Prognostic value and immune regulatory role of dynamin 1-like in lung adenocarcinoma

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Abstract

Background

Lung adenocarcinoma (LUAD) is the most common histological subtype of non-small cell lung cancer (NSCLC), with poor treatment outcomes worldwide. Dynamin-related protein 1 (DRP1), which is encoded by the dynamin 1-like ( DNM1L) gene, acts as a regulator of mitochondrial fission and plays crucial roles in tumor initiation and progression. However, the clinical value and immune regulation of DNM1L in LUAD have not been explored.

Methods

We comprehensively analyzed the expression of DNM1L in the LUAD cohort of the Human Protein Atlas (HPA) and the University of The ALabama at Birmingham CANcer data analysis Portal (UALCAN) databases. Kaplan-Meier plotter, in addition to the PrognoScan database, was used to estimate the correlation between DNM1L expression and survival outcome of LUAD patients. The association between the immune tumor microenvironment (TME) and DNM1L expression in LUAD was evaluated based on the Tumor IMmune Estimation Resource (TIMER)2.0 database. Finally, the functions of DNM1L were validated in vitro experiments, including reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot, wound healing assays, and transwell assays.

Results

DNM1L was overexpressed in LUAD compared to healthy control tissues and was regarded as an independent prognostic factor. Overexpression of DNM1L was significantly related to clinical variables and poor survival outcomes of LUAD patients. Moreover, DNM1L expression was positively associated with the expression of key genes involved in the regulation of immune cell subsets, including T helper (Th)2 cells, Th cells, B cells, CD8 T cells, dendritic cells, and mast cells. In contrast, DNM1L was negatively correlated with the infiltrating levels of myeloid dendritic cells and B cells. Furthermore, DNM1L may play a role in regulating immune cell infiltration and have prognostic value in LUAD patients. Finally, the in vitro experiments showed that increased DNM1L significantly promoted the proliferation and migration of LUAD cells.

Conclusions

This study suggested that DNM1L may play an important role in regulating the proliferation and migration of LUAD cells as well as the infiltration of tumor-related immune cells, which suggests DNM1L was a potential therapeutic target in LUAD. Further studies are however warranted to define its exact mechanism of action and potential therapeutic significance in LUAD patients.

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Most cited references 49

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Cancer statistics, 2022

Rebecca Siegel, Kimberly D Miller, Hannah Fuchs … (2022)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes. Incidence data (through 2018) were collected by the Surveillance, Epidemiology, and End Results program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2019) were collected by the National Center for Health Statistics. In 2022, 1,918,030 new cancer cases and 609,360 cancer deaths are projected to occur in the United States, including approximately 350 deaths per day from lung cancer, the leading cause of cancer death. Incidence during 2014 through 2018 continued a slow increase for female breast cancer (by 0.5% annually) and remained stable for prostate cancer, despite a 4% to 6% annual increase for advanced disease since 2011. Consequently, the proportion of prostate cancer diagnosed at a distant stage increased from 3.9% to 8.2% over the past decade. In contrast, lung cancer incidence continued to decline steeply for advanced disease while rates for localized-stage increased suddenly by 4.5% annually, contributing to gains both in the proportion of localized-stage diagnoses (from 17% in 2004 to 28% in 2018) and 3-year relative survival (from 21% to 31%). Mortality patterns reflect incidence trends, with declines accelerating for lung cancer, slowing for breast cancer, and stabilizing for prostate cancer. In summary, progress has stagnated for breast and prostate cancers but strengthened for lung cancer, coinciding with changes in medical practice related to cancer screening and/or treatment. More targeted cancer control interventions and investment in improved early detection and treatment would facilitate reductions in cancer mortality.

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GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses

Zefang Tang, Chenwei Li, Boxi Kang … (2017)

Abstract Tremendous amount of RNA sequencing data have been produced by large consortium projects such as TCGA and GTEx, creating new opportunities for data mining and deeper understanding of gene functions. While certain existing web servers are valuable and widely used, many expression analysis functions needed by experimental biologists are still not adequately addressed by these tools. We introduce GEPIA (Gene Expression Profiling Interactive Analysis), a web-based tool to deliver fast and customizable functionalities based on TCGA and GTEx data. GEPIA provides key interactive and customizable functions including differential expression analysis, profiling plotting, correlation analysis, patient survival analysis, similar gene detection and dimensionality reduction analysis. The comprehensive expression analyses with simple clicking through GEPIA greatly facilitate data mining in wide research areas, scientific discussion and the therapeutic discovery process. GEPIA fills in the gap between cancer genomics big data and the delivery of integrated information to end users, thus helping unleash the value of the current data resources. GEPIA is available at http://gepia.cancer-pku.cn/.

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TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells.

Taiwen Li, Jingyu Fan, Binbin Wang … (2017)

Recent clinical successes of cancer immunotherapy necessitate the investigation of the interaction between malignant cells and the host immune system. However, elucidation of complex tumor-immune interactions presents major computational and experimental challenges. Here, we present Tumor Immune Estimation Resource (TIMER; cistrome.shinyapps.io/timer) to comprehensively investigate molecular characterization of tumor-immune interactions. Levels of six tumor-infiltrating immune subsets are precalculated for 10,897 tumors from 32 cancer types. TIMER provides 6 major analytic modules that allow users to interactively explore the associations between immune infiltrates and a wide spectrum of factors, including gene expression, clinical outcomes, somatic mutations, and somatic copy number alterations. TIMER provides a user-friendly web interface for dynamic analysis and visualization of these associations, which will be of broad utilities to cancer researchers. Cancer Res; 77(21); e108-10. ©2017 AACR.

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Author and article information

Journal

Journal ID (nlm-ta): Transl Lung Cancer Res

Journal ID (iso-abbrev): Transl Lung Cancer Res

Journal ID (publisher-id): TLCR

Title: Translational Lung Cancer Research

Publisher: AME Publishing Company

ISSN (Print): 2218-6751

ISSN (Electronic): 2226-4477

Publication date (Electronic): 06 December 2023

Publication date (Print): 26 December 2023

Volume: 12

Issue: 12

Pages: 2476-2493

Affiliations

[1 ]deptDepartment of Pharmacy , the Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital , Zhengzhou, China;

[2 ]deptHenan Engineering Research Center for Tumor Precision Medicine and Comprehensive Evaluation , Henan Cancer Hospital , Zhengzhou, China;

[3 ]deptHenan Provincial Key Laboratory of Anticancer Drug Research , Henan Cancer Hospital , Zhengzhou, China;

[4 ]deptDepartment of Internal Medicine , the Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital , Zhengzhou, China;

[5 ]deptDepartment of Respiratory and Critical Care Medicine , Henan Provincial Chest Hospital , Zhengzhou, China;

[6 ]deptThoracic Oncology Research Group, School of Medicine, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences , St. James’s Hospital and Trinity College Dublin , Dublin, Ireland;

[7 ]deptDepartment of Thoracic Surgery , Clínica Universidad de Navarra , Madrid, Spain;

[8 ]Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Jeonnam , Republic of Korea

Author notes

Contributions: (I) Conception and design: D Li, W Song, X Wu; (II) Administrative support: D Li, W Song; (III) Provision of study materials or patients: X Wu; (IV) Collection and assembly of data: X Wu; (V) Data analysis and interpretation: X Wu; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

[#]

These authors contributed equally to this work.

Correspondence to: Ding Li, PhD. Department of Pharmacy, the Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, No. 127 Dong Ming Road, Zhengzhou 450008, China; Henan Engineering Research Center for Tumor Precision Medicine and Comprehensive Evaluation, Henan Cancer Hospital, Zhengzhou, China; Henan Provincial Key Laboratory of Anticancer Drug Research, Henan Cancer Hospital, Zhengzhou, China. Email: ld_sunshinev@ 123456163.com .

[^]

ORCID: 0000-0001-8539-6611.

Article

Publisher ID: tlcr-12-12-2476

DOI: 10.21037/tlcr-23-685

PMC ID: 10775004

SO-VID: cd9942f9-691d-4737-978a-f4f63626d9f0

License:

Open Access Statement: 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.

History

Date received : 24 October 2023

Date accepted : 29 November 2023

Funding

Funded by: the Henan Provincial Science and Technology Research Project

Award ID: No. 232102311016

Funded by: the National Natural Science Foundation of China

Award ID: No. 82104204

Award ID: No. SBGJ202303018

Prognostic value and immune regulatory role of dynamin 1-like in lung adenocarcinoma

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Abstract

Background

Methods

Results

Conclusions

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Most cited references 49

Cancer statistics, 2022

GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses

TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells.

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