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Kreus MA, Lehtonen ST, Mäkinen JM, Lappi-Blanco HE, Laitakari KEM, Johnson SA, Hinttala RML, Kaarteenaho RL. High NHLRC2 expression is associated with shortened survival in lung adenocarcinoma. Transl Lung Cancer Res 2023;12(6):1221-1235. doi: 10.21037/tlcr-22-815

High NHLRC2 expression is associated with shortened survival in lung adenocarcinoma

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Author: Kreus, Mervi A.1,2; Lehtonen, Siri T.3,4; Mäkinen, Johanna M.5,6;
Organizations: 1Research Unit of Biomedicine and Internal Medicine, University of Oulu, Oulu, Finland
2Center of Internal Medicine and Respiratory Medicine, Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland
3Department of Obstetrics and Gynecology and Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland
4Medical Research Center Oulu and Research Unit of Clinical Medicine, Oulu University Hospital and University of Oulu, Oulu, Finland
5Department of Pathology, Oulu University Hospital, Oulu, Finland
6Department of Pathology, Research Unit of Translational Medicine, University of Oulu, Oulu, Finland
7Department of Surgery, Division of Gastroenterology, Oulu University Hospital, Oulu, Finland
8Medical Research Center Oulu, Research Unit of Translational Medicine, University of Oulu, Oulu, Finland
9Biocenter Oulu, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe20230912122845
Language: English
Published: AME Publishing Company, 2023
Publish Date: 2023-09-12
Description:

Abstract

Background: Certain variants of NHL repeat (named after NCL-1, HT2A and LIN-41)-containing protein 2 (NHLRC2) gene have been linked to severe fibrotic interstitial lung disease in children. The aim of the current study was to evaluate the expression of NHLRC2 in lung cell and tissue samples from patients with lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC).

Methods: The expression of NHLRC2 in lung tissue samples was studied by immunohistochemistry (102 ADC, 111 SCC), mRNA in situ hybridization (4 ADC, 3 SCC), and Western blot analysis (3 ADC, 2 SCC). The immunohistochemical NHLRC2 expression was measured by image analysis software and the percentage of NHLRC2-positive cancer cells was evaluated by semiquantitative analysis. The immunohistochemical results of NHLRC2 were compared with the clinical and histological characteristics of the patients. NHLRC2 protein levels in primary stromal and epithelial lung cancer cell lines were measured by Western blot analysis.

Results: NHLRC2 was mainly expressed in cancer cells and inflammatory cells within the tumor. The NHLRC2 expression evaluated by image analysis method was significantly higher in ADC compared with that in SCC (P<0.001). High NHLRC2 expression was associated with reduced disease specific survival (P=0.002), overall survival (P=0.001), and high mitotic activity (P=0.042) in ADC. Additionally, the proportion of NHLRC2-positive cancer cells analyzed by the semiquantitative method was significantly higher in ADC than in SCC (P<0.001).

Conclusions: NHLRC2 expression was higher in lung ADC than in SCC and its expression was associated with poor survival in ADC patients. Further studies are required to clarify the pathogenetic role of NHLRC2 in lung cancer.

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Series: Translational lung cancer research
ISSN: 2218-6751
ISSN-E: 2226-4477
ISSN-L: 2218-6751
Volume: 12
Issue: 6
Pages: 1221 - 1235
DOI: 10.21037/tlcr-22-815
OADOI: https://oadoi.org/10.21037/tlcr-22-815
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Subjects:
NHL-repeat containing protein 2
adenocarcinoma
non-small cell lung cancer
squamous cell carcinoma
Article
Funding: This work was supported by the Foundation of the Finnish Anti-Tuberculosis Association (to MAK, and to RLK), the Tampere Tuberculosis foundation (to MAK), Väinö and Laina Kivi Foundation (to MAK), the Research Foundation of the Pulmonary Diseases (to MAK, and to RLK), Orion research foundation (to MAK), Medical Research Center Oulu (to STL), Academy of Finland profiling program (Decision No. 311934, to RMLH), University of Oulu (to RMLH), the Foundation for Pediatric Research, Finland (to RMLH), the Jalmari and Rauha Ahokas Foundation (to RLK), the Research Foundation of the North Finland (to RLK), and the state subsidy of Oulu University Hospital (to RLK). Funding sources were not involved in study design, collection, analysis and interpretation of data, writing of the report, or decision to submit the article for publication.
Copyright information: © Translational Lung Cancer Research. All rights reserved. This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non- commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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