title: The nanomechanical signature of liver cancer tissues and its molecular origin.
abstract: Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the "gold standard" in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus distribution of surgically removed liver cancer tissues can serve as a mechanical fingerprint to evaluate the malignancy of liver cancer. Cirrhotic tissues shared the same LEP as normal tissues. However, a noticeable downward shift in the LEP was detected when the cirrhotic tissues progressed to a malignant state, making the tumor tissues more prone to microvascular invasion. Cell-level mechanistic studies revealed that the expression level of a Rho-family effector (mDia1) was consistent with the mechanical trend exhibited by the tissue. Our findings indicate that the mechanical profiles of liver cancer tissues directly varied with tumor progression, providing an additional platform for the future diagnosis of HCC.
authors.affiliation: Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China. shi.yinghong@zs-hospital.sh.cn.
authors.forename: Mengxin
authors.initials: M
authors.lastname: Tian
authors.forename: Yiran
authors.initials: Y
authors.lastname: Li
authors.forename: Weiren
authors.initials: W
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.forename: Xifei
authors.initials: X
authors.lastname: Jiang
authors.forename: Xinyan
authors.initials: X
authors.lastname: Wang
authors.forename: Zhenbin
authors.initials: Z
authors.lastname: Ding
authors.forename: Yuanfei
authors.initials: Y
authors.lastname: Peng
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.forename: Yi
authors.initials: Y
authors.lastname: Cao
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Shi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D055119:Elastic Modulus; D000080865:Formins; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D036103:Nanotechnology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D000075024:rhoC GTP-Binding Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C108962:DIAPH1 protein, human; D000080865:Formins; D034741:RNA, Small Interfering; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein