# Investigation of biomarkers and associated molecular mechanism shared between colorectal cancer and lung adenocarcinoma

## TL;DR

This study identifies five shared biomarkers between colorectal cancer and lung adenocarcinoma, offering potential targets for diagnosis and treatment.

## Contribution

The study discovers five novel shared biomarkers and their molecular mechanisms in colorectal cancer and lung adenocarcinoma.

## Key findings

- Five hub genes (HSPA6, NOTCH3, PKP2, SMAD9, GPD1L) were identified as shared biomarkers between CRC and LUAD.
- HSPA6 and SMAD9 are linked to protein binding functions in cancer progression.
- NOTCH3 showed high functional similarity and a strong correlation with Natural Killer cells.

## Abstract

The relationship between colorectal cancer (CRC) and lung adenocarcinoma (LUAD) has been acknowledged in recent years, yet the biomarkers and mechanisms underlying their interaction remain unclear. This study aimed to explore the genetic characteristics and molecular mechanisms shared by CRC and LUAD.

To identify common differentially expressed genes (co-DEGs) between tumor and normal samples, we analyzed gene expression datasets for CRC and LUAD from the GEO and TCGA databases. Then, co-DEGs were further analyzed for enrichment. The survival analysis and protein-protein interaction (PPI) analysis were used to explored biomarkers for two diseases. Based on the identified biomarkers, the functional similarity, immune cell infiltration, and Gene Set Enrichment Analyses (GSEA) were performed. Moreover, the drug-gene interaction was predicted based on biomarkers. Finally, the qRT-PCR, Western blotting, and enzyme-linked immunosorbent assay (ELISA) to validate the expression of these biomarkers in CRC and LUAD based on cell lines and mice model.

We explored totally 3470 co-DEGs of tumor vs. normal based on CRC and LUAD dataset. K-M survival and PPI network analysis revealed five hub prognostic genes, including HSPA6, NOTCH3, PKP2, SMAD9, and GPD1L, as biomarkers for two diseases, with enrichment analysis showing that biomarkers like HSPA6 and SMAD9 were primarily associated with protein binding functions. Functional similarity analysis revealed that the five biomarkers exhibited a high degree of similarity in their biological roles, with NOTCH3 showing the highest similarity, further supported by immune infiltration analysis indicating a significant and strong positive correlation between NOTCH3 and Natural Killer cells. Finally, the expression investigation of five biomarkers based on cell lines and mice model validated the results of bioinformatics analysis.

HSPA6, NOTCH3, PKP2, SMAD9, and GPD1L were five novel biomarkers for CRC and LUAD clinical diagnosis or treatment. HSPA6 and SMAD9 might take part in the progression of CRC and LUAD via protein binding function.

The online version contains supplementary material available at 10.1007/s12672-025-03240-5.