Current Opinions on the Relationship Between CMTM Family and Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a typically malignant tumor in the digestive system. The mortality of HCC ranks third place in the world, second only to lung cancer and colorectal cancer. For the characteristics of high invasiveness, high metastasis, high recurrence rate as well as short survival time, HCC treatment has always been difficult in clinical practice. Many causes have contributed to the appearance of these features, including insidious onset, high degree of malignancy, lack of effective early molecular diagnostic markers, and disease prediction models. The human chemokine-like factor superfamily (CMTMs) is a new gene family consisting of CKLF and CMTM1-CMTM8. CMTMs have a marvel domain which can activate and chemotaxis immune cells. Many studies have reported that CMTMs are involved in the regulation of cell growth and development, and play an important role in the malignant progression of the immune system and reproductive system, especially in the development of tumors. In this review, we summarized the structure and function of the human CMTMs, the relationship between its family members and HCC, the prognostic value, potential functions, and mechanisms in HCC. CMTMs could provide a new diagnostic and therapeutic target in clinical practice for patients with HCC.

Keywords:

• CMTM family
• hepatocellular carcinoma
• diagnosis
• treatment

Abbreviations

HCC, Hepatocellular carcinoma; IARC, International Agency for Research on Cancer; BCLC, Barcelona Clinic Liver Cancer; CMTM/CKLFSF, Chemokine-like factor superfamily; CKLF, chemokine-like factor; CMTM1-8, chemokine-like factor-like MARVEL transmembrane domain-containing family member 1-8; TM4SF, transmembrane 4 superfamily; IL6, Interleukin-6; STAT3, signal transducer and activator of transcription 3; KLT, Kanglaite; CDDP, cisplatin; HepG2, human hepatocellular carcinomas, NF-κB, nuclear factor κ-light-chain-enhancer of activated B cells; IHC, immunohistochemistry; TCGA, the Cancer Genome Atlas; ELISA; HBV, hepatitis B virus; ALT, Alanine transaminase; AST, aspartate amino transferase; ROC, receiver operating characteristic curve; ZEB1/ZEB2, zinc finger E box binding homeobox protein 1/2; EMT, epithelial-mesenchymal transformation; PC, prostate cancer; JAK2, Janus Kinase; m6A, N6 methyladenosine; lncRNAs, long non-coding RNAs; TNM stage, tumor node metastasis stage; PD-L1, programmed cell death-ligand 1; AKT, the serine/threonine kinase; EGFR, epidermal growth factor receptor; SNPs, single nucleotide polymorphisms; AFP, α-fetoprotein; TACE, trans-arterial chemoembolization; CTL, cytotoxic T-Lymphocyte; OS, overall survival; MTM, macro trabecular massive; DFS, progression-free survival; CDK2, cycle-dependent kinases 2.

Acknowledgments

All authors contributed significantly to the work reported, participated in drafting, revising or critically commenting on the article; gave final approval for the published version of the article; agreed to the journal in which the work was delivered and agreed to be responsible for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This research was funded by National Natural Science Foundation of China, grant number 82060621.