Skip to main content
Top
Published in: BMC Gastroenterology 1/2023

Open Access 01-12-2023 | Hepatocellular Carcinoma | Research article

A novel predictive model of microvascular invasion in hepatocellular carcinoma based on differential protein expression

Authors: Zhenglu Wang, Lei Cao, Jianxi Wang, Hanlin Wang, Tingting Ma, Zhiqi Yin, Wenjuan Cai, Lei Liu, Tao Liu, Hengde Ma, Yamin Zhang, Zhongyang Shen, Hong Zheng

Published in: BMC Gastroenterology | Issue 1/2023

Login to get access

Abstract

Background

This study aims to construct and verify a nomogram model for microvascular invasion (MVI) based on hepatocellular carcinoma (HCC) tumor characteristics and differential protein expressions, and explore the clinical application value of the prediction model.

Methods

The clinicopathological data of 200 HCC patients were collected and randomly divided into training set and validation set according to the ratio of 7:3. The correlation between MVI occurrence and primary disease, age, gender, tumor size, tumor stage, and immunohistochemical characteristics of 13 proteins, including GPC3, CK19 and vimentin, were statistically analyzed. Univariate and multivariate analyzes identified risk factors and independent risk factors, respectively. A nomogram model that can be used to predict the presence of MVI was subsequently constructed. Then, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were conducted to assess the performance of the model.

Results

Multivariate logistic regression analysis indicated that tumor size, GPC3, P53, RRM1, BRCA1, and ARG were independent risk factors for MVI. A nomogram was constructed based on the above six predictors. ROC curve, calibration, and DCA analysis demonstrated the good performance and the clinical application potential of the nomogram model.

Conclusions

The predictive model constructed based on the clinical characteristics of HCC tumors and differential protein expression patterns could be helpful to improve the accuracy of MVI diagnosis in HCC patients.
Appendix
Available only for authorised users
Literature
1.
go back to reference Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.CrossRefPubMed Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.CrossRefPubMed
3.
go back to reference Hou YF, Wei YG, Yang JY, Wen TF, Xu MQ, Yan LN, et al. Microvascular invasion patterns affect survival in hepatocellular carcinoma patients after second hepatectomy. J Surg Res. 2016;200(1):82–90.CrossRefPubMed Hou YF, Wei YG, Yang JY, Wen TF, Xu MQ, Yan LN, et al. Microvascular invasion patterns affect survival in hepatocellular carcinoma patients after second hepatectomy. J Surg Res. 2016;200(1):82–90.CrossRefPubMed
4.
go back to reference Wang H, Wu MC, Cong WM. Microvascular invasion predicts a poor prognosis of solitary hepatocellular carcinoma up to 2 cm based on propensity score matching analysis. Hepatol Res. 2019;49(3):344–54.CrossRefPubMed Wang H, Wu MC, Cong WM. Microvascular invasion predicts a poor prognosis of solitary hepatocellular carcinoma up to 2 cm based on propensity score matching analysis. Hepatol Res. 2019;49(3):344–54.CrossRefPubMed
5.
go back to reference Wang H, Qian YW, Wu MC, Cong WM. Liver resection is justified in patients with BCLC intermediate stage hepatocellular carcinoma without microvascular invasion. J Gastrointest Surg. 2020;24(12):2737–47.CrossRefPubMed Wang H, Qian YW, Wu MC, Cong WM. Liver resection is justified in patients with BCLC intermediate stage hepatocellular carcinoma without microvascular invasion. J Gastrointest Surg. 2020;24(12):2737–47.CrossRefPubMed
6.
go back to reference Yu YQ, Wang L, Jin Y, Zhou JL, Geng YH, Jin X, et al. Identification of serologic biomarkers for predicting microvascular invasion in hepatocellular carcinoma. Oncotarget. 2016;7(13):16362–71.CrossRefPubMedPubMedCentral Yu YQ, Wang L, Jin Y, Zhou JL, Geng YH, Jin X, et al. Identification of serologic biomarkers for predicting microvascular invasion in hepatocellular carcinoma. Oncotarget. 2016;7(13):16362–71.CrossRefPubMedPubMedCentral
7.
go back to reference Zhao X, Liu Y, Yu S. Long noncoding RNA AWPPH promotes hepatocellular carcinoma progression through YBX1 and serves as a prognostic biomarker. Biochim Biophys Acta Mol Basis Dis. 2017;1863(7):1805–16.CrossRefPubMed Zhao X, Liu Y, Yu S. Long noncoding RNA AWPPH promotes hepatocellular carcinoma progression through YBX1 and serves as a prognostic biomarker. Biochim Biophys Acta Mol Basis Dis. 2017;1863(7):1805–16.CrossRefPubMed
8.
go back to reference Sheng X, Ji Y, Ren GP, Lu CL, Yun JP, Chen LH, et al. A standardized pathological proposal for evaluating microvascular invasion of hepatocellular carcinoma: a multicenter study by LCPGC. Hepatol Int. 2020;14(6):1034–47.CrossRefPubMed Sheng X, Ji Y, Ren GP, Lu CL, Yun JP, Chen LH, et al. A standardized pathological proposal for evaluating microvascular invasion of hepatocellular carcinoma: a multicenter study by LCPGC. Hepatol Int. 2020;14(6):1034–47.CrossRefPubMed
9.
go back to reference Hu HT, Wang Z, Huang XW, Chen SL, Zheng X, Ruan SM, et al. Ultrasound-based radiomics score: a potential biomarker for the prediction of microvascular invasion in hepatocellular carcinoma. Eur Radiol. 2019;29(6):2890–901.CrossRefPubMed Hu HT, Wang Z, Huang XW, Chen SL, Zheng X, Ruan SM, et al. Ultrasound-based radiomics score: a potential biomarker for the prediction of microvascular invasion in hepatocellular carcinoma. Eur Radiol. 2019;29(6):2890–901.CrossRefPubMed
10.
go back to reference Feng J, Zhu R, Chang C, Yu L, Cao F, Zhu G, et al. CK19 and Glypican 3 expression profiling in the prognostic indication for patients with HCC after surgical resection. PLoS ONE. 2016;11(3):e0151501.CrossRefPubMedPubMedCentral Feng J, Zhu R, Chang C, Yu L, Cao F, Zhu G, et al. CK19 and Glypican 3 expression profiling in the prognostic indication for patients with HCC after surgical resection. PLoS ONE. 2016;11(3):e0151501.CrossRefPubMedPubMedCentral
11.
go back to reference Lin J, Lin W, Ye Y, Wang L, Chen X, Zang S, et al. Kindlin-2 promotes hepatocellular carcinoma invasion and metastasis by increasing Wnt/beta-catenin signaling. J Exp Clin Cancer Res. 2017;36(1):134.CrossRefPubMedPubMedCentral Lin J, Lin W, Ye Y, Wang L, Chen X, Zang S, et al. Kindlin-2 promotes hepatocellular carcinoma invasion and metastasis by increasing Wnt/beta-catenin signaling. J Exp Clin Cancer Res. 2017;36(1):134.CrossRefPubMedPubMedCentral
12.
go back to reference Nagtegaal ID, Odze RD, Klimstra D, Paradis V, Rugge M, Schirmacher P, et al. The 2019 WHO classification of tumours of the digestive system. Histopathology. 2020;76(2):182–8.CrossRefPubMed Nagtegaal ID, Odze RD, Klimstra D, Paradis V, Rugge M, Schirmacher P, et al. The 2019 WHO classification of tumours of the digestive system. Histopathology. 2020;76(2):182–8.CrossRefPubMed
13.
go back to reference Shen J, Wen T, Chen W, Lu C, Yan L, Yang J. Model predicting the microvascular invasion and satellite lesions of hepatocellular carcinoma after hepatectomy. ANZ J Surg. 2018;88(11):E761–6.CrossRefPubMed Shen J, Wen T, Chen W, Lu C, Yan L, Yang J. Model predicting the microvascular invasion and satellite lesions of hepatocellular carcinoma after hepatectomy. ANZ J Surg. 2018;88(11):E761–6.CrossRefPubMed
14.
go back to reference Ziogas IA, Tsoulfas G. Advances and challenges in laparoscopic surgery in the management of hepatocellular carcinoma. World J Gastrointest Surg. 2017;9(12):233–45.CrossRefPubMedPubMedCentral Ziogas IA, Tsoulfas G. Advances and challenges in laparoscopic surgery in the management of hepatocellular carcinoma. World J Gastrointest Surg. 2017;9(12):233–45.CrossRefPubMedPubMedCentral
15.
go back to reference Zhang D, Xu A. Application of dual-source CT perfusion imaging and MRI for the diagnosis of primary liver cancer. Oncol Lett. 2017;14(5):5753–8.PubMedPubMedCentral Zhang D, Xu A. Application of dual-source CT perfusion imaging and MRI for the diagnosis of primary liver cancer. Oncol Lett. 2017;14(5):5753–8.PubMedPubMedCentral
17.
go back to reference Huang M, Liao B, Xu P, Cai H, Huang K, Dong Z, et al. Prediction of microvascular invasion in hepatocellular carcinoma: preoperative Gd-EOB-DTPA-dynamic enhanced MRI and histopathological correlation. Contrast Media Mol Imaging. 2018;2018:9674565.CrossRefPubMedPubMedCentral Huang M, Liao B, Xu P, Cai H, Huang K, Dong Z, et al. Prediction of microvascular invasion in hepatocellular carcinoma: preoperative Gd-EOB-DTPA-dynamic enhanced MRI and histopathological correlation. Contrast Media Mol Imaging. 2018;2018:9674565.CrossRefPubMedPubMedCentral
18.
go back to reference Li N, Wei L, Liu X, Bai H, Ye Y, Li D, et al. A frizzled-like cysteine-rich domain in Glypican-3 mediates Wnt binding and regulates hepatocellular carcinoma tumor growth in mice. Hepatology. 2019;70(4):1231–45.CrossRefPubMed Li N, Wei L, Liu X, Bai H, Ye Y, Li D, et al. A frizzled-like cysteine-rich domain in Glypican-3 mediates Wnt binding and regulates hepatocellular carcinoma tumor growth in mice. Hepatology. 2019;70(4):1231–45.CrossRefPubMed
19.
go back to reference Bykov VJN, Eriksson SE, Bianchi J, Wiman KG. Targeting mutant p53 for efficient cancer therapy. Nat Rev Cancer. 2018;18(2):89–102.CrossRefPubMed Bykov VJN, Eriksson SE, Bianchi J, Wiman KG. Targeting mutant p53 for efficient cancer therapy. Nat Rev Cancer. 2018;18(2):89–102.CrossRefPubMed
20.
go back to reference Parrotta R, Okonska A, Ronner M, Weder W, Stahel R, Penengo L, et al. A novel BRCA1-associated protein-1 isoform affects response of mesothelioma cells to drugs impairing BRCA1-mediated DNA repair. J Thorac Oncol. 2017;12(8):1309–19.CrossRefPubMed Parrotta R, Okonska A, Ronner M, Weder W, Stahel R, Penengo L, et al. A novel BRCA1-associated protein-1 isoform affects response of mesothelioma cells to drugs impairing BRCA1-mediated DNA repair. J Thorac Oncol. 2017;12(8):1309–19.CrossRefPubMed
21.
go back to reference Chen L, Yang L, Qiao F, Hu X, Li S, Yao L, et al. High levels of nucleolar spindle-associated protein and reduced levels of BRCA1 expression predict poor prognosis in triple-negative breast cancer. PLoS ONE. 2015;10(10):e0140572.CrossRefPubMedPubMedCentral Chen L, Yang L, Qiao F, Hu X, Li S, Yao L, et al. High levels of nucleolar spindle-associated protein and reduced levels of BRCA1 expression predict poor prognosis in triple-negative breast cancer. PLoS ONE. 2015;10(10):e0140572.CrossRefPubMedPubMedCentral
22.
go back to reference Mader CC, Oser M, Magalhaes MA, Bravo-Cordero JJ, Condeelis J, Koleske AJ, et al. An EGFR-Src-Arg-cortactin pathway mediates functional maturation of invadopodia and breast cancer cell invasion. Cancer Res. 2011;71(5):1730–41.CrossRefPubMedPubMedCentral Mader CC, Oser M, Magalhaes MA, Bravo-Cordero JJ, Condeelis J, Koleske AJ, et al. An EGFR-Src-Arg-cortactin pathway mediates functional maturation of invadopodia and breast cancer cell invasion. Cancer Res. 2011;71(5):1730–41.CrossRefPubMedPubMedCentral
23.
go back to reference Liu Z, Zhang R, Sun Z, Yao J, Yao P, Chen X, et al. Identification of hub genes and small-molecule compounds in medulloblastoma by integrated bioinformatic analyses. PeerJ. 2020;8:e8670.CrossRefPubMedPubMedCentral Liu Z, Zhang R, Sun Z, Yao J, Yao P, Chen X, et al. Identification of hub genes and small-molecule compounds in medulloblastoma by integrated bioinformatic analyses. PeerJ. 2020;8:e8670.CrossRefPubMedPubMedCentral
24.
go back to reference Huang S, Yang J, Fong S, Zhao Q. Artificial intelligence in cancer diagnosis and prognosis: Opportunities and challenges. Cancer Lett. 2020;471:61–71.CrossRefPubMed Huang S, Yang J, Fong S, Zhao Q. Artificial intelligence in cancer diagnosis and prognosis: Opportunities and challenges. Cancer Lett. 2020;471:61–71.CrossRefPubMed
25.
go back to reference Sato M, Morimoto K, Kajihara S, Tateishi R, Shiina S, Koike K, et al. Machine-learning approach for the development of a novel predictive model for the diagnosis of hepatocellular carcinoma. Sci Rep. 2019;9(1):7704.CrossRefPubMedPubMedCentral Sato M, Morimoto K, Kajihara S, Tateishi R, Shiina S, Koike K, et al. Machine-learning approach for the development of a novel predictive model for the diagnosis of hepatocellular carcinoma. Sci Rep. 2019;9(1):7704.CrossRefPubMedPubMedCentral
26.
go back to reference Nunes N, Ambler G, Foo X, Widschwendter M, Jurkovic D. Prospective evaluation of IOTA logistic regression models LR1 and LR2 in comparison with subjective pattern recognition for diagnosis of ovarian cancer in an outpatient setting. Ultrasound Obstet Gynecol. 2018;51(6):829–35.CrossRefPubMed Nunes N, Ambler G, Foo X, Widschwendter M, Jurkovic D. Prospective evaluation of IOTA logistic regression models LR1 and LR2 in comparison with subjective pattern recognition for diagnosis of ovarian cancer in an outpatient setting. Ultrasound Obstet Gynecol. 2018;51(6):829–35.CrossRefPubMed
27.
go back to reference He Y, Guo J, Ding X, van Ooijen PMA, Zhang Y, Chen A, et al. Convolutional neural network to predict the local recurrence of giant cell tumor of bone after curettage based on pre-surgery magnetic resonance images. Eur Radiol. 2019;29(10):5441–51.CrossRefPubMed He Y, Guo J, Ding X, van Ooijen PMA, Zhang Y, Chen A, et al. Convolutional neural network to predict the local recurrence of giant cell tumor of bone after curettage based on pre-surgery magnetic resonance images. Eur Radiol. 2019;29(10):5441–51.CrossRefPubMed
28.
go back to reference Radakovich N, Nagy M, Nazha A. Machine learning in haematological malignancies. Lancet Haematol. 2020;7(7):e541–50.CrossRefPubMed Radakovich N, Nagy M, Nazha A. Machine learning in haematological malignancies. Lancet Haematol. 2020;7(7):e541–50.CrossRefPubMed
29.
go back to reference Cucchetti A, Piscaglia F, Grigioni AD, Ravaioli M, Cescon M, Zanello M, et al. Preoperative prediction of hepatocellular carcinoma tumour grade and micro-vascular invasion by means of artificial neural network: a pilot study. J Hepatol. 2010;52(6):880–8.CrossRefPubMed Cucchetti A, Piscaglia F, Grigioni AD, Ravaioli M, Cescon M, Zanello M, et al. Preoperative prediction of hepatocellular carcinoma tumour grade and micro-vascular invasion by means of artificial neural network: a pilot study. J Hepatol. 2010;52(6):880–8.CrossRefPubMed
30.
go back to reference Xu X, Zhang HL, Liu QP, Sun SW, Zhang J, Zhu FP, et al. Radiomic analysis of contrast-enhanced CT predicts microvascular invasion and outcome in hepatocellular carcinoma. J Hepatol. 2019;70(6):1133–44.CrossRefPubMed Xu X, Zhang HL, Liu QP, Sun SW, Zhang J, Zhu FP, et al. Radiomic analysis of contrast-enhanced CT predicts microvascular invasion and outcome in hepatocellular carcinoma. J Hepatol. 2019;70(6):1133–44.CrossRefPubMed
Metadata
Title
A novel predictive model of microvascular invasion in hepatocellular carcinoma based on differential protein expression
Authors
Zhenglu Wang
Lei Cao
Jianxi Wang
Hanlin Wang
Tingting Ma
Zhiqi Yin
Wenjuan Cai
Lei Liu
Tao Liu
Hengde Ma
Yamin Zhang
Zhongyang Shen
Hong Zheng
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2023
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/s12876-023-02729-z

Other articles of this Issue 1/2023

BMC Gastroenterology 1/2023 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.