Lamin B1: a novel biomarker in adult and pediatric adrenocortical carcinoma

in Endocrine-Related Cancer
Authors:
Yihao Chen Department of Andrology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China
Department of Urology, Huizhou Municipal Central Hospital, Huizhou, Guangdong, China

Search for other papers by Yihao Chen in
Current site
Google Scholar
PubMed
Close
,
Jiahong Chen Department of Urology, Huizhou Municipal Central Hospital, Huizhou, Guangdong, China

Search for other papers by Jiahong Chen in
Current site
Google Scholar
PubMed
Close
,
Yongcheng Shi Department of Urology, Huizhou Municipal Central Hospital, Huizhou, Guangdong, China

Search for other papers by Yongcheng Shi in
Current site
Google Scholar
PubMed
Close
,
Xiaohui Ling Reproductive Medicine Center, Huizhou Municipal Central Hospital, Huizhou, Guangdong, China

Search for other papers by Xiaohui Ling in
Current site
Google Scholar
PubMed
Close
,
Shumin Fang Science Research Center, Huizhou Municipal Central Hospital, Huizhou, Guangdong, China

Search for other papers by Shumin Fang in
Current site
Google Scholar
PubMed
Close
,
Chuanfan Zhong Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China

Search for other papers by Chuanfan Zhong in
Current site
Google Scholar
PubMed
Close
,
Fengping Liu State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China

Search for other papers by Fengping Liu in
Current site
Google Scholar
PubMed
Close
,
Weide Zhong State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China
Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China
Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, Guangzhou, Guangdong

Search for other papers by Weide Zhong in
Current site
Google Scholar
PubMed
Close
,
Xuecheng Bi Department of Urology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China

Search for other papers by Xuecheng Bi in
Current site
Google Scholar
PubMed
Close
,
Zhong Dong Department of Urology, Huizhou Municipal Central Hospital, Huizhou, Guangdong, China

Search for other papers by Zhong Dong in
Current site
Google Scholar
PubMed
Close
, and
Jianming Lu Department of Andrology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China
Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China

Search for other papers by Jianming Lu in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0002-3794-641X

Correspondence should be addressed to Z Dong or J Lu: hzdongzhong@126.com or louiscfc8@gmail.com

*(Y Chen, J Chen and Y Shi contributed equally to this work)

Restricted access
Rent on DeepDyve

Sign up for journal news

Adrenocortical carcinoma (ACC) is a malignancy with a poor prognosis and high mortality rate. A high tumor mutational burden (TMB) has been found to be associated with poor prognosis in ACC. Thus, exploring ACC biomarkers based on TMB holds significant importance for patient risk stratification. In our research, we utilized weighted gene coexpression network analysis and an assay for transposase-accessible chromatin with high-throughput sequencing to identify genes associated with TMB. Through the comprehensive analysis of various public datasets, Lamin B1 (LMNB1) was identified as a biomarker associated with a high TMB and low chromatin accessibility. Immunohistochemical staining demonstrated high expression of LMNB1 in ACC compared to noncancerous tissues. Functional enrichment analyses revealed that the function of LMNB1 is associated with cell proliferation and division. Furthermore, cell assays suggested that LMNB1 promotes tumor proliferation and invasion. In addition, mutation analysis suggested that the high expression of LMNB1 is associated with TP53 mutations. Additionally, LMNB1 was highly expressed in the vast majority of solid tumors across cancers. In our immune analysis, we discovered that the high expression of LMNB1 might suppress the infiltration of CD8+ T cells in the ACC microenvironment. In summary, LMNB1 is a predictive factor for the poor prognosis of adult and pediatric ACC. Its high expression in ACC is positively associated with high TMB and lower chromatin accessibility, and it promotes ACC cell proliferation and invasion. Therefore, LMNB1 holds promise as a novel biomarker and potential therapeutic target for ACC.

Supplementary Materials

 

  • Collapse
  • Expand
  • Blanche P, Dartigues JF & & Jacqmin-Gadda H 2013 Estimating and comparing time-dependent areas under receiver operating characteristic curves for censored event times with competing risks. Statistics in Medicine 32 53815397. (https://doi.org/10.1002/sim.5958)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Corces MR, Buenrostro JD, Wu B, Greenside PG, Chan SM, Koenig JL, Snyder MP, Pritchard JK, Kundaje A, Greenleaf WJ, et al.2016 Lineage-specific and single-cell chromatin accessibility charts human hematopoiesis and leukemia evolution. Nature Genetics 48 11931203. (https://doi.org/10.1038/ng.3646)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Corces MR, Granja JM, Shams S, Louie BH, Seoane JA, Zhou W, Silva TC, Groeneveld C, Wong CK, Cho SW, et al.2018 The chromatin accessibility landscape of primary human cancers. Science 362. (https://doi.org/10.1126/science.aav1898)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Curylova L, Ramos H, Saraiva L & & Skoda J 2022 Noncanonical roles of p53 in cancer stemness and their implications in sarcomas. Cancer Letters 525 131145. (https://doi.org/10.1016/j.canlet.2021.10.037)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Demeure MJ, Coan KE, Grant CS, Komorowski RA, Stephan E, Sinari S, Mount D & & Bussey KJ 2013 PTTG1 overexpression in adrenocortical cancer is associated with poor survival and represents a potential therapeutic target. Surgery 154 14051416. (https://doi.org/10.1016/j.surg.2013.06.058)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dittmer TA & & Misteli T 2011 The lamin protein family. Genome Biology 12 222. (https://doi.org/10.1186/gb-2011-12-5-222)

  • Else T, Kim AC, Sabolch A, Raymond VM, Kandathil A, Caoili EM, Jolly S, Miller BS, Giordano TJ & & Hammer GD 2014 Adrenocortical carcinoma. Endocrine Reviews 35 282326. (https://doi.org/10.1210/er.2013-1029)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Frankiw L & & Li G 2022 The tumor microenvironment's role in malignant progression and treatment response. Cancer Letters 548 215888. (https://doi.org/10.1016/j.canlet.2022.215888)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Giordano TJ, Kuick R, Else T, Gauger PG, Vinco M, Bauersfeld J, Sanders D, Thomas DG, Doherty G & & Hammer G 2009 Molecular classification and prognostication of adrenocortical tumors by transcriptome profiling. Clinical Cancer Research 15 668676. (https://doi.org/10.1158/1078-0432.CCR-08-1067)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Goldman MJ, Craft B, Hastie M, Repečka K, McDade F, Kamath A, Banerjee A, Luo Y, Rogers D, Brooks AN, et al.2020 Visualizing and interpreting cancer genomics data via the Xena platform. Nature Biotechnology 38 675678. (https://doi.org/10.1038/s41587-020-0546-8)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gu Z, Eils R & & Schlesner M 2016 Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics 32 28472849. (https://doi.org/10.1093/bioinformatics/btw313)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hanahan D 2022 Hallmarks of cancer: new dimensions. Cancer Discovery 12 3146. (https://doi.org/10.1158/2159-8290.CD-21-1059)

  • Izdebska M, Gagat M & & Grzanka A 2018 Overexpression of lamin B1 induces mitotic catastrophe in colon cancer LoVo cells and is associated with worse clinical outcomes. International Journal of Oncology 52 89102. (https://doi.org/10.3892/ijo.2017.4182)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jardim DL, Goodman A, de Melo Gagliato D & & Kurzrock R 2021 The challenges of tumor mutational burden as an immunotherapy biomarker. Cancer Cell 39 154173. (https://doi.org/10.1016/j.ccell.2020.10.001)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Landwehr LS, Schreiner J, Appenzeller S, Kircher S, Herterich S, Sbiera S, Fassnacht M, Kroiss M & & Weigand I 2021 A novel patient-derived cell line of adrenocortical carcinoma shows a pathogenic role of germline MUTYH mutation and high tumour mutational burden. European Journal of Endocrinology 184 823835. (https://doi.org/10.1530/EJE-20-1423)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Langfelder P & & Horvath S 2008 WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 9 559. (https://doi.org/10.1186/1471-2105-9-559)

  • Li J, Sun Z, Cui Y, Qin L, Wu F, Li Y, Du N & & Li X 2022 Knockdown of LMNB1 inhibits the proliferation of lung adenocarcinoma cells by inducing DNA damage and cell senescence. Frontiers in Oncology 12 913740. (https://doi.org/10.3389/fonc.2022.913740)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lu J, Dong W, He H, Han Z, Zhuo Y, Mo R, Liang Y, Zhu J, Li R, Qu H, et al.2018 Autophagy induced by overexpression of DCTPP1 promotes tumor progression and predicts poor clinical outcome in prostate cancer. International Journal of Biological Macromolecules 118 599609. (https://doi.org/10.1016/j.ijbiomac.2018.06.005)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Luo Y, Chen Q & & Lin J 2022 Identification and validation of a tumor mutation burden-related signature combined with immune microenvironment infiltration in adrenocortical carcinoma. Mathematical Biosciences and Engineering 19 70557075. (https://doi.org/10.3934/mbe.2022333)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mayakonda A, Lin DC, Assenov Y, Plass C & & Koeffler HP 2018 Maftools: efficient and comprehensive analysis of somatic variants in cancer. Genome Research 28 17471756. (https://doi.org/10.1101/gr.239244.118)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Olivier M, Hollstein M & & Hainaut P 2010 TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harbor Perspectives in Biology 2 a001008. (https://doi.org/10.1101/cshperspect.a001008)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Paschoalin VP, Tucci Júnior S, Estevanato AB, Tiraboschi R, Antonini SR, Muglia VF, Chahud F, Mermejo LM, de Bessa Júnior J & & Fernandes Molina CA 2022 Histopathological criteria for paediatric adrenocortical carcinoma. Hormone Research in Paediatrics 95 347353. (https://doi.org/10.1159/000524892)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pinto EM, Rodriguez-Galindo C, Choi JK, Pounds S, Liu Z, Neale G, Finkelstein D, Hicks JM, Pappo AS, Figueiredo BC, et al.2016 Prognostic significance of major histocompatibility complex Class II expression in pediatric adrenocortical tumors: ASt. Jude and Children's Oncology Group study. Clinical Cancer Research 22 62476255. (https://doi.org/10.1158/1078-0432.CCR-15-2738)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Shen W, Song Z, Zhong X, Huang M, Shen D, Gao P, Qian X, Wang M, He X, Wang T, et al.2022 Sangerbox: a comprehensive, interaction-friendly clinical bioinformatics analysis platform. iMeta 1 e36. (https://doi.org/10.1002/imt2.36)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Shumaker DK, Solimando L, Sengupta K, Shimi T, Adam SA, Grunwald A, Strelkov SV, Aebi U, Cardoso MC & & Goldman RD 2008 The highly conserved nuclear lamin Ig-fold binds to PCNA: its role in DNA replication. Journal of Cell Biology 181 269280. (https://doi.org/10.1083/jcb.200708155)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sun S, Xu MZ, Poon RT, Day PJ & & Luk JM 2010 Circulating Lamin B1 (LMNB1) biomarker detects early stages of liver cancer in patients. Journal of Proteome Research 9 7078. (https://doi.org/10.1021/pr9002118)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Terzolo M, Baudin AE, Ardito A, Kroiss M, Leboulleux S, Daffara F, Perotti P, Feelders RA, deVries JH, Zaggia B, et al.2013 Mitotane levels predict the outcome of patients with adrenocortical carcinoma treated adjuvantly following radical resection. European Journal of Endocrinology 169 263270. (https://doi.org/10.1530/EJE-13-0242)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wang J, Mi S, Ding M, Li X & & Yuan S 2022 Metabolism and polarization regulation of macrophages in the tumor microenvironment. Cancer Letters 543 215766. (https://doi.org/10.1016/j.canlet.2022.215766)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wu T, Hu E, Xu S, Chen M, Guo P, Dai Z, Feng T, Zhou L, Tang W, Zhan L, et al.2021 clusterProfiler 4.0: a universal enrichment tool for interpreting omics data. Innovation 2 100141. (https://doi.org/10.1016/j.xinn.2021.100141)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Xu F, Guan Y, Zhang P, Xue L, Ma Y, Gao M, Chong T & & Ren BC 2022 Tumor mutational burden presents limiting effects on predicting the efficacy of immune checkpoint inhibitors and prognostic assessment in adrenocortical carcinoma. BMC Endocrine Disorders 22 130. (https://doi.org/10.1186/s12902-022-01017-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yan F, Powell DR, Curtis DJ & & Wong NC 2020 From reads to insight: a hitchhiker's guide to ATAC-seq data analysis. Genome Biology 21 22. (https://doi.org/10.1186/s13059-020-1929-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yang Z, Sun Q, Guo J, Wang S, Song G, Liu W, Liu M & & Tang H 2019 GRSF1-mediated MIR-G-1 promotes malignant behavior and nuclear autophagy by directly upregulating TMED5 and LMNB1 in cervical cancer cells. Autophagy 15 668685. (https://doi.org/10.1080/15548627.2018.1539590)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zeng D, Ye Z, Shen R, Yu G, Wu J, Xiong Y, Zhou R, Qiu W, Huang N, Sun L, et al.2021 IOBR: multi-omics immuno-oncology biological research to decode tumor microenvironment and signatures. Frontiers in Immunology 12 687975. (https://doi.org/10.3389/fimmu.2021.687975)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zhong C, Long Z, Yang T, Wang S, Zhong W, Hu F, Teoh JY, Lu J & & Mao X 2023 M6A-modified circRBM33 promotes prostate cancer progression via PDHA1-mediated mitochondrial respiration regulation and presents a potential target for ARSI therapy. International Journal of Biological Sciences 19 15431563. (https://doi.org/10.7150/ijbs.77133)

    • PubMed
    • Search Google Scholar
    • Export Citation