肝癌患者血清甲胎蛋白(AFP)水平与肿瘤大小的相关性※

Nasteho Haj Bashir,鲍海华

(1.青海大学,青海西宁810016;2.青海大学附属医院,青海 西宁810001)

1 INTRODUCTION

Hepatocellular carcinoma(HCC)is the most com-mon type of primary liver cancer[1]and ranks third in the world leading causes of cancer death[2].Primary hepatocellular carcinoma,around 75%to 80%are attributable to chronic viral diseases hepatitis B or C viral infection.Chronic infection with the hepatitis B virus(HBV)was noted to be associated with the development of HCC in 1970[3].HBV infection is the origin of HCC in 85%of cases in endemic areas,however chronic HBV infection is only the third commoncauseof liver cancer[4].Other causes of HCC include alcohol abuse,exposure to aflatoxin B1,non-alcoholic fatty liver disease and certain inherited metabolic conditions such as hemochromatosis and alpha-1-antitrypsin deficiency.Nearly half of patients with primary HCC died due to lymph node metastasis[5].Because many patients with early stage are asymptomatic,HCC is often diagnosed late.Cirrhosis is present in 80%～90%of patientswith HCC,so early detection is extremely important for effective treatment.Currently the most used methods diagnosis of HCC are imaging and determination of serum AFP concentration.Compared with other serum markers,AFP has been used as gold standard all over the world[6].AFP is a valuable biomarker for HCC diagnosis;since 1970,majority of HCC patientswere detected at late stage accompanied by clinicalmanifestations[7].AFP is a kind of glycoprotein that transports a great variety of molecules.It is usually produced by liver,yolk sac and gastrointestinal tract during the development of fetus and newborn.Once it reaches the highest concentration in the second trimester,its levels declining and only a small amount of the substance can be detected in the blood[8].Sometimes,in the earlier stages of HCC,AFP levels increased and dropped down in the late stage of its progression.In addition,the increasing of AFP is not only related to acute and chronic viral hepatitis,but also to hepatitis C caused cirrhosis.AFP also increased more in patients with gastrointestinal tumors[9].AFP also increased during pregnancy[10].According to their binding capability to Lens Culinaris Agglutinin(LCA).Total AFP can be divided into three different glycoforms,AFP-L1,AFP-L2,and AFP-L3.Among them,the increasing of AFP-L3 is the LCA-bound fraction of AFP,which is related to tumor size,malignant features,and up regulation of liver function.However,there is evidence that AFP plays an important role in tumor growth and cell differentiation.At present,serum AFP is themost important serum marker in the diagnosis of HCC[11].The final diagnosis of chronic hepatic impairment,especially cirrhosis,should be combined with ultrasound and computer tomography(CT)togetherwith analysis of serology[12].AFP significantly improved the detection rate of early stage HCC,whichmay be the preferred surveillance strategy for patientswith cirrhosis before superior surveillance strategies are available.A studyhas beenreported that AFP has correlation with tumor size in HCC[13].The aim of this study was detected correlation between the serum AFP levels and tumor size in HCC.

2 MATERIAL AND METHODS

2.1 Subjects and examinations

474 patients(averaged 54.50±10.31 years old,ranged 25-81 years old)with primary HCC were analyzed retrospectively.Datacollected contained male and female(385,89),during January 2014 to December 2018,that include the history of hepatitis,level of serum AFP and tumor size.Themeasurement of tumor sizes by whole abdomenCT scan or MRI were also included in the documented data.The diagnosis of HCC was based on typical imaging features,that was,“fast wash in and fastwash out”in decimic enhancement CT or MRI(Figure 1).Serum AFP level,anti-hepatitis C virus(HCV)and HBsAg were also measured using standard enzyme linked immunosorbentassay technique(ELISA).

2.2 Statisticalmethods

According to the tumor size,the fundamental AFP levelwas divided into six levels a：Group IAFP≤20(ng/dL),Group II AFP=21～499(ng/dL),Group IIIAFP=500～899(ng/dL),Group IV AFP=900～1499(ng/dL),Group V AFP=1500～1999(ng/dL),Group VIAFP≥2000(ng/dL).According the normal AFP,the patients were divided into 3 groups：Group A(＜5cm),group B(5～10cm)and group C(11～20cm).Tumor size less than 5 cm,tumor size ranged from 5 to 9 cm,tumor size ranged from10 to 20 cm.The AFP levelswere also counted as AFP≤20(ng/dL),AFP=21～499(ng/dL),AFP=500～899(ng/dL),AFP=900～1499(ng/dL),AFP=1500～1999(ng/dL),and AFP≥2000(ng/dL).

The correlation between AFP level and tumor size was analyzed by Spearman′s correlation.P value＜0.05 was considered as significant correlation.Descriptive statisticswere obtained for the variableswhere applicable,using SPSSversion 24(IBM,Armonk,New York).

Figure 1 Im ages from a 58-year-old female w ith hepatocellular carcinom a mainly in right lope of the liver on CT scan

3 .Results

3.1 Correlation of tu mor size and AFP

A total of 474 cases were included,including 385 males(81.22%)and 89 females(18.78%).Themean age of patientswas 54.50±10.31 years old(range 25～81).A-mong all the patients,93.25%of patientswerediagnosedhepatitis B,17(3.59%)and 7(1.48%)were diagnosedwithhepatitis C and hepatitis A.There are 8(1.68%)patientswere infected by more than one type of hepatitis virus,themean tumor size was 2.049±0.547 cm.The mean serum AFP level was 3.120±0.926(ng/dL).This suggested that as tumor sizes increase,the AFP levels also increase(Table 1).In addition,according to the tumor size,patients were divided into three levels.Nearly half of patients′(207,43.67%)tumor sizeswere between 5～10 cm.Therewere 122(25.74%)patients′tumor less than 5 cm,and 145(30.59%)patients′tumor between 10～20 cm.The AFP level group were 145(30.59%),130(27.42%),31(6.54%),10(2.11%),7(1.48%)and 151(31.86%)respectively.That increased of serum AFP was associated with increased tumor size of HCC,the serum AFP level was statistically correlated with tumor size(rs=0.198,P=0.0001)as depicted in Table 1.

Table 1 Correlation of tumor size and serum AFP in HCC(100%)

3.2 Distribution of patientswith normal AFP according to tumor size

54.64 %of the 474 AFP patients had normal serum AFP level.Among the normal AFP level patients,about 56(21.62%)patient′s tumor size less than 5 cm,most(44.02%)patients′tumor was between 5 cm and 10 cm,and 89(34.36%)patient′s tumor size ranged from 11 to 20 cmas shown in Table 2.

Table 2 The Distribution of patients w ith normal AFP according to tumor size

4 DISCUSSION

Approximately 90%of the malignant liver tumors are primary HCC[14].The findings from this study confirm that there was a correlation between serum AFP level and tumor size in HCC.HBV is one of the most common chronic infections worldwide.It was estimated that 257 million chronic infections were the main causes of HCC worldwide.Although the prevalence of HBV infections varies in different geographical regions,the incidence rate is the highestamong the developing countryin sub Saharan Africa and East Asia.HBV is transmitted through mother to child transmission,iatrogenic infection,blood transfusion,close life contact and sexual transmission.Our research showed that themost common cause of HCC is HBV infection.In this study over 90%of patients have HBV while 3.59%have HCV,and 1.48%for HAV.In China,liver cancer patientswere mostly caused by the developmentof hepatitis B cirrhosis with poor liver function.In addition,HCC patients often missed liver transplant due to lacking of donors consequently the treatment therapy for HCC patients may not strictly follow the BCLC algorithm,RFA or TACE may be chosen more frequently instead[15].The prevalence rate ofmalewas higher than that of female,and the gender ratio varies according to geographical region.Primary liver cancer was a common malignant tumor in many countries including China.Its incidence rate,recurrence rate and mortality rate are high.HCC was the most common fatalmalignancy in adult males on the continent,and the third most common fatalmalignancy in women[16].The incidence and mortality of female HCC patientswere significantly lower than that ofmale patients.Although there was a difference in the lifestyle between men and women,women aftermenopause had higher possibility to develop HCC,which indicates that the estrogen may have protective effects on HCC development and progression[17].Another new study shows that adiponectin induction and effects on tumor growth inmale and female mice as well as adiponectin serum levels in men and women.And that the lower adiponectin levels found in men account for the increased incidence of HCC[18],which means that the level of hormone secreted by adipocytes in women is high,which can prevent liver cell from becoming cancerous.In this study showed that patients serum AFP concentrations were progressively higher with increasing tumor sizes,which is consistent with the.Resultsof previous studies in the present study,AFP positivity is analyzed to check its correlation with the size of tumor.We found that30.59%had AFP level of less than 20 ng/dL,27.42%had levels Between 21～499 ng/dL and 500～899 ng/dL had 6.54%,900～1499 ng/dL had 2.11%and 1500～1999 ng/dL had 1.48%levels equal ormore than 2000 ng/dL had 31.86%.The highest AFP levelwasmore than 2000 ng/ml.According to tumor size with normal AFP 259 categorized in to three＜5 cm had 21.62%,and 5～10 cm 44.02%also 11～20 cm 34.36%.There was a significant relationship between serum AFP level with tumor size.This result was in line with the prior study by Abbasi A et al[10],which reported a relation between serum AFP level and size of the tumor(r=0.472)with a P-value＜0.0001.And Dr.Khalil ur Rehman etal.also reported(r=0.668)with a P-value＜0.05.Treatment options for HCC are very limited,as it is often diagnosed at a late stage Imaging of the liver is an important technique in the detection and diagnosis of HCC.Due to surveillance programs for patients at high risk for the development of hepatocellular carcinoma,an increasing number of tumors are currently diagnosed at an early and asymptomatic stage[19].When HCC is diagnosed at an early stage,resection or liver transplantation can be an effective treatment[20].Liver cirrhosis is a well-known risk factor for primary liver cancer among patients with viral hepatitis,but it also increases the risk of extrahepatic malignancies.Cirrhosis due chronic hepatitis B might be reversible in some patients who respond to antiviral therapy previous researchers have indicated that combination of GPC-3 and AFP Improves the sensitivity and accuracy of HCC diagnosis[21]which is not attempted in our study.GPC-3Could be a useful immune histochemical marker to distinguish between benign and malignant hepatocellularmass lesions[22].

5 .ConclusionS

This study suggests that serum AFP has significant correlation with the size of tumor(P=0.0001).AFP is a useful biomarker which can help clinicians to adopt preventive strategies for patients at high risk and further improve outcome of patient with HCC.However,clinicians should remember that some patientswith primary hepatic cancer will have normal AFP levels,and imaging technology is also needed.