Six autoantibodies as potential differential biomarkers of hepatocellular carcinoma vs. liver cirrhosis and chronic hepatitis: A prospective multi‑institutional study

Okada, Rei; Otsuka, Yuichiro; Yokosuka, Osamu; Kato, Naoya; Imazaki, Fumio; Hoshino, Isamu; Sugiura, Norío; Mizumoto, Hideaki; Azemoto, Ryousaku; Kato, Kazúo; Shimada, Hideaki

doi:10.3892/ol.2022.13487

Cited by 3 publications

(4 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The s-MK-positive group showed poor overall survival. An s-MK-positive rate was not associated with stage, and this tendency was similar to the pattern of serum autoantibodies, as previously reported (5,6). s-MK is induced not only by cancer but also by various factors such as inflammation and hemodynamics (21).…”

Section: Discussionsupporting

confidence: 88%

“…However, its diagnostic performance is unsatisfactory, with low sensitivity and specificity. To improve the diagnosis of HCC, advances in biomarker detection techniques have led to the identification of several new biomarkers, such as autoantibodies and s-MK (4)(5)(6). s-MK, an emerging serum biomarker, activates several cell surface receptors to modulate various biological activities and is significantly increased in HCC (7).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prognostic and diagnostic effects of high serum midkine levels in patients with hepatocellular carcinoma

Okada,

Otsuka,

Kajiwara

et al. 2024

Oncol Lett

Self Cite

View full text Add to dashboard Cite

Midkine (MK) is a soluble cytokine, and its serum levels strongly correspond to protein expression levels in tumors. The present study aimed to clarify the clinicopathological and prognostic significance of serum MK (s-MK) in patients with hepatocellular carcinoma (HCC). Serum samples were obtained before surgery from 123 patients with HCC who had undergone surgery between January 2012 and December 2020. The receiver operating characteristic curve revealed that the best cut-off value for s-MK in differentiating HCC from healthy cases was 426 pg/ml. The clinicopathological variables and overall survival of patients were compared between the s-MK-positive group and s-MK-negative group. The sensitivity, specificity and accuracy of s-MK were 82.1, 97.4 and 88.0%, respectively. An s-MK-positive status was significantly associated with the number of tumors (≥2). The positivity rate of s-MK was significantly higher compared with that of α-fetoprotein and protein-induced by vitamin K absence-II. In total, only 28% of the patients were positive for s-MK. The s-MK-positive group showed significantly worse overall survival compared with the s-MK-negative group. Moreover, multivariate analysis revealed that an s-MK-positive status was independently associated with poor prognosis. s-MK was useful in detecting early HCC. The findings of this study indicated that the s-MK-positive status is associated with the number of tumors and can act as an independent prognostic risk factor.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Prognostic and diagnostic effects of high serum midkine levels in patients with hepatocellular carcinoma

Okada,

Otsuka,

Kajiwara

et al. 2024

Oncol Lett

Self Cite

View full text Add to dashboard Cite

show abstract

“…One study with multiple TAAbs including anti-p16 in PC patents indicated that autoantibody to p16 showed the highest sensitivity (30.4%) in PC patients across 6 TAAbs ( P53, p16, p62, Survivin, IMP1) [16], in which, the performance of anti-p16 is similar to that in our current study. Anti-Sui1 is [23,9] the most frequently detected and evaluated autoantibody in HCC and Okada's study showed the highest sensitivity for the detection of HCC among six autoantibodies [21]. However, no report has been seen in PC, thus autoantibody to Sui1 is a newly discovered marker for the detection of PC.…”

Section: Discussionmentioning

confidence: 97%

“…In this study, autoantibodies to nine proteins TAAs including Guanine Nucleotide-Binding Protein Subunit Alpha-11 (GNA11), Mesothelin (MSLN), Guanine Nucleotide Binding Protein, Alpha Stimulating (GNAS), CCAAT/Enhancer-Binding Protein Alpha (CEBPA), Murine Double Minute 2 (MDM2), Cyclin-Dependent Kinase Inhibitor 2A (CDKN2A or P16), eukaryotic translation initiation factor 1 ( eIF1 or Sui1), nucleobindin (Calnuc), Phosphatase and Tensin homolog (PTEN) which were previously studied in other types of cancer [17][18][19][20][21][22] were detected by Enzyme-Linked Immunosorbent Assay (ELISA) in serum samples from pancreatic cancer patients and normal controls, as well as serum samples collected before and after chemotherapy, with the following objectives: (1) whether the autoantibodies corresponding to the nine target proteins have positive reactions in PC patients;…”

mentioning

confidence: 99%

Evaluation of multiple autoantibodies to tumor-associated antigens as potential diagnostic markers for pancreatic cancer

Wang,

Qiu,

Qin

et al. 2024

J Gastroenterol Res Pract

View full text Add to dashboard Cite

The aim of the study is to evaluate the clinical significance of autoantibodies to GNA11, MSLN, GNAS, CEBPA, MDM2, p16, Sui1, Calnuc, PTEN in Pancreatic Cancer (PC). A total of 33 sera from PC patients and 45 sera from Normal Controls (NC) were enrolled to measure nine autoantibodies by Enzyme-Linked Immunosorbent Assay (ELISA). Multiple parameters in individual or combination forms were applied for evaluation. The level of all autoantibodies except anti-GNAS and anti-Calnuc was significantly higher in PC patients than that in normal controls. Significantly increased frequencies were found for four autoantibodies to MSLN, p16, PTEN and Sui1 at 75.8%, 66.7%, 30.3% and 27.3% compared to normal controls (4.9%). The ability of these autoantibodies to distinguish PC patients from normal controls reflected by the area under ROC curve (AUC) ranged from 0.666 to 0.884, with anti-p16 (0.884 of AUC) and anti-MSLN (0.857 of AUC) showing the strongest diagnostic performance. The combination of anti-MSLN and anti-p16 could improve the diagnostic sensitivity. In addition, two autoantibodies to MSLN and Sui1 in PC patients decreased after chemotherapy. Four autoantibodies to MSLN, p16, Sui1, PTEN showed potential diagnostic markers for pancreatic cancer, with anti-MSLN and anti-p16 in best performance. The combination of these two autoantibodies showed the most economical and practical potential. The significance of the reduction of autoantibodies to MSLN and Sui1 in PC patients who were subjected to chemotherapy needs to be further explored.

show abstract

Prognostic and diagnostic effects of high serum midkine on patients with hepatocellular carcinoma

Okada,

Otsuka,

Kajiwara

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Background Midkine (MK) is a soluble cytokine, and its serum levels strongly correspond with protein expression levels in tumors. This study aimed to clarify the clinicopathological and prognostic significance of serum MK (s-MK) in patients with hepatocellular carcinoma (HCC).Methods Serum samples were obtained before surgery from 123 patients with HCC who underwent surgery between 2012 and 2020. Based on the receiver operating characteristics curve, the best cutoff value for s-MK in differentiating HCC from healthy cases was 426 pg/mL. Patients’ clinicopathological variables and overall survival were compared between the s-MK-positive group and the s-MK-negative group.Results The sensitivity, specificity, and accuracy of s-MK were 82.1%, 97.4%, and 88.0%, respectively. An s-MK-positive status was significantly associated with the number of tumors (≥ 2). The positivity rate of s-MK was significantly higher than that of α-fetoprotein and protein induced by vitamin K absence-II. In total, only 28% of the patients were positive for s-MK. The s-MK positive group showed significantly worse overall survival than the s-MK negative group. The multivariate analysis revealed that an s-MK-positive status was independently associated with poor prognosis.Conclusion s-MK was useful in detecting early HCC. A s-MK-positive status was associated with the number of tumors and was an independent prognostic risk factor.

show abstract

Six autoantibodies as potential differential biomarkers of hepatocellular carcinoma vs. liver cirrhosis and chronic hepatitis: A prospective multi‑institutional study

Abstract: Serum autoantibodies respond not only to tumor-associated antigens of hepatocellular carcinoma (HCC) but also to those of liver cirrhosis (LC) and chronic hepatitis (CH).

Cited by 3 publications

References 35 publications

Prognostic and diagnostic effects of high serum midkine levels in patients with hepatocellular carcinoma

Prognostic and diagnostic effects of high serum midkine levels in patients with hepatocellular carcinoma

Evaluation of multiple autoantibodies to tumor-associated antigens as potential diagnostic markers for pancreatic cancer

Prognostic and diagnostic effects of high serum midkine on patients with hepatocellular carcinoma

Contact Info

Product

Resources

About