431:232-238. Go to original source...
    22. Furie B, Furie BC. Molecular basis of vitamin K-dependent gamma-carboxylation. Blood. 1990;75(9):1753-1762. Go to original source...
    23. Lee W, Chung HJ, Kim S, et al. PIVKA-II is a candidate marker for monitoring the effects of the oral anticoagulant warfarin. Clin Biochem. 2010;43(13-14):1177-1179. Go to original source... Go to PubMed...
    24. Nakamura S, Nouso K, Sakaguchi K, et al. Sensitivity and specificity of des-gamma-carboxy prothrombin for diagnosis of patients with hepatocellular carcinomas varies according to tumor size. Am J Gastroenterol. 2006;101(9):2038-2043. Go to original source... Go to PubMed...
    25. Mitchell AL, Gajjar KB, Theophilou G, et al. Vibrational spectroscopy of biofluids for disease screening or diagnosis: translation from the laboratory to a clinical setting. J Biophotonics. 2014;7(3-4):153-165. Go to original source... Go to PubMed...
    26. Schipper HM, Kwok CS, Rosendahl SM, et al. Spectroscopy of human plasma for diagnosis of idiopathic Parkinson's disease. Biomark Med. 2008;2(3):229-238. Go to original source... Go to PubMed...
    27. Fournier F, Guo R, Gardner EM, et al. Biological and biomedical applications of two-dimensional vibrational spectroscopy: proteomics, imaging, and structural analysis. Acc Chem Res. 2009;42(9):1322-1331. Go to original source... Go to PubMed...
    28. Stovickova L, Tatarkovic M, Logerova H, et al. Identification of spectral biomarkers for type 1 diabetes mellitus using the combination of chiroptical and vibrational spectroscopy. Analyst. 2015;140(7):2266-2272. Go to original source... Go to PubMed...
    29. Habartova L, Bunganic B, Tatarkovic M, et al. Chiroptical spectroscopy and metabolomics for blood-based sensing of pancreatic cancer. Chirality. 2018;30(5):581-591. Go to original source... Go to PubMed...
    30. Tatarkovic M, Miskovicova M, Stovickova L, et al. The potential of chiroptical and vibrational spectroscopy of blood plasma for the discrimination between colon cancer patients and the control group. Analyst. 2015;140(7):2287-2293. Go to original source... Go to PubMed...
    31. Taleb I, Thiefin G, Gobinet C, et al. Diagnosis of hepatocellular carcinoma in cirrhotic patients: a proof-of-concept study using serum micro-Raman spectroscopy. Analyst. 2013;138(14):4006-4014. Go to original source... Go to PubMed...
    32. Zhang X, Thiefin G, Gobinet C, et al. Profiling serologic biomarkers in cirrhotic patients via high-throughput Fourier transform infrared spectroscopy: toward a new diagnostic tool of hepatocellular carcinoma. Transl Res. 2013;162(5):279-286. Go to original source... Go to PubMed...
    33. Hříbek P, Habartová L, Kubíčková K, et al. The potential of spectroscopy in the dia gnosis of hepatocellular carcinoma - a pilot study. Gastroent Hepatol. 2021;5(75):404-409. Go to original source...

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