Identification of a novel prognostic signature composed of 3 cuproptosis-related transcription factors in colon adenocarcinoma.

BACKGROUND

Since the mechanism of cuproptosis was recently revealed, many molecules related to this pathway have been widely concerned and exploited to have prognostic potential. However, it is still unknown whether the transcription factors related to cuproptosis could be competent as tumor biomarkers of colon adenocarcinoma (COAD).

OBJECTIVE

To analyze the prognostic potential of cuproptosis-related transcription factors in COAD, and validate the representative molecule.

METHODS

Transcriptome data and patients' clinical parameters were obtained from the TCGA and GEO database. 19 cuproptosis genes were identified through literature consulting. Cuproptosis-related transcription factors were screened by COX regression analyses. Multivariate Cox regression was applied to construct the signature. Prognostic effects were evaluated by Kaplan Meier survival analyses and ROC analyses. KEGG, GO, and ssGSEA analyses were performed for function prediction. 48 COAD tissues were collected for immunohistochemistry stain to observe the expression level and prognostic value of E2F3. qRT-PCR was performed to detect mRNA expression levels, while cell viability assay was applied to detect the response of COAD cells to elesclomol treatment.

RESULTS

A novel signature based on 3 prognostic transcription factors related to cuproptosis was successfully established and verified. Patients in the low-risk group tended to have better overall survival and lower immune phenotype scores than those in the high-risk group. Meanwhile, we also constructed a nomogram based on this signature and predict 10 candidate compounds targeting this signature. As an essential member of this signature, E2F3 was confirmed to be overexpressed in COAD tissues and was associated with poor prognosis of COAD patients. Importantly, CuCl2 and cuproptosis inducer elesclomol treatment could increase the expression of E2F3 in COAD cell while the overexpression of E2F3 significantly enhanced the resistance of COAD cells to elesclomol treatment.

CONCLUSION

Our research has identified a new prognostic biomarker and provides some innovative insights into the diagnosis and therapy of patients with COAD.