Expression and relationship with immunity of LRFN4 in lung adenocarcinoma: Based on bioinformatics analysis

Leucine rich repeat and fibronectin type III domain containing 4(LRFN4) has been reported to be upregulated in multiple tumors and related to prognosis and survival of patients. However, the function of LRFN4 in LUAD is still unclear. Herein, bioinformatic approach was used for the first time to elucidate the relationship between LRFN4 and LUAD. In LUAD tissues, we discovered that LRFN4 mRNA expression was considerably higher. Higher LRFN4 expression was associated with poorer prognosis and higher clinical stage of LUAD patients. Paraffin pathology sections (12 samples including LUAD tissues and paired normal tissues from the Second Affiliated Hospital of Chongqing Medical University) were used to verify the expression of LRFN4 at the protein level by immunohistochemical staining. On the other hand, we identified that LRFN4 expression was related to multiple immune cells that constitute tumor immune microenvironment. Pathway enrichment analysis also suggested the enrichment of several tumor- and immune-related pathways, such as: Hippo pathway, NOD-like pathway, TNF pathway and P53 pathway. Finally, we constructed an 8-gene prognostic risk signature based on 35 LRFN4-related immunomodulators using the Cox regression model, and obtained reasonably good accuracy through Receiver Operating Characteristic curve (ROC curve) validation. The risk signature was further identified as an independent risk factor – was linked with worse survival of LUAD patients. Furthermore, a prognostic risk profile based on LRFN4-related immunomodulators was constructed. Meanwhile, other clinical features were integrated together as prognostic markers to construct a nomogram to predict the long-term survival probability of LUAD patients, and fairly high credibility was obtained by validation of calibration curves. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study was funded by the General Project of Chongqing Natural Science Foundation in China: No. CSTB2022NSCQ-MSX1005 (Haitao Gu), the General Project of Chongqing Natural Science Foundation, Chongqing Science and Technology Commission, China: No. cstc2021jcyj- msxmX0153 (Linglong Peng) and the General Project of Chongqing Natural Science Foundation, Chongqing Science and Technology Commission, China: No. cstc2021jcyj-msxmX0112 (Yaxu Wang). Funding was mainly used for immunohistochemical staining of specimens and data analysis. Other than this, the work was not supported by any third party. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Not Applicable The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocol was approved by the ethics review board of Chongqing Bishan District People's Hospital (approval number 2022-KY-13) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Not Applicable I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Not Applicable I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Not Applicable Date Availability Statement Raw data analyzed in this study was from a public database: TCGA database (https://portal.gdc.cancer.gov/), codes and figures for this study are available from GitHub at https://github.com/Kaifeng306187/Zhiyong-Zhu.