结直肠癌和肺腺癌之间共享的生物标志物及相关分子机制的研究。

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

作者信息

Gao Kun, Yu Lianyang, Wang Lei, Gao Linlu, Li Tingting, Sun Jing

机构信息

Department of Oncology, Zibo integrated Chinese and Western medicine hospital, ZiBo City, 255000, Shandong Province, China.

Department of Pulmonary Diseases, Zibo integrated Chinese and Western medicine hospital, ZiBo City, 255000, Shandong Province, China.

出版信息

Discov Oncol. 2025 Aug 12;16(1):1540. doi: 10.1007/s12672-025-03240-5.

DOI:10.1007/s12672-025-03240-5

PMID:40796704

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

近年来，结直肠癌（CRC）与肺腺癌（LUAD）之间的关系已得到认可，但它们相互作用的生物标志物和机制仍不清楚。本研究旨在探索CRC和LUAD共有的遗传特征和分子机制。

方法

为了鉴定肿瘤样本与正常样本之间的共同差异表达基因（co-DEGs），我们分析了来自GEO和TCGA数据库的CRC和LUAD基因表达数据集。然后，对co-DEGs进行进一步的富集分析。生存分析和蛋白质-蛋白质相互作用（PPI）分析用于探索这两种疾病的生物标志物。基于鉴定出的生物标志物，进行功能相似性、免疫细胞浸润和基因集富集分析（GSEA）。此外，基于生物标志物预测药物-基因相互作用。最后，通过qRT-PCR、蛋白质印迹和酶联免疫吸附测定（ELISA），基于细胞系和小鼠模型验证这些生物标志物在CRC和LUAD中的表达。

结果

基于CRC和LUAD数据集，我们共探索到3470个肿瘤与正常样本的co-DEGs。K-M生存分析和PPI网络分析揭示了五个枢纽预后基因，包括HSPA6、NOTCH3、PKP2、SMAD9和GPD1L，作为这两种疾病的生物标志物，富集分析表明，像HSPA6和SMAD9这样的生物标志物主要与蛋白质结合功能相关。功能相似性分析表明，这五个生物标志物在生物学作用上表现出高度相似性，其中NOTCH3的相似性最高，免疫浸润分析进一步支持了这一点，表明NOTCH3与自然杀伤细胞之间存在显著且强烈的正相关。最后，基于细胞系和小鼠模型对五个生物标志物的表达研究验证了生物信息学分析的结果。