|Table of Contents|

Predictive value of TTN mutation-related gene characteristics on prognosis of hepatocellular carcinoma

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 12
Page:
2275-2283
Research Field:
Publishing date:

Info

Title:
Predictive value of TTN mutation-related gene characteristics on prognosis of hepatocellular carcinoma
Author(s):
BI Yanqing1; HUANG Rong2; SONG Wei2; ZHANG Ziying3; TIAN Zixuan1; LIU Min1; BAO Han1; YAN Tao1; XIA Yuan1; ZHANG Nan1; ZHANG Xingguang1
1.Department of Biostatistics，Public Health College，Inner Mongolia Medical University，Inner Mongolia Hohhot 010110，China；2.Department of Biochemistry and Molecular Biology，State Key Laboratory of Medical Molecular Biology，Institute of Basic Medical Sciences，Chinese Academy of Medical Sciences and School of Basic Medicine，Peking Union Medical College，Beijing 100005，China；3.Department of Biostatistics，Basic Medical College，Inner Mongolia Medical University，Inner Mongolia Hohhot 010110，China.
Keywords:
TTN mutation; gene signature; prognosis; functional analysis; HCC
PACS:
R735.7
DOI:
10.3969/j.issn.1672-4992.2023.12.018
Abstract:
Objective:To find new effective biomarkers for early diagnosis and prognosis prediction of hepatocellular carcinoma（HCC).Methods:The transcriptomic and clinical data of HCC samples were downloaded from The Cancer Genome Atlas（TCGA).The mRNA abundance data and TTN mutation information from TCGA cohort were utilized to characterize a specific TTN mutation-associated signature according to gene expression differences between wild-type TTN and mutated TTN HCC patients.The genes related to the prognosis of HCC patients were screened by survival analysis，and the prognostic risk model was constructed by univariate Cox regression.After that，GO annotation，pathway enrichment analysis，Kyoto Encyclopedia of Genes and Genomes（KEGG) and gene set enrichment analysis（GSEA) were used to determine that the function of differentially expressed genes（DEGs) related to the prognosis of HCC patients.Results:Five genes，VAX1(ventral anterior homeobox 1)，MMP3（matrix metalloproteinase 3)，CXCL5（CXC-type chemokine 5)，TKTL1(transketolase-like protein 1) and KCNA3（voltage-gated potassium channel Kv1.3) determined by univariate Cox regression and Kaplan-Meier survival analysis constituted the overall survival（OS) prognostic gene characteristics of patients with HCC.Conclusion:Five TTN mutation-related genes，including VAX1，MMP3，CXCL5，TKTL1，and KCNA3，can be used as potential biomarkers and therapeutic targets for the survival and prognosis of HCC patients.

References:

［1］SUNG H，FERLAY J，SIEGEL RL，et al.Global cancer statistics 2020：GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］.CA Cancer J Clin,2021，71(3)：209-249.
［2］RAHIB L，SMITH BD，AIZENBERG R，et al.Projecting cancer incidence and deaths to 2030：the unexpected burden of thyroid，liver，and pancreas cancers in the United States［J］.Cancer Res,2014，74(11)：2913-2921.
［3］LIN DC，MAYAKONDA A，DINH HQ，et al.Genomic and epigenomic heterogeneity of hepatocellular carcinoma［J］.Cancer Res,2017，77(9)：2255-2265.
［4］TANG B，ZHU J，ZHAO Z，et al.Diagnosis and prognosis models for hepatocellular carcinoma patient's management based on tumor mutation burden［J］.J Adv Res,2021，33：153-165.
［5］NIU ZS，NIU XJ，WANG WH.Genetic alterations in hepatocellular carcinoma：An update［J］.World J Gastroenterol,2016，22(41)：9069-9095.
［6］KONG F，KONG D，YANG X，et al.Integrative analysis of highly mutated genes in hepatitis B virus-related hepatic carcinoma［J］.Cancer Med,2020，9(7)：2462-2479.
［7］WONG AM，DING X，WONG AM，et al.Unique molecular characteristics of NAFLD-associated liver cancer accentuate β-catenin/TNFRSF19-mediated immune evasion［J］.J Hepatol,2022，77(2)：410-423.
［8］SU C，WANG X，ZHOU J，et al.Titin mutation in circulatory tumor DNA is associated with efficacy to immune checkpoint blockade in advanced non-small cell lung cancer［J］.Transl Lung Cancer Res,2021，10(3)：1256-1265.
［9］LOESCHER CM，HOBBACH AJ，LINKE WA.Titin（TTN)：from molecule to modifications，mechanics，and medical significance［J］.Cardiovasc Res,2022，118(14)：2903-2918.
［10］ROMANO R，GHAHREMANI S，ZIMMERMAN T，et al.Reading frame repair of TTN truncation variants restores titin quantity and functions［J］.Circulation,2022，145(3)：194-205.
［11］JIANG AM，REN MD，LIU N，et al.Tumor mutation burden，immune cell infiltration，and construction of immune-related genes prognostic model in head and neck cancer［J］.Int J Med Sci,2021，18(1)：226-238.
［12］REES M，NIKOOPOUR R，FUKUZAWA A，et al.Making sense of missense variants in TTN-related congenital myopathies［J］.Acta Neuropathol,2021，141(3)：431-453.
［13］ZOU S，YE J，HU S，et al.Mutations in the TTN gene are a prognostic factor for patients with lung squamous cell carcinomas［J］.Int J Gen Med,2022，15：19-31.
［14］GEISTLINGER L，CSABA G，SANTARELLI M，et al.Toward a gold standard for benchmarking gene set enrichment analysis［J］.Brief Bioinform,2021，22(1)：545-556.
［15］MIKSCH RC，SCHOENBERG MB，WENIGER M，et al.Prognostic impact of tumor-infiltrating lymphocytes and neutrophils on survival of patients with upfront resection of pancreatic cancer［J］.Cancers（Basel),2019，11(1)：1129-1139.
［16］ZHANG S，ZENG Z，LIU Y，et al.Prognostic landscape of tumor-infiltrating immune cells and immune-related genes in the tumor microenvironment of gastric cancer［J］.Aging（Albany NY),2020，12(18)：17958-17975.
［17］QIU XT，SONG YC，LIU J，et al.Identification of an immune-related gene-based signature to predict prognosis of patients with gastric cancer［J］.World J Gastrointest Oncol,2020，12(8)：857-876.
［18］BAHCIVANCI B，SHAFIHA R，GKOUTOS GV，et al.Associating transcriptomics data with inflammatory markers to understand tumour microenvironment in hepatocellular carcinoma［J］.Cancer Med,2023，12(1)：696-711.
［19］SHI Y，GAO W，LYTLE NK，et al.Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring［J］.Nature,2019，569(7754)：131-135.
［20］ZHANG J，WANG J，QIAN Z，et al.CCR5 is associated with immune cell infiltration and prognosis of lung cancer［J］.J Thorac Oncol,2019，14(5)：e102-e103.
［21］ZHOU R，ZHANG J，ZENG D，et al.Immune cell infiltration as a biomarker for the diagnosis and prognosis of stage Ⅰ-Ⅲ colon cancer［J］.Cancer Immunol Immunother,2019，68(3)：433-442.
［22］HERMANS IF，RITCHIE DS，YANG J，et al.CD8+T cell-dependent elimination of dendritic cells in vivo limits the induction of antitumor immunity［J］.J Immunol,2000，164(6)：3095-3101.
［23］PENG F，ZHOU J，SHENG W，et al.Expression and significance of leukemia inhibitory factor in human pancreatic cancer［J］.National Medical Journal of China,2014，94(2)：90-95.
［24］PARK JY，PARK KH，BANG S，et al.CXCL5 overexpression is associated with late stage gastric cancer［J］.J Cancer Res Clin Oncol,2007，133(11)：835-840.
［25］BEGLEY LA，KASINA S，MEHRA R，et al.CXCL5 promotes prostate cancer progression［J］.Neoplasia,2008，10(3)：244-254.
［26］FRICK VO，RUBIE C，WAGNER M，et al.Enhanced ENA-78 and IL-8 expression in patients with malignant pancreatic diseases［J］.Pancreatology,2008，8(4-5)：488-497.
［27］WONG YF，CHEUNG TH，LO KW，et al.Identification of molecular markers and signaling pathway in endometrial cancer in Hong Kong Chinese women by genome-wide gene expression profiling［J］.Oncogene,2007，26(13)：1971-1982.
［28］MIYAZAKI H，PATEL V，WANG H，et al.Down-regulation of CXCL5 inhibits squamous carcinogenesis［J］.Cancer Res,2006，66(8)：4279-4284.
［29］WENTE MN，KEANE MP，BURDICK MD，et al.Blockade of the chemokine receptor CXCR2 inhibits pancreatic cancer cell-induced angiogenesis［J］.Cancer Lett,2006，241(2)：221-227.
［30］ENGLING US，MISSLER U，KERNER W.Time-resolved immunofluorometric assay for quantifying proinsulin in serum［J］.Clin Chem,1995，41(6 Pt 1)：942-953.
［31］ZHOU SL，DAI Z，ZHOU ZJ，et al.Overexpression of CXCL5 mediates neutrophil infiltration and indicates poor prognosis for hepatocellular carcinoma［J］.Hepatology,2012，56(6)：2242-2254.
［32］LIU Z，YANG L，XU J，et al.Enhanced expression and clinical significance of chemokine receptor CXCR2 in hepatocellular carcinoma［J］.J Surg Res,2011，166(2)：241-246.
［33］MIRSHAHI F，AQBI HF，CRESSWELL K，et al.Longitudinal studies can identify distinct inflammatory cytokines associated with the inhibition or progression of liver cancer［J］.Liver Int,2020，40(2)：468-472.
［34］HAIDER C，HNAT J，WAGNER R，et al.Transforming growth factor-β and axl induce CXCL5 and neutrophil recruitment in hepatocellular carcinoma［J］.Hepatology,2019，69(1)：222-236.
［35］KICMAN A，NICZYPORUK M，KULESZA M，et al.Utility of matrix metalloproteinases in the diagnosis，monitoring and prognosis of ovarian cancer patients［J］.Cancer Manag Res,2022，14：3359-3382.
［36］PIRATVISUTH T，TANWANDEE T，THONGSAWAT S，et al.Multimarker panels for detection of early stage hepatocellular carcinoma：A prospective，multicenter，case-control study［J］.Hepatol Commun,2022，6(4)：679-691.
［37］CHEN J，LI N，LIAN P，et al.Interaction of cyclophilin A with a novel binding protein，SR-25，and characterization of their expression pattern in Chinese hepatocellular carcinoma patients［J］.Oncol Lett,2016，12(6)：5254-5260.
［38］ZHANG M，DAI C，ZHU H，et al.Cyclophilin A promotes human hepatocellular carcinoma cell metastasis via regulation of MMP3 and MMP9［J］.Mol Cell Biochem,2011，357(1-2)：387-395.
［39］WANG W，LIN H，ZHOU L，et al.MicroRNA-30a-3p inhibits tumor proliferation，invasiveness and metastasis and is downregulated in hepatocellular carcinoma［J］.Eur J Surg Oncol,2014，40(11)：1586-1594.
［40］PELTONEN R，AHOPELTO K，HAGSTROM J，et al.High TKTL1 expression as a sign of poor prognosis in colorectal cancer with synchronous rather than metachronous liver metastases［J］.Cancer Biol Ther,2020，21(9)：826-831.
［41］ZHANG S，YANG JH，GUO CK，et al.Gene silencing of TKTL1 by RNAi inhibits cell proliferation in human hepatoma cells［J］.Cancer Lett,2007，253(1)：108-114.
［42］BHARTI K，GASPER M，BERTUZZI S，et al.Lack of the ventral anterior homeodomain transcription factor VAX1 leads to induction of a second pituitary［J］.Development,2011，138(5)：873-878.
［43］RANGARAJU S，CHI V，PENNINGTON MW，et al.Kv1.3 potassium channels as a therapeutic target in multiple sclerosis［J］.Expert Opin Ther Targets,2009，13(8)：909-924.
［44］BEETON C，WULFF H，STANDIFER NE，et al.Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases［J］.Proc Natl Acad Sci USA,2006，103(46)：17414-17419.
［45］KUNDU-RAYCHAUDHURI S，CHEN YJ，WULFF H，et al.Kv1.3 in psoriatic disease：PAP-1，a small molecule inhibitor of Kv1.3 is effective in the SCID mouse psoriasis-xenograft model［J］.J Autoimmun,2014，55：63-72.
［46］IORIO J，PETRONI G，DURANTI C，et al.Potassium and sodium channels and the Warburg effect：Biophysical regulation of cancer metabolism［J］.Bioelectricity,2019，1(3)：188-200.
［47］WU J，ZHONG D，WU X，et al.Voltage-gated potassium channel Kv1.3 is highly expressed in human osteosarcoma and promotes osteosarcoma growth［J］.Int J Mol Sci,2013，14(9)：19245-19256.
［48］HERNANDEZ-MEZA G，VON FELDEN J，GONZALEZ-KOZLOVA EE，et al.DNA methylation profiling of human hepatocarcinogenesis［J］.Hepatology,2021，74(1)：183-199.

Memo

Memo:
National Natural Science Foundation of China（No.82160639）;国家自然科学基金项目（编号:82160639）；内蒙古医科大学面上项目（编号:YKD2021MS001）
Last Update: 1900-01-01