Relationship of TRAP1, HMGB1, and p62 expression with clinicopathologic features in colon cancer tissues

Abstract

BACKGROUND

Colorectal cancer yet remains one of the chief reasons that bring about cancer-connected sickness and decease in every region of the world. At present, we do not possess nearly sufficient reliable biological markers for the classification of patient risk and the completion of prognostic estimation work. An increasing number of investigations have begun to indicate that the advancement of tumors does not merely originate from alterations at the genetic level. This phenomenon is also pushed to move forward by the coordinated changes of cellular stress responses, mitochondrial function, and the tumor microenvironment. TRAP1 is one mitochondrion’s molecular chaperone which holds a function in the adjusting of metabolism and the adaptation to stress. HMGB1 plays the role of a key intermediary in the process of inflammation and the interactions between tumor and host. p62 is one scaffold protein which is related to autophagy. All three of the said molecules have connections to cancer biology in early studies. Having said this point, most research works have only examined these molecules each by themselves. How much each of them contributes when it is considered under a unified clinicopathological circumstance is still not well comprehended. The systematic observation of their expression modes and clinical meanings in colon cancer therefore could assist us in constructing a more comprehensive cognition of their functions. This thing also can possibly let us see how much use they can have as prediction biological marks.

AIM

To measure the expression levels of TRAP1, HMGB1, and p62 in colon cancer tissue samples. To compare the expression patterns of these three markers between tumor tissues and matched adjacent normal mucosal tissues. To analyze their associations with patients’ clinicopathologic characteristics and follow-up outcomes.

METHODS

We have carried out a retrospective enrollment of 120 patients in total. All of these people had first-stage colon cancer, underwent surgical cutting removal, and obtained pathological verification at one single hospital within the period from October 2022 to October 2025. We have utilized the method of immunohistochemistry to examine the expression situations of TRAP1, HMGB1, and p62. In these samples, there are included 120 tumor specimens and their matching neighboring normal mucosa tissues. Another point which has worth to mention is that we have selected 40 paired fresh specimens to carry out reverse transcription-polymerase chain reaction analysis. We have gotten together a number of clinical changeable factors. These items include age, sex, tumor position, tumor dimension, differentiation degree, invasion depth, lymph node metastasis, TNM stage, lymphatic vessel invasion, and perineural invasion. The follow-up work was continued until the month of March in the year 2026. We regard overall survival as the endpoint of our study. We have done all statistical analyses by using paired t test, χ² test or Fisher’s exact test, Kaplan-Meier analysis, and Cox regression model building.

RESULTS

The high expression rate of TRAP1, HMGB1, and p62 in colon cancer organization were 52.5%, 48.3%, and 45.0%, respectively, all of which were higher than those in matched near normal mucous membrane (20.0%, 15.8%, and 17.5%, respectively; all of P values are smaller than 0.001). Reverse transcription-polymerase chain reaction detection displayed that the relative mRNA expression amounts of TRAP1, HMGB1, and p62 are all higher in tumor tissues than in adjacent tissues (all P < 0.001). The expression level of TRAP1 that is high had connection with tumor diameter which is bigger than or equal to 5 cm, bad differentiation, stage of T3-4, metastasis of lymph node, stage of TNM III-IV, invasion of lymphovasculature, and invasion around nerve (all P < 0.05). The expression level of HMGB1 that is relatively high was connected with bad differentiation, lymph node metastasis, and TNM stage III-IV (all P < 0.05). The high expression level of p62 was also related to the bad differentiation degree, lymph gland metastasis shift, and TNM stage III-IV, all these have P < 0.05. Multivariable logistic regression analysis has indicated that lymphovascular invasion, high expression level of TRAP1, and high expression level of HMGB1 are independent correlation factors of lymph node metastasis. The follow-up time of the median is 26 months, in this period 24 death events happened. Kaplan-Meier analysis has demonstrated that patients who hold high TRAP1, HMGB1, or p62 expression possess lower overall survival than the corresponding groups with low expression (all P < 0.05). Exploratory multivariable Cox regression analysis put forward that lymph node metastasis, lymphovascular invasion, and high TRAP1 expression had connections with bad total survival.

CONCLUSION

In colon cancer tissues, TRAP1, HMGB1 and p62 are significantly overexpressed and closely correlated with adverse clinicopathological features. Of the three biomarkers, TRAP exhibits the most prominent correlation with lymph node metastasis and overall survival. Nevertheless, the relatively wide 95% confidence interval for its hazard ratio weakens the robustness of its prognostic efficacy; accordingly, the present results are insufficient to support its immediate clinical implementation for risk stratification. Despite such limitations, TRAP still has promising potential as a prognostic indicator, which requires further validation in larger cohorts with prolonged follow-up periods.

Keywords: Colon cancer; TRAP1; HMGB1; P62; Immunohistochemistry; Reverse transcription-polymerase chain reaction; Prognosis

Core Tip: This study investigated the expression of TRAP1, HMGB1, and p62 in colon cancer tissues, all of which were significantly upregulated compared with adjacent normal mucosa at both protein and mRNA levels. Their high expressions were closely associated with adverse clinicopathological features including poor differentiation, lymph node metastasis, and advanced TNM stage. TRAP1 was identified as an independent predictor for lymph node metastasis and poor overall survival, showing superior prognostic value. HMGB1 also independently predicted lymph node metastasis, while p62 was correlated with tumor progression but lacked independent prognostic significance. These findings suggest that TRAP1, HMGB1, and p62 serve as promising biomarkers for colon cancer, with TRAP1 being particularly valuable for prognostic assessment.