Long-Term Impact of HLA Class I Downregulation and Metastasis on Colon Cancer: An Analysis of Defective Models

Abstract

Background: Colorectal cancer (CRC) is a significant global health issue, particularly in Iran. Changes in human leukocyte antigen (HLA) class I expression are linked to tumor progression and patient survival. However, the long-term effects of changes in HLA class I expression on CRC outcomes, such as death, remain inadequately explored. Objectives: This study aims at utilizing a defective Marshall-Olkin Weibull model to evaluate cure fractions and the long-term effects associated with changes in HLA class I expression and metastatic status in patients with CRC. Methods: We conducted a retrospective cohort analysis involving 226 patients with CRC (aged 18 and older) diagnosed and treated at Shahid Beheshti University of Medical Sciences between 2005 and 2015. Participant eligibility was based on confirmed CRC diagnosis and treatment records. Data sources included medical records, with a mean follow-up period of 3.93 years. We assessed survival metrics from the time of diagnosis using the defective Marshall-Olkin Weibull model, controlling for age, gender, comorbidities, and potential biases in data selection. Results: Among the patients analyzed, 35.4% had no HLA class I expression, 53.1% exhibited downregulation, and 11.5% displayed high expression. The HLA downregulation (P = 0.0001) and metastasis (P = 0.001) were identified as strong negative predictors of cure rates. Compared to patients with downregulated HLA, those with high or no HLA expression had a cure rate 4.75 times higher, while non-metastatic patients showed a 3.63 times greater chance of cure. Conclusions: This study emphasizes the importance of cure models in identifying factors that impact survival and the adverse effects of low HLA class I expression on CRC prognosis. While the decade-long data collection period may limit generalizability due to evolving treatment standards and participant demographics, the findings suggest that strategies to restore HLA class I expression could improve CRC treatment outcomes.