Comprehensive pan-cancer analysis of CHRDL1 and experimental validation of its role in lung adenocarcinoma

Our plain-English summary of Comprehensive pan-cancer analysis of CHRDL1 and experimental validation of its role in lung adenocarcinoma, by G. Ou, T. Gao, S. Hu, et al (BMC Cancer, 2025).

The study

• Authors: G. Ou, T. Gao, S. Hu, S. Zhang, S. Song, Y. Sun, Y. Wang, R. Zhong, K. Hu, L. Gao, M. Jiang
• Journal: BMC Cancer
• Published: 2025;25(1):783
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Chordin-like 1 (CHRDL1) is a secreted antagonist of bone morphogenetic proteins, and has been implicated in various biological processes and cancer prognosis. This study offered a detailed examination of CHRDL1 expression across 33 diverse cancer types, leveraging data from The Cancer Genome Atlas (TCGA) and supplementary public datasets. We demonstrated that, for the majority of cancer types, CHRDL1 expression was reduced in tumor tissues compared to normal adjacent tissues. Notably, lower CHRDL1 expression led to negative prognosis in malignancies such as lung adenocarcinoma (LUAD), melanoma (SKCM), and mesothelioma (MESO). Furthermore, CHRDL1 expression was positively correlated with the infiltration of CD4⁺ T cells, CD8⁺ T cells, B cells, neutrophils, macrophages, and dendritic cells in most tumors. Higher CHRDL1 expression correlated with more favorable immune profiles and a reduction in tumor stemness. To assess the effect of CHRDL1 overexpression on LUAD progression, we conducted CCK-8, wound healing, and invasion assays in vitro, along with subcutaneous tumor formation experiments in nude mice. The results showed that the proliferation, migration, and invasion abilities of A549 and H1299 cells with high CHRDL1 expression were reduced, and the growth of A549 cells was also significantly inhibited in nude mice. These findings underscored CHRDL1's potential as a prognostic biomarker and its influence on tumor immunology and cellular dynamics.

© 2025. The Author(s).

In plain English

This study analysed a gene called CHRDL1 across 33 cancer types using public databases, including The Cancer Genome Atlas, and then tested it in lung adenocarcinoma cells and mice. It did not study asbestos or any other exposure. The authors reported low CHRDL1 expression in most cancerous tissues. Low expression was associated with poorer prognosis in lung adenocarcinoma, skin melanoma and mesothelioma, but with better prognosis in five other cancers, including stomach and liver cancer. The article does not say which type of mesothelioma was included. Its text gives hazard ratios only as above or below 1, without numerical estimates. Higher CHRDL1 expression was positively correlated with immune cell infiltration in most tumors. The authors made two lung adenocarcinoma cell lines (A549 and H1299) produce extra CHRDL1. These cells grew, migrated and invaded less. In nude mice, tumors grown from the altered A549 cells had lower volume and weight than those in the control group. The authors concluded that high CHRDL1 expression inhibited lung adenocarcinoma cell proliferation and metastasis. They noted that the database analyses lacked detailed patient-specific data, the mouse experiment was small, and the mechanisms remain unclear.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Bioinformatic analysis of public cancer databases (pan-cancer), combined with laboratory cell-line experiments and a mouse tumor-transplant experiment
• Who was studied: Tumor and normal tissue data for 33 cancer types from TCGA, supplemented with GTEx normal samples (sample counts not given in the text). The cancers included mesothelioma, labelled MESO, with no type specified. The laboratory work used lung adenocarcinoma cell lines A549 and H1299, and twelve 5-week-old BALB/c nude mice.
• Exposure: No asbestos or fiber exposure was studied. The factor examined was CHRDL1 gene expression level in database samples, and experimental overexpression of CHRDL1 in lung adenocarcinoma cells using lentiviral vectors.
• Main results:
  • CHRDL1 expression was low in most cancerous tissues compared with normal tissues
  • Low CHRDL1 expression was associated with poor prognosis in lung adenocarcinoma (LUAD), skin melanoma (SKCM) and mesothelioma (MESO), reported as HR less than 1 with p less than 0.05. It was associated with improved prognosis in BLCA, LIHC, KIRC, LUSC and STAD, reported as HR greater than 1 with p less than 0.05. The text gives no numerical hazard-ratio estimates or confidence intervals; the analysis is shown in a forest plot (Fig. 3A).
  • The cancers with the highest CHRDL1 mutation rates were SKCM (4.95%), UCEC (4.54%), STAD (3.41%), LUAD (3.36%), LUSC (3.08%) and CRC (2.86%)
  • CHRDL1 expression was positively correlated with immune cell infiltration in most tumors
  • In BLCA, BRCA, COAD, ESCA, HNSC, LUAD, LUSC, PAAD, STAD and TGCT, higher CHRDL1 expression was associated with a lower tumor stemness index
  • In A549 and H1299 lung adenocarcinoma cells, CHRDL1 overexpression significantly inhibited proliferation, migration and invasion
  • In nude mice, tumor volume and weight were significantly lower with CHRDL1-overexpressing A549 cells than in the control group
• The authors' conclusion: The authors concluded that high CHRDL1 expression inhibited the proliferation and metastasis of lung adenocarcinoma cells
• Limitations the authors state:
  • The findings rest on bioinformatic analyses of public databases, which lack detailed, patient-specific data
  • The mouse tumor-transplant experiment used a relatively small sample size
  • The nude mouse model cannot fully replicate the immune environment of human tumors
  • Protein expression data for CHRDL1 in tumor tissues were scarce or absent
  • The mechanisms linking CHRDL1 to immune cell infiltration remain unclear

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Adenocarcinoma, Prognosis, Mesothelioma, Macrophage, A549 Cells, Biomarker.

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