Low LAMA2 expression may affect drug resistance and prognosis in ovarian cancer via positive LGR5 coexpression

Drug resistance often occurs during ovarian cancer (OC) treatment, and factors related to drug resistance often contribute to poor prognosis. Laminin subunit alpha 2 (LAMA2) can affect cancer progression, but its association with OC has rarely been studied. This study aimed to preliminarily investigate the expression of LAMA2 in OC and its ability to predict chemoresistance and patient prognosis using open-access big data and bioinformatics analysis.

Data retrieved from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression Project (GTEx), and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) were used to analyze messenger ribonucleic acid (mRNA) and protein expression. Protein expression in OC tissues was detected using hematoxylin-eosin (HE) and immunohistochemistry (IHC). Up to 10,000 samples from 33 different cancer types and bivariate correlations were used to investigate the coexpression of the two genes. Gene expression with respect to tumor immune infiltration was determined using the R software package and TCGA data.

Likely modified by deoxyribonucleic acid (DNA) methylation, LAMA2 expression was significantly downregulated at the mRNA and protein levels in OC tissues and was consistently downregulated in 19 different tumors. Furthermore, LAMA2 expression was decreased in 90 platinum-resistant and cisplatin-resistant A2780 cells. A low level of LAMA2 predicted short overall survival (OS) and disease-free survival (DFS) in 149 OC patients and was related to low immune infiltration and high tumor grade. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the genes coexpressed with LAMA2 revealed that Rat sarcoma (Ras) protein signaling and other oncogene-related pathways were involved. LAMA2 was positively coexpressed with leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), aldehyde dehydrogenase 1 family member A1 (ALDH1A1), and von Willebrand factor (VWF) in 558 OC and 90 drug-resistant tissues and was coexpressed with these three genes in 19, 17, and 25 different tumors, respectively. Moreover, low LGR5 expression predicted short OS, and a combination of genes with LAMA2 could better predict short OS.

Low LAMA2 expression is significantly associated with chemoresistance and poor prognosis in OC. This association may involve crosstalk with LGR5 and Ras signaling pathways. Thus, LAMA2 may represent a candidate biomarker for predicting treatment response and survival outcomes, warranting further preclinical and clinical investigation.