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Journal of Peking University (Health Sciences) ›› 2021, Vol. 53 ›› Issue (4): 710-715. doi: 10.19723/j.issn.1671-167X.2021.04.015

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Serum LAPTM4B-35 protein as a novel diagnostic marker for hepatocellular carcinoma

PANG Yong,ZHANG Sha,YANG Hua,ZHOU Rou-li()   

  1. Department of Cell Biology, Peking University School of Basic Medical Sciences, Beijing 100191, China
  • Received:2020-05-11 Online:2021-08-18 Published:2021-08-25
  • Contact: Rou-li ZHOU E-mail:rlzhou@bjmu.edu.cn
  • Supported by:
    Beijing Municipal Education Commission ChanXueYan Build Cooperation Projects(ZH100010502)

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Abstract:

Objective: LAPTM4B-35 protein is one of the isoforms that are encoded by a cancer driver gene, LAPTM4B. This gene was primarily found and identified in our lab of Peking University School of Basic Medical Sciences. The LAPTM4B-35 protein and its encoded mRNA are significantly over-expressed in a variety of cancers, such as hepatocellular carcinoma (HCC), lung cancers (including non small-cell lung cancer and small-cell lung cancer), stomach cancer, colorectal carcinoma, pancreatic cancer, gallbladder cancer, cholangiocarcinoma, breast cancer, prostate cancer, ovarian cancer, cervical cancer, endometrial cancer, and so on. It has firmly demonstrated through lab experiments either in vivo or in vitro, as well as clinical studies that the over-expression of LAPTM4B-35 can promote cancer growth, metastasis, and multidrug resistance. Specially, the expressive level of LAPTM4B-35 is associa-ted with recurrence of HCC. The aim of this study is to identify the release of LAPTM4B-35 protein from hepatocellular carcinoma into blood of HCC patients and into the medium of cultured HCC cells, and to identify its possible form of LAPTM4B-35 protein existed in blood and cell culture medium, as well as to explore the possibility of LAPTM4B-35 protein as a novel HCC biomarker for diagnosis of HCC and prognosis of HCC patients. Methods: Immunobloting (Western blot) and enzyme-linked immunosorbent assay (ELISA) were used for identification of LAPTM4B-35 protein in the blood of HCC patients and normal individuals. Ultrafiltration and ultracentrifugation were used to isolate and purify exosomes from the culture medium of HCC cells. Results: LAPTM4B-35 protein existed in the blood from HCC patients and normal donors that were demonstrated through Western blot and ELISA. LAPTM4B-35 was also released into the culture medium of HCC cells in the form of exosomes. Preliminary experiments showed that the average and the median of LAPTM4B-35 protein level in the blood of HCC patients (n=43) were both significantly higher than that in the blood of normal donors (n=33) through sandwich ELISA. Conclusion: It is promising that the LAPTM4B-35 protein which is released from HCC cells in the form of exosomes into their extraenvironment may be exploited as a novel cancer biomarker for HCC serological diagnosis.

Key words: Hepatocellular carcinoma, Exosomes, LAPTM4B-35, Biomarkers, tumor

CLC Number: 

  • R735.7

Figure 1

Western blot analysis of LAPTM4B-35 protein in serum of healthy individual and hepatocellular carcinoma patients P1 and P2, serum from HCC patients; H1, serum from normal indivi-dual."

Figure 2

Direct ELISA analysis of LAPTM4B-35 protein in serum of hepatocellular carcinoma patients * P<0.001, serum group vs. blank control group."

Figure 3

SDS-PAGE profiles of cellular extracts and exosomes from BEL-7402 hepatocellular carcinoma cells 1, molecular marker; 2, cellular extracts; 3, exosomes."

Figure 4

Western blot profiles of LAPTM4B-35 protein in membrance extracts from hepatocellular carcinoma tissues and exosomes from BEL-7402 hepatocellular carcinoma cells 1 and 2, tumor tissues; 3 and 4, exosomes."

Figure 5

LAPTM4B-35 protein in exosomes identified by direct ELISA * P<0.001, exosomes group vs. blank control group."

Figure 6

LAPTM4B-35 protein levels in serum from normal individuals and hepatocellular carcinoma patients detected by sandwich ELISA P<0.001, normal vs. HCC. Normal, normal individuals (n=33); HCC, hepatocellular carcinoma patients (n=43)."

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