Integrated Bioinformatics Analysis Reveals the Clinical and Epigenetic Significance of PYCR1 as a Diagnostic, Prognostic, and Therapeutic Biomarker in Lung Adenocarcinoma

Abstract

Lung adenocarcinoma (LUAD) is still one of the main causes of death from cancers globally; hence, there is a need for developing new biomarkers and targets for diagnosis and treatment. This work involves analyzing the involvement of Pyrroline-5-carboxylate reductase 1 (PYCR1) through multidimensional bioinformatic approaches on LUAD data obtained from „The Cancer Genome Atlas (TCGA)‟ portal-UALCAN. Our findings indicate that PYCR1 is highly expressed in LUAD tissue samples than normal lungs (p < 1E-12) with a consistent increase in its expression irrespective of age group, gender, or smokers/non-smokers. Elevated PYCR1 was positively associated with more advanced clinical stages of tumors and lymph node metastasis. Moreover, we found that the expression of PYCR1 is highly up-regulated in response to TP53 mutations with hypomethylation of its promoter, thus implying a novel mechanism of transcriptional activation of PYCR1. Notably, the analysis showed that high expression of PYCR1 is an independent marker predicting poor survival. This makes PYCR1 a reliable biomarker with both diagnostic and prognostic value and demonstrates the significance of a metabolic-genetic axis in cancer development. The study concludes that PYCR1 proline pathway modulation can be used as a novel therapy to treat lung adenocarcinoma.