nach oben

Journal of Cancer Research and Clinical Oncology

Erschienen in:

01.08.2019 | Original Article – Cancer Research

Protein expression of close homologue of L1 (CHL1) is a marker for overall survival in non-small cell lung cancer (NSCLC)

verfasst von: Jenny Hötzel, Nathaniel Melling, Julia Müller, Adam Polonski, Gerrit Wolters-Eisfeld, Jakob R. Izbicki, Karl-F. Karstens, Michael Tachezy

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 9/2019

Einloggen, um Zugang zu erhalten

Abstract

Background

The cell adhesion molecule close homologue of L1 (CHL1) is a potential tumour suppressor and was recently detected in non-small cell lung cancer (NSCLC) specimens. The expression pattern, prognostic, and functional role of CHL1 in NSCLCs is unknown.

Methods

We evaluated the protein expression of CHL1 by immunohistochemistry in 2161 NSCLC patients based on a tissue microarray. The results were correlated with clinical, histopathological, and patient survival data (Chi square test, t test, and log-rank test, respectively). A multivariate analysis (Cox regression) was performed to validate its impact on patients’ survival.

Results

CHL1 was expressed in NSCLC patients and was significantly overexpressed in lung adenocarcinomas and squamous cell carcinomas compared to neuroendocrine and large cell carcinomas of the lung (p < 0.001). CHL1 expression was associated with the T stage in adenocarcinomas (p = 0.011) and with metastatic lymph node status and UICC stage in squamous cell carcinomas (p = 0.034 and p = 0.035, respectively). Increased CHL1 expression was associated with improved survival in univariate (p = 0.031) and multivariate analyses (odds ratio 0.797, 95% confidence interval 0.677–0.939, p = 0.007).

Conclusion

The prognostic significance of CHL1 makes it a potential prognostic and therapeutic target and underlines its role as a tumour suppressor. Further validation studies and functional analyses are needed to investigate its potential role in tumourigenesis and dissemination.

Nur mit Berechtigung zugänglich

Browse the SEER Cancer Statistics Review 1975–2015 [Internet]. SEER. [cited 2019 Apr 5]. https://seer.cancer.gov/csr/1975_2015/browse_csr.php?sectionSEL=15&pageSEL=sect_15_table.01

Conacci-Sorrell ME, Ben-Yedidia T, Shtutman M, Feinstein E, Einat P, Ben-Ze’ev A (2002) Nr-CAM is a target gene of the beta-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis. Genes Dev. 16(16):2058–2072CrossRefPubMedPubMedCentral

Dancau A-M, Simon R, Mirlacher M, Sauter G (2016) Tissue microarrays. Methods Mol Biol Clifton NJ. 1381:53–65CrossRef

Frints SGM, Marynen P, Hartmann D, Fryns J-P, Steyaert J, Schachner M et al (2003) CALL interrupted in a patient with non-specific mental retardation: gene dosage-dependent alteration of murine brain development and behavior. Hum Mol Genet 12(13):1463–1474CrossRefPubMed

Górka B, Skubis-Zegadło J, Mikula M, Bardadin K, Paliczka E, Czarnocka B (2007) NrCAM, a neuronal system cell-adhesion molecule, is induced in papillary thyroid carcinomas. Br J Cancer 97(4):531–538CrossRefPubMedPubMedCentral

He L-H, Ma Q, Shi Y-H, Ge J, Zhao H-M, Li S-F et al (2013) CHL1 is involved in human breast tumorigenesis and progression. Biochem Biophys Res Commun 438(2):433–438CrossRefPubMed

Klat J, Mladenka A, Dvorackova J, Bajsova S, Simetka O (2019) L1CAM as a negative prognostic factor in endometrioid endometrial adenocarcinoma FIGO stage IA-IB. Anticancer Res 39(1):421–424CrossRefPubMed

Kotani N, Ida Y, Nakano T, Sato I, Kuwahara R, Yamaguchi A et al (2018) Tumor-dependent secretion of close homolog of L1 results in elevation of its circulating level in mouse model for human lung tumor. Biochem Biophys Res Commun. 501(4):982–987CrossRefPubMed

Lo Russo G, Imbimbo M, Corrao G, Proto C, Signorelli D, Vitali M et al (2017) Concomitant EML4-ALK rearrangement and EGFR mutation in non-small cell lung cancer patients: a literature review of 100 cases. Oncotarget. 8(35):59889–59900CrossRefPubMedPubMedCentral

Martín-Sánchez E, Mendaza S, Ulazia-Garmendia A, Monreal-Santesteban I, Blanco-Luquin I, Córdoba A et al (2017) CHL1 hypermethylation as a potential biomarker of poor prognosis in breast cancer. Oncotarget. 8(9):15789–15801CrossRefPubMedPubMedCentral

Naus S, Richter M, Wildeboer D, Moss M, Schachner M, Bartsch JW (2004) Ectodomain shedding of the neural recognition molecule CHL1 by the metalloprotease-disintegrin ADAM8 promotes neurite outgrowth and suppresses neuronal cell death. J Biol Chem 279(16):16083–16090CrossRefPubMed

Ognibene M, Pagnan G, Marimpietri D, Cangelosi D, Cilli M, Benedetti MC et al (2018) CHL1 gene acts as a tumor suppressor in human neuroblastoma. Oncotarget. 9(40):25903–25921CrossRefPubMedPubMedCentral

Raveh S, Gavert N, Ben-Ze’ev A (2009) L1 cell adhesion molecule (L1CAM) in invasive tumors. Cancer Lett. 282(2):137–145CrossRefPubMed

Reck M, Popat S, Reinmuth N, De Ruysscher D, Kerr KM, Peters S et al (2014) Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol Off J Eur Soc Med Oncol. 25(Suppl 3):iii27–iii39CrossRef

Ross DT, Scherf U, Eisen MB, Perou CM, Rees C, Spellman P et al (2000) Systematic variation in gene expression patterns in human cancer cell lines. Nat Genet 24(3):227–235CrossRefPubMed

Sakurai K, Migita O, Toru M, Arinami T (2002) An association between a missense polymorphism in the close homologue of L1 (CHL1, CALL) gene and schizophrenia. Mol Psychiatry. 7(4):412–415CrossRefPubMed

Senchenko VN, Krasnov GS, Dmitriev AA, Kudryavtseva AV, Anedchenko EA, Braga EA et al (2011) Differential expression of CHL1 gene during development of major human cancers. PLoS One 6(3):e15612CrossRefPubMedPubMedCentral

Shen M, Ren X (2017) Highlights on immune checkpoint inhibitors in non-small cell lung cancer. Tumour Biol J Int Soc Oncodevelopmental Biol Med. 39(3):1010428317695013CrossRef

Siesser PF, Maness PF (2009) L1 cell adhesion molecules as regulators of tumor cell invasiveness. Cell Adhes Migr. 3(3):275–277CrossRef

Simon R, Mirlacher M, Sauter G (2010) Immunohistochemical analysis of tissue microarrays. Methods Mol Biol Clifton NJ. 664:113–126CrossRef

Tachezy M, Zander H, Marx AH, Gebauer F, Rawnaq T, Kaifi JT et al (2011) ALCAM (CD166) expression as novel prognostic biomarker for pancreatic neuroendocrine tumor patients. J Surg Res 170(2):226–232CrossRefPubMed

Tang H, Jiang L, Zhu C, Liu R, Wu Y, Yan Q et al (2019) Loss of cell adhesion molecule L1 like promotes tumor growth and metastasis in esophageal squamous cell carcinoma. Oncogene 8:1CrossRef

Tian W, Li X, Ren Y, Yin Z, Quan X, Zheng C et al (2018) CHL1 gene polymorphisms increase lung cancer susceptibility. Oncotarget. 9(17):13545–13550CrossRefPubMedPubMedCentral

Wei MH, Karavanova I, Ivanov SV, Popescu NC, Keck CL, Pack S et al (1998) In silico-initiated cloning and molecular characterization of a novel human member of the L1 gene family of neural cell adhesion molecules. Hum Genet 103(3):355–364CrossRefPubMed

Went P, Vasei M, Bubendorf L, Terracciano L, Tornillo L, Riede U et al (2006) Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers. Br J Cancer 94(1):128–135CrossRefPubMedPubMedCentral

Yu W, Zhu K, Wang Y, Yu H, Guo J. Overexpression of miR-21-5p promotes proliferation and invasion of colon adenocarcinoma cells through targeting CHL1. Mol Med [Internet]. 2018 Jul 16 [cited 2019 Mar 18];24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048725/

Zamay TN, Zamay GS, Kolovskaya OS, Zukov RA, Petrova MM, Gargaun A et al (2017) Current and prospective protein biomarkers of lung cancer. Cancers. 9(11):155CrossRefPubMedCentral

Zecchini S, Cavallaro U (2010) Neural cell adhesion molecule in cancer: expression and mechanisms. Adv Exp Med Biol 663:319–333CrossRefPubMed

Titel: Protein expression of close homologue of L1 (CHL1) is a marker for overall survival in non-small cell lung cancer (NSCLC)
verfasst von: Jenny Hötzel
Nathaniel Melling
Julia Müller
Adam Polonski
Gerrit Wolters-Eisfeld
Jakob R. Izbicki
Karl-F. Karstens
Michael Tachezy
Publikationsdatum: 01.08.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 9/2019
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-019-02989-x

Neu im Fachgebiet Onkologie

16.04.2024 | Maligne primäre ZNS-Tumoren | Nachrichten

Springer Medizin

Protein expression of close homologue of L1 (CHL1) is a marker for overall survival in non-small cell lung cancer (NSCLC)

Abstract

Background

Methods

Results

Conclusion

Neu im Fachgebiet Onkologie

Manche Gestagene können das Risiko für Meningeome erhöhen

Einladung zum PSA-Screening senkt die Krebssterblichkeit

Chemotherapie mit Hindernissen

Das Ende der vollständigen axillären Lymphknotendissektion

Update Onkologie

Springer Medizin

Abstract

Background

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 9/2019

Synchronicity of genetic variants between primary sites and metastatic lymph nodes, and prognostic impact in nodal metastatic lung adenocarcinoma

Effects of surgery on survival of elderly patients with stage I small-cell lung cancer: analysis of the SEER database

The vulvar immunohistochemical panel (VIP) project: molecular profiles of vulvar Paget’s disease

Impacts of thoracoscopic surgery and high grade histologic subtypes on spread through air spaces in small stage I lung adenocarcinomas

Selective radiofrequency ablation of tumor by magnetically targeting of multifunctional iron oxide–gold nanohybrid

A comparison of regorafenib and fruquintinib for metastatic colorectal cancer: a systematic review and network meta-analysis

Neu im Fachgebiet Onkologie

Manche Gestagene können das Risiko für Meningeome erhöhen

Einladung zum PSA-Screening senkt die Krebssterblichkeit

Chemotherapie mit Hindernissen

Das Ende der vollständigen axillären Lymphknotendissektion

Update Onkologie