The Predictive Value of CA-125 and Hb for Ocular Metastasis in Hepatocellular Carcinoma Patients

Figures & data

Table 1 The Clinical Characteristics of HCC Patients

Patient Characteristics	OM Group (n=20)	NOM Group (n=1044)	P value
Gender
Male	17(85.0)	950(90.9)	0.354
Female	3(15.0)	94(9.001)
Age, years
Mean	51.78±13.95	51.92±13.65	0.697

Notes: Chi-squared test and Student’s t-test were used. P < 0.05 indicated statistical significance.

Abbreviations: OM, ocular metastasis; NOM, non-ocular metastasis; HCC, hepatocellular carcinoma.

Figure 1 The demographic characteristics of the included cases (A and B) and different types of cancer with ocular metastases (C).

Table 2 Differences in Tumor Markers Between HCC Patients with and without OM

Tumor Markers	OM Group	NOM Group	t	P value
CEA (ng/mL)	11.29±26.81	518.46±12,112.28	1.426	0.941
CA-125 (u/mL)	499.41±356.26	116.43±244.63	15.975	<0.001
CA-199 (u/mL)	191.34±300.31	214.96±3879.47	1.839	0.840
CA-153 (u/mL)	18.47±13.04	19.29±21.08	27.832	0.510
CA-724 (u/mL)	7.81±9.30	6.74±5.52	33.569	0.332
FER (mmol/L)	230.84±248.97	250.37±177.25	45.386	0.836
ALP (mmol/L)	207.5±90.88	149.73±131.45	36.439	0.394
TG (mmol/L)	4.74±1.85	6.05±12.76	13.376	0.754
TC (mmol/L)	1.88±1.38	1.40±1.07	12.530	0.477
HDL (mmol/L)	1.57±1.30	1.47±1.04	15.051	0.320
LDL (mmol/L)	2.91±1.97	2.50±1.28	37.552	0.481
ApoA (g/L)	1.64±0.47	1.54±0.42	40.284	0.519
ApoB (g/L)	1.01±0.59	1.07±0.80	2.887	0.472
Lp (a) (mg/L)	148.2±182.73	225.42±251.00	29.695	0.154
Serum calcium (g/L)	10.24±36.19	2.15±0.27	8.541	0.511
Hb (g/L)	116.15±36.32	118.63±22.82	163.484	0.026

Notes: Independent-samples t-test was performed. P < 0.05 indicates statistical significance.

Abbreviations: HCC, hepatocellular carcinoma; OM, ocular metastases; NOM, non-ocular metastases; CEA, carcinoembryonic antigen; CA-125, carbohydrate antigen 125; CA-199, carbohydrate antigen 199; CA-153, carbohydrate antigen 153; CA-724, carbohydrate antigen 724; FER, ferritin; ALP, alkaline phosphatase; TC, total cholesterol; TG, triglyceride; HDL, high-density lipoprotein; LDL, low-density lipoprotein; ApoA, apolipoproteinA; ApoB, apolipoproteinB; Lp, lipoprotein; Hb, hemoglobin.

Table 3 Risk Factors for OM in HCC Patients

Factors	B	Exp(B)	OR (95% CI)	P
CA-125 (u/mL)	0.005	1.005	1.003–1.007	<0.001
Hb (g/L)	0.030	1.030	1.004–1.058	0.026

Notes: Binary logistic analysis was applied. P < 0.05 indicates statistical significance.

Abbreviations: HCC, hepatocellular carcinoma; B, coefficient of regression; OR, odds ratio; CI, confidence interval; CA-125, carbohydrate antigen 125; OM, ocular metastases.

Table 4 The Cutoff Value, Sensitivity, Specificity, and AUC for Individual Risk Factors in Predicting OM in HCC Patients

Factor	Cutoff Value	Sensitivity (%)	Specificity (%)	AUC	P
CA-125 (u/mL)	115.78	90.0	73.9	0.877	< 0.001
Hb (g/L)	120.50	70.0	53.5	0.554	0.026
CA-125+Hb	95.03	100.0	6.8	0.431	0.003

Notes: Sensitivity and specificity were obtained at the cutoff value. P < 0.05 indicates statistical significance.

Abbreviations: HCC, hepatocellular carcinoma; AUC, area under the curve; OM, ocular metastasis; CA-125, carbohydrate antigen 125.

Figure 2 ROC curve shows CA-125 and Hb as single factors and as a combination for predicting OM in HCC patients.

Figure 3 Fundus camera image of HCC patients. (A) Retinal fundus photography. (B) Fundus fluorescence angiography.

Figure 4 Pathological images of HCC patients. (A) Hematoxylin-eosin (HE) staining. (B) Hepatocyte IHC staining.

Table 5 Studies on the OM from Different Cancers

Author	Year	Diseases with OM
Tei, et al^Citation14	2014	Rectal cancer
Shah, et al^Citation15	2014	Lung cancer
Hazan, et al^Citation16	2014	Choriocarcinoma
Cristina, et al^Citation17	2015	Primary bone leiomyosarcoma
Mercado, et al^Citation18	2016	Cutaneous melanoma
Fountas, et al^Citation19	2017	Thyroid cancer
Essadi, et al^Citation20	2017	Renal cancer
Levison, et al^Citation21	2018	Breast cancer
Chang, et al^Citation22	2018	Esophageal carcinoma
Wu, et al^Citation23	2019	Gastric carcinoma

Notes: The table summed up studies on OM from different types of cancer.

Abbreviation: OM, ocular metastasis.

Table 6 Studies on the Risk Factors of OM from Different Cancers

Author	Year	Diseases with OM	Increased Features	Decreased Features
Lin, et al^Citation24	2019	Lung cancer	Calcium, ALP, AFP, CEA, CA-125, CA-199, CYFRA21-1, TPSA	HB, NSE
Liu, et al^Citation25	2019	Breast cancer	ApoB	TC, TG, HDL, LDL, ApoAI, Lp (a)
Zhu, et al; Min, et al^Citation26,Citation27	2019 2020	Colorectal cancer	TC, HDL, CEA	TG, LDL

Note: The table summed up studies on the risk factors of OM from different types of cancer.

Abbreviation: OM, ocular metastasis.

Table 7 The Risk Factors for Metastases of Primary HCC

Author	Year	Histopathological Type	Metastatic Sites	Risk Factors
Lin, et al^Citation28	2003	HCC	Lung	Tumor size
Ogawa, et al^Citation29	2004	HCC	Distant metastasis	CD44v3
Xiang, et al^Citation30	2009	HCC	Bone	CXCR4
Lin, et al^Citation31	2010	HCC	Vessel	Aurora B
HSIAO SY et al^Citation32	2011	HCC	Brain	ALP
Chua TC, Morris DL^Citation33	2012	HCC	Bone	r-GT
Morimoto, et al^Citation34	2014	HCC	EHM	Platelet, DCP
Wan P et al^Citation35	2014	HCC	Pancreas	CA-199
Chen, et al^Citation36	2015	Small HCC	IHM and EHM	VEGF
Lee, et al^Citation37	2019	HCC	EHM	AFP

Note: The table summed up studies on risk factors of metastases from primary hepatocellular carcinoma.

Abbreviations: HCC, hepatocellular carcinoma; CD44v3, CD44 variant exon 3; CXCR4, CXC motif chemokine receptor 4; DCP, des-γ-carboxyprothrombin; VEGF, vascular endothelial growth factor; AFP, alpha-fetoprotein; EHM, extrahepatic metastasis; IHM, intrahepatic metastasis.

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