PINK1 Immunoexpression Predicts Survival in Patients Undergoing Hepatic Resection for Colorectal Liver Metastases

• Published in: International journal of molecular sciences 2023-03, Vol.24 (7), p.6506
• Main Authors: Celis-Pinto, Juan Carlos, Fernández-Velasco, Adela Alonso, Corte-Torres, María Daniela, Santos-Juanes, Jorge, Blanco-Agudín, Noelia, Piña Batista, Kelvin Manuel, Merayo-Lloves, Jesús, Quirós, Luis M, Fernández-Vega, Iván
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Cancer therapies; Colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - surgery; Comparative analysis; Development and progression; Hepatectomy; Humans; immunohistochemistry; Liver; Liver Neoplasms - secondary; Localization; Medical prognosis; Medical research; Medicine, Experimental; Metastases; Metastasis; Mutation; Patient outcomes; Patients; PINK1; Prognosis; Protein Kinases - genetics; PTEN protein; PTEN-induced putative kinase; Rectum; Retrospective Studies; Surgery; Survival; Survival analysis; Tumors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24076506

PTEN-induced kinase-1 (PINK1) is the initiator of the canonical mitophagy pathway. Our aim was to study the immunoexpression of PINK1 in surgical specimens from ninety patients with metastatic colorectal adenocarcinoma (CRC) to the liver (CRLM). Tissue arrays were produced, and immunohistochemical studies were analyzed by the H-Score method. The mean immunoexpression of PINK1 in normal tissues was between 40 to 100 points. In tumoral tissues, positive PINK1 immunoexpression was observed in all samples, and no differences were noted between CRCs. In CRLMs, a significant under-expression was noted for PINK1 from the rectum (71.3 ± 30.8; < 0.042) compared to other sites. Altered PINK1 immunoexpression in CRCs, either higher than 100 points or lower than 40 points, was associated with worse overall survival (OS) ( < 0.012) due to a shorter post-metastatic survival (PMS) ( < 0.023), and it was found to be a significant independent predictor of prognosis in a multivariate model for OS and PMS (HR = 1.972, 95% CI 0.971-4.005; = 0.022. HR = 2.023, 95% CI 1.003-4.091; = 0.037, respectively). In conclusion, altered PINK1 immunoexpression determined in CRCs with resected CRLM predicts a worse prognosis, possibly due to the abnormal function of mitophagy.