Background The preliminary study is conducted to investigate the role of ferroptosis-related protein GPX4 and HSPA5 in the progression of colorectal cancer, providing evidence for exploring the mechanisms of occurrence and development of colorectal cancer and finding new therapeutic targets.

Methods The study analyzed GPX4 and HSPA5 expression in colorectal cancer tissues and the correlation with survival time on an online database. Then, we collected cancer tissues and adjacent tissue samples, taken from patients initially diagnosed with colorectal cancer and undergoing radical surgery in Inner Mongolia People’s Hospital between May 2022 and April 2023. We assessed GPX4 and HSPA5 expression in colorectal cancer and adjacent tissues using immunohistochemistry, examined the relationship with clinical and pathological data, as well as the correlation between GPX4 and HSPA5 expression and serum carcinoembryonic antigen in colorectal cancer tissues.

Results The results indicated that GPX4 and HSPA5 exhibited differential expression in colorectal cancer tissues (P<0.001), with the overall survival rate of patients in the GPX4 low-expression group being higher than that of those in the high-expression group (P<0.05). Similar results were observed for HSPA5, yet the difference was not significant (P>0.05). The results also showed that GPX4 and HSPA5 were primarily localized in the cytoplasm, and the positive rate in colorectal cancer tissues was higher than that in adjacent tissues significantly. They were associated with tumor infiltration depth and lymph node metastasis, respectively (P<0.05). GPX4 expression was positively correlated with serum carcinoembryonic antigen levels in patients‘ preoperative serum (P<0.05). There was a significant positive correlation between GPX4 and HSPA5 expression in colorectal cancer (r=0.394, P<0.05).

Conclusions GPX4 and HSPA5 are highly expressed in colorectal cancer, which is associated with invasion depth and lymph node metastasis, respectively. The positive correlation between GPX4 and HSPA5 expression indicates that they mediate the ferroptosis process to regulate the occurrence and development of colorectal cancer, leading to poor prognosis for patients. Furthermore, GPX4 expression is significantly correlated with serum carcinoembryonic antigen levels, offering evidence for the combined detection of colorectal cancer.