Wang H, Wang W. Significance of serum APE1-AAbs, PTX-3, and miR-486-3p in patients with colorectal cancer undergoing radical surgery. World J Gastrointest Oncol 2025; 17(5): 105192 [DOI: 10.4251/wjgo.v17.i5.105192]
Corresponding Author of This Article
Wei Wang, Chief Physician, Department of Interventional Medicine, The Second Hospital of Shandong University, No. 247 Beiyuan Street, Jinan 250000, Shandong Province, China. xtx442@yeah.net
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Author contributions: Wang H designed the research study and performed the research; Wang W conducted the experiments and analyzed the data; Wang H and Wang W contributed to editorial changes in the manuscript, read and approved the final manuscript, and contributed equally as co-first authors.
Institutional review board statement: This study was approved by the Ethics Committee of Shandong Advanced Medical Research Institute.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wei Wang, Chief Physician, Department of Interventional Medicine, The Second Hospital of Shandong University, No. 247 Beiyuan Street, Jinan 250000, Shandong Province, China. xtx442@yeah.net
Received: January 15, 2025 Revised: February 17, 2025 Accepted: March 21, 2025 Published online: May 15, 2025 Processing time: 121 Days and 4.3 Hours
Abstract
BACKGROUND
Colorectal cancer (CRC) is a common malignant tumor of the digestive tract worldwide, characterized by high incidence and mortality rates.
AIM
To investigate the expression of serum apurinic/apyrimidinic endonuclease 1 autoantibodies (APE1-AAbs), peripheral pentraxin-3 (PTX-3), and miR-486-3p in patients with CRC undergoing radical surgery and their relationship with postoperative recurrence and metastasis.
METHODS
A retrospective analysis was conducted on the clinical data of 154 CRC patients who underwent laparoscopic radical surgery in our hospital from January 2022 to January 2024. Patients were followed for one year postoperatively and divided into an occurrence group (n = 28) and a non-occurrence group (n = 126) based on whether they experienced recurrence or metastasis. The clinical data and the expression levels of APE1-AAbs, PTX-3, and miR-486-3p were compared between the two groups. Multivariate logistic regression analysis was performed to identify risk factors for postoperative recurrence and metastasis in CRC patients. The relationship of APE1-AAbs, PTX-3, and miR-486-3p with postoperative recurrence and metastasis was analyzed using Spearman correlation analysis. Receiver operating characteristic curves were drawn to evaluate the predictive value of serum APE1-AAbs, PTX-3, and miR-486-3p levels alone and their combination for postoperative recurrence and metastasis in CRC.
RESULTS
The occurrence group had significantly higher proportions of patients with an age ≥ 60 years, lymph node metastasis, stage III disease, poor differentiation, tumor diameter > 5 cm, and higher platelet count, carcinoembryonic antigen, and carbohydrate antigen 19-9 levels than the non-occurrence group (P < 0.05). The expression levels of APE1-AAbs, PTX-3, and miR-486-3p in the occurrence group were significantly higher than those in the non-occurrence group (P < 0.05). Multivariate logistic regression analysis showed that lymph node metastasis, stage III disease, poor differentiation, and elevated levels of APE1-AAbs, PTX-3, and miR-486-3p were risk factors for postoperative recurrence and metastasis in CRC patients (odds ratio > 1, P < 0.05). Spearman correlation analysis revealed that the levels of APE1-AAbs, PTX-3, and miR-486-3p were positively correlated with postoperative recurrence and metastasis in CRC patients (r = 0.642, 0.653, and 0.631, respectively, P < 0.05). Receiver operating characteristic curve analysis showed that the area under the curve values for APE1-AAbs, PTX-3, and miR-486-3p levels alone and their combination in predicting postoperative recurrence and metastasis in CRC were 0.764, 0.783, 0.806, and 0.875, respectively, with the combination significantly outperforming individual markers (P < 0.05).
CONCLUSION
Serum APE1-AAbs, PTX-3, and miR-486-3p levels are higher in CRC patients with postoperative recurrence and metastasis. These three markers are risk factors for postoperative recurrence and metastasis in CRC and can be used as predictive biomarkers. The combined detection of these markers has higher predictive value compared to individual tests.
Core Tip: Serum apurinic/apyrimidinic endonuclease 1 autoantibodies, peripheral pentraxin-3, and miR-486-3p levels are higher in colorectal cancer patients with postoperative recurrence and metastasis. These three markers are risk factors for postoperative recurrence and metastasis in colorectal cancer and can be used as predictive biomarkers. The combined detection of these markers has higher predictive value compared to individual tests.
Citation: Wang H, Wang W. Significance of serum APE1-AAbs, PTX-3, and miR-486-3p in patients with colorectal cancer undergoing radical surgery. World J Gastrointest Oncol 2025; 17(5): 105192
Colorectal cancer (CRC) is a common malignant tumor of the digestive tract worldwide, characterized by high incidence and mortality rates[1]. Laparoscopic radical surgery for CRC effectively removes lesions, delays tumor progression, or improves cure rates. However, some patients may experience recurrence or metastasis due to incomplete tumor cell clearance, significantly affecting prognosis and survival[2,3]. Currently, monitoring postoperative recurrence and metastasis in CRC primarily relies on periodic tumor marker testing, imaging examinations, and clinical symptom evaluation. However, existing markers and methods have limitations, particularly in early recurrence and micrometastases, highlighting the need for highly sensitive and specific warning indicators[4,5]. Identifying new, reliable biomarkers for early diagnosis and prognostic evaluation has become a research hotspot in CRC studies.
Apurinic/apyrimidinic endonuclease 1 (APE1), a key DNA repair enzyme, plays a critical role in tumor genesis, progression, and drug resistance[6]. APE1 overexpression has been linked to various cancers, including breast cancer, lung cancer, and CRC, and it is involved in maintaining the genomic stability of tumor cells. Recent studies have suggested that APE1 autoantibodies (APE1-AAbs) could be used as potential biomarkers for CRC, as they may reflect early tumorigenic events and could help predict postoperative recurrence and metastasis[7]. Additionally, APE1-AAbs have been implicated in immune response modulation, which may contribute to cancer progression. Peripheral blood pentraxin-3 (PTX-3), an acute-phase protein, is significant in inflammatory diseases and tumorigenesis, particularly in immune evasion, metastasis, and prognosis evaluation in cancer[8]. PTX-3 levels are elevated in various cancers, including CRC, and have been shown to correlate with tumor progression, angiogenesis, and poor prognosis. PTX-3 plays a key role in the regulation of the innate immune response, and its elevated levels are believed to reflect systemic inflammation and tissue damage in cancerous environments, making it a promising candidate for post-surgical recurrence monitoring in CRC. MiR-486-3p, a microRNA closely related to tumor growth, metastasis, and invasion, has been found to be strongly associated with CRC development[9]. MiR-486-3p regulates key signaling pathways that control tumor cell proliferation and apoptosis, and its downregulation has been reported in several cancers, including CRC, where it correlates with increased tumor aggressiveness and poor patient outcomes. Studies have shown that miR-486-3p can also influence metastasis by modulating genes involved in cell migration and invasion. Given its role in CRC progression, miR-486-3p has emerged as a potential biomarker for monitoring disease recurrence and metastasis. Given the biological relevance of these biomarkers in CRC and their demonstrated prognostic value in other cancers, this study aimed to retrospectively analyze the predictive value of serum APE1-AAbs, PTX-3, and miR-486-3p levels for postoperative recurrence and metastasis in CRC patients.
MATERIALS AND METHODS
Study subjects
A retrospective analysis was conducted on the clinical data of 154 CRC patients who underwent laparoscopic radical surgery in our hospital from January 2022 to January 2024. The inclusion criteria were: (1) Meeting the diagnostic criteria for CRC as outlined in clinical guidelines[10]; (2) Undergoing elective laparoscopic radical surgery in our hospital with surgical indications; (3) Age ≥ 18 years, with no restriction on gender; (4) Expected survival time ≥ 3 months; (5) No prior biological therapy, radiotherapy, or chemotherapy before surgery; and (6) Complete and authentic clinical data available for analysis. The exclusion criteria included: (1) Presence of metastasis detected through preoperative imaging or intraoperative exploration; (2) Severe organ dysfunction or infection; (3) Coexisting gastrointestinal diseases; (4) Coexisting other malignant tumors and/or diseases of the immune or hematological systems; and (5) Cognitive, communication, or functional impairments and/or mental illnesses. This study was approved by the Ethics Committee of Shandong Advanced Medical Research Institute and complied with the principles of the Declaration of Helsinki[11] and relevant ethical requirements.
Treatment protocol
All the CRC patients included were treated by elective laparoscopic radical surgery in our hospital. Postoperative management followed standardized procedures, and all patients underwent comprehensive assessments within one month after surgery to determine chemotherapy contraindications. For patients without chemotherapy contraindications, adjuvant chemotherapy with the FOLFOX4 regimen was administered to reduce the risk of postoperative recurrence and metastasis. The specific treatment protocol was as follows: Oxaliplatin (Shandong New Era Pharmaceutical Co., Ltd., drug approval number: H20133247), administered at 85 mg/m² via intravenous infusion on the first postoperative day; calcium folinate (Jiangsu Hengrui Medicine Co., Ltd., drug approval number: H20000584), administered at 200 mg/m² via intravenous infusion on the first postoperative day; fluorouracil (Shanghai Xudong Haipu Pharmaceutical Co., Ltd., drug approval number: H31020593), administered at 400 mg/m² via intravenous bolus injection followed by 600 mg/m² via continuous intravenous infusion for 22 hours on the first and second postoperative days. During chemotherapy, specific interventions were employed to manage adverse reactions. A chemotherapy cycle was completed every two weeks, with a full treatment course spanning 28 days, totaling six cycles. For patients experiencing recurrence, metastasis, or intolerance to chemotherapy-related adverse reactions during treatment, individualized interventions were implemented, including chemotherapy discontinuation, regimen adjustment, or dose modification.
Detection of serum APE1-AAbs, PTX-3, and miR-486-3p levels
The serum levels of APE1-AAbs, PTX-3, and miR-486-3p in patients were measured using the following steps.
Serum sample collection and processing: Venous blood samples (7 mL) were collected from fasting patients using standard vacuum blood collection tubes to ensure sample integrity. The collected blood samples were centrifuged at 5300 rpm for 6 minutes with a radius of 5 cm to achieve proper separation. After centrifugation, the supernatant was carefully isolated to collect the serum while avoiding contamination by cellular components. The separated serum samples were stored at -35 °C to maintain the stability of bioactive molecules until further analysis.
Detection of APE1-AAbs and PTX-3 levels: Enzyme-linked immunosorbent assay was used for quantitative detection with a Smart Microplate Reader (Wuhan Yunclone Diagnostic Reagent Institute). Operational steps were as followed: Diluted serum samples were added to three parallel detection wells per EP tube, along with sample diluent, and mixed thoroughly. The microplate wells were sealed with a film and incubated at 37 °C for 47 minutes. After incubation, the liquid in the wells was discarded, and the wells were washed three times with a washing solution. A detection solution (102 μL) was added to each detection well, based on APE1-AAbs and PTX-3 detection kits (Quanzhou Ruixin Biotechnology Co., Ltd., and R&D Systems, United States, respectively). The contents were mixed thoroughly and allowed to react. Diluted carbonate buffer solution was added, and the plates were incubated overnight. The next day, the excess liquid was discarded, the wells were washed, and tetramethylbenzidine substrate solution was added to generate chromogenic products through enzymatic reactions. Optical density values were measured at a wavelength of 370 nm, and the levels of APE1-AAbs and PTX-3 in the samples were calculated.
Detection of miR-486-3p levels: The total RNA from serum was extracted using the QIAGEN RNeasy Mini Kit, strictly following the kit’s instructions to ensure RNA purity and integrity. The extracted RNA was reverse-transcribed into cDNA using the Aymetrix Reverse Transcription Kit. The reverse transcription reaction conditions were set according to the kit’s instructions to ensure efficient cDNA conversion. Quantitative real-time polymerase chain reaction (PCR) was performed using the ABI Step One fluorescence quantitative PCR instrument, with miRNA qPCR Mix as the reaction system and U6 as the internal control gene for relative quantification. The reaction system included 1 μL of forward primer, 1 μL of reverse primer, 6 μL of H2O, 2 μL of cDNA template, and 10 μL of miRNA qPCR Mix, making a total volume of 20 μL. The primer sequences are shown in Table 1. PCR conditions were as follows: Pre-denaturation at 94 °C for 3 minutes; 38 cycles of denaturation at 94 °C for 15 seconds, annealing at 60 °C for 30 seconds, and extension at 72 °C for 1 minute; and final extension at 72 °C for 10 minutes. The reaction curve was recorded using the real-time fluorescence quantitative PCR instrument. The relative expression level of miR-486-3p was calculated using the 2-ΔΔCt method.
Follow-up began on postoperative day 1 and continued for 1 year, with outpatient follow-ups conducted every 3 months. During follow-ups, patients underwent chest computed tomography (CT), abdominal ultrasound, and other examinations. Positron emission tomography-CT or chest and abdominal CT findings indicating anastomotic site metastasis, recurrence of the primary lesion, local lymph node metastasis, or distant organ metastasis were recorded as postoperative recurrence or metastasis. Scores were assigned based on the occurrence of recurrence or metastasis as follows: 1 point for independent recurrence or metastasis, 2 points for coexisting recurrence and metastasis, and 3 points for coexisting recurrence and metastasis with metastases involving more than one site. Recurrence and metastasis events for all patients were documented, and patients were divided into two groups based on whether postoperative recurrence or metastasis occurred (occurrence group and non-occurrence group).
Data collection
Factors potentially influencing postoperative recurrence and metastasis after laparoscopic CRC radical surgery were collected. These included age (< 60 years or ≥ 60 years), gender (male or female), comorbidities (hypertension, hyperlipidemia, or diabetes), body mass index, tumor growth pattern (infiltrative, expansive, or others), lymph node metastasis (yes or no), tumor-node-metastasis pathological stage (stages I–II, or stage III), tumor differentiation type (low differentiation, or moderate-high differentiation), vascular invasion (yes or no), nerve invasion (yes or no), tumor location (colon or rectum), tumor diameter (< 5 cm or ≥ 5 cm), chemotherapy (yes or no), and laboratory indicators [platelet count, white blood cell count, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9)].
Statistical analysis
GraphPad Prism 8 was used for graph plotting, and SPSS 22.0 was employed for data analyses. Measurement data were analyzed using the t-test, while count data, described as n (%), were analyzed using the χ2-test. Multivariate logistic regression analysis was conducted to identify factors influencing postoperative recurrence and metastasis in CRC patients. Spearman correlation analysis was performed to examine the relationships of APE1-AAbs, PTX-3, and miR-486-3p with postoperative recurrence and metastasis in CRC. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of APE1-AAbs, PTX-3, and miR-486-3p levels for postoperative recurrence and metastasis in CRC patients. The optimal cut-off values for each biomarker were determined using the Youden index method, which identifies the point on the ROC curve where the sum of sensitivity and specificity is maximized. This methodology has been widely used in previous studies for determining diagnostic thresholds. A P value < 0.05 was considered statistically significant.
RESULTS
Comparison of clinical data
The occurrence group showed higher proportions of patients with an age ≥ 60 years, lymph node metastasis, stage III disease, poor differentiation, and tumor diameter > 5 cm, as well as higher levels of PT, CEA, and CA19-9 compared to the non-occurrence group (P < 0.05) (Table 2).
Comparison of APE1-AAbs, PTX-3, and miR-486-3p levels
The levels of APE1-AAbs, PTX-3, and miR-486-3p in the occurrence group were 7.82 ± 3.47, 8.79 ± 1.95, 8.44 ± 1.63, respectively; whereas, in the non-occurrence group, the levels of APE1-AAbs, PTX-3, and miR-486-3p were 4.66 ± 2.15, 4.82 ± 1.35, 4.95 ± 0.89, respectively. The levels of APE1-AAbs, PTX-3, and miR-486-3p in the occurrence group were significantly higher than those in the non-occurrence group (P < 0.05) (Figure 1).
Figure 1 Comparison of apurinic/apyrimidinic endonuclease 1 autoantibodies, peripheral pentraxin-3, and miR-486-3p Levels.aP < 0.05 vs occurrence group. APE1-AAbs: Apurinic/apyrimidinic endonuclease 1 autoantibodies; PTX-3: Peripheral pentraxin-3.
Multivariate logistic regression analysis of factors affecting postoperative recurrence and metastasis in CRC
Postoperative recurrence and metastasis after CRC surgery were taken as the dependent variable (0 = no, 1 = yes). Potential influencing factors from Table 1 and Figure 1 were assigned values (Table 3) and included as independent variables in the multivariate logistic regression analysis model. The results showed that lymph node metastasis, stage III disease, low differentiation, APE1-AAbs, PTX-3, and miR-486-3p levels were risk factors for postoperative recurrence and metastasis in CRC (odds ratio > 1, P < 0.05) (Table 4).
Table 3 Variable assignment table of multivariate regression analysis.
Table 4 Multivariate logistic regression analysis of factors affecting postoperative recurrence and metastasis in colorectal cancer.
Factor
β
SE
Wald χ2
P value
OR
95%CI
Lymph node metastasis
1.078
0.364
8.682
< 0.001
2.946
1.294-6.706
Stage III disease
1.269
0.312
16.435
< 0.001
3.539
1.552-8.057
Low differentiation
1.145
0.414
7.654
< 0.001
3.146
1.377-7.151
APE1-AAbs
1.478
0.436
10.178
< 0.001
4.221
1.932-9.756
PTX-3
1.569
0.525
9.083
< 0.001
4.774
2.094-10.863
MiR-486-3p
1.416
0.367
15.456
< 0.001
4.103
1.799-9.328
Relationship of APE1-AAbs, PTX-3, and miR-486-3p levels with postoperative recurrence and metastasis of CRC
Spearman correlation analysis revealed that APE1-AAbs, PTX-3, and miR-486-3p levels were positively correlated with postoperative recurrence and metastasis of CRC (r = 0.642, 0.653, and 0.631, respectively, P < 0.05) (Figure 2, Table 5).
Figure 2 Relationship of apurinic/apyrimidinic endonuclease 1 autoantibodies, peripheral pentraxin-3, and miR-486-3p levels with postoperative recurrence and metastasis of colorectal cancer.
APE1-AAbs: Apurinic/apyrimidinic endonuclease 1 autoantibodies; PTX-3: Peripheral pentraxin-3; CRC: Colorectal cancer.
Table 5 Correlation analysis between APE1-AAbs, PTX-3, and miR-486-3p levels and postoperative recurrence and metastasis of colorectal cancer.
Parameter
r
P value
APE1-AAbs
0.642
< 0.001
PTX-3
0.653
< 0.001
MiR-486-3p
0.631
< 0.001
Predictive value of serum APE1-AAbs, PTX-3, and miR-486-3p levels alone and their combination for postoperative recurrence and metastasis of CRC
ROC curve analysis demonstrated that APE1-AAbs, PTX-3, and miR-486-3p individually had moderate predictive power for postoperative recurrence and metastasis in CRC, with area under the curve (AUC) values of 0.764, 0.783, and 0.806, respectively. However, when these biomarkers were combined, the AUC significantly increased to 0.875, indicating a much higher predictive accuracy (P < 0.05) (Figure 3, Table 6).
Figure 3 Receiver operating characteristic curves of apurinic/apyrimidinic endonuclease 1 autoantibodies, peripheral pentraxin-3, and miR-486-3p levels alone and their combination for predicting postoperative recurrence and metastasis of colorectal cancer.
APE1-AAbs: Apurinic/apyrimidinic endonuclease 1 autoantibodies; PTX-3: Peripheral pentraxin-3.
Table 6 Predictive value of apurinic/apyrimidinic endonuclease 1 autoantibodies, peripheral pentraxin-3, and miR-486-3p levels alone and their combination for postoperative recurrence and metastasis of colorectal cancer.
Indicator
Optimal cut-off value
AUC
95%CI
P value
Sensitivity, %
Specificity, %
APE1-AAbs
7.84 ng/mL
0.764
0.653-0.849
< 0.05
79.65
71.39
PTX-3
8.83 ng/mL
0.783
0.685-0.872
< 0.05
78.72
70.27
MiR-486-3p
8.49
0.806
0.709-0.891
< 0.05
85.69
72.51
Combination
0.875
0.782-0.943
< 0.05
92.84
90.35
DISCUSSION
In this study, among the 154 CRC patients who underwent laparoscopic radical surgery and were followed for one year, 28 experienced postoperative recurrence and metastasis, accounting for 18.18%. This proportion is slightly lower than the incidence (~30%) reported in previous studies[12]. The possible reasons for this discrepancy include the smaller sample size in this study and differences in the populations, lifestyle factors, and other aspects between the two studies. Multivariate logistic regression analysis showed that lymph node metastasis, stage III disease, and poor differentiation were risk factors for postoperative recurrence and metastasis in CRC (odds ratio > 1, P < 0.05). Previous studies[13,14] have also indicated that patients with lymph node metastasis, higher tumor-node-metastasis pathological stages, and lower tumor differentiation levels are at higher risk of CRC recurrence and metastasis after surgery. The findings of this study are consistent with these results, suggesting that clinical attention should be increased for patients with these risk factors.
APE1 is a key intracellular DNA repair enzyme involved in the removal of damaged bases from DNA and maintaining genome stability[15]. During the occurrence and progression of CRC, abnormal expression of APE1 is considered closely related to tumorigenesis, metastasis, and drug resistance[16]. APE1-AAbs are immune response products produced by the body against the APE1 enzyme. Elevated levels of APE1-AAbs may reflect the immune escape mechanisms of the body during tumorigenesis[17]. This study found that APE1-AAbs levels in the postoperative recurrence and metastasis group were significantly higher than those in the non-recurrence group and were positively correlated with recurrence and metastasis. Multivariate logistic regression analysis also demonstrated that APE1-AAbs are an independent risk factor for postoperative recurrence and metastasis in CRC. This suggests that APE1-AAbs may promote the survival, proliferation, and metastasis of tumor cells by binding to APE1 enzyme and affecting DNA repair mechanisms. As a DNA repair enzyme, APE1 is involved in repairing DNA damage within tumor cells, thereby helping tumor cells overcome DNA damage caused by chemotherapy or radiotherapy. This mechanism may enable tumor cells to evade immune surveillance and accelerate metastasis[18,19]. Therefore, APE1-AAbs may not only serve as a predictive marker for postoperative recurrence and metastasis in CRC but also provide insight into the molecular mechanisms of tumor immune escape.
PTX-3 is an acute-phase protein that is widely involved in inflammatory responses and immune regulation[20]. Abnormal elevation of PTX-3 plays an important role in the occurrence and progression of many tumors, particularly in the processes of tumor immune escape and metastasis. PTX-3 may promote tumor metastasis by regulating immune cells and inflammatory mediators in the tumor microenvironment[21,22]. This study showed that PTX-3 levels were significantly higher in the recurrence and metastasis group compared to the non-recurrence group, and PTX-3 levels were positively correlated with recurrence and metastasis. Multivariate logistic regression analysis also demonstrated that PTX-3 is an independent risk factor for postoperative recurrence and metastasis in CRC. The elevation of PTX-3 may reflect a persistent inflammatory response in CRC postoperative patients. This chronic inflammatory response not only promotes tumor cell growth and invasiveness but may also accelerate tumor metastasis through immune escape mechanisms[23]. Furthermore, PTX-3 interacts with tumor-associated macrophages and other immune cells to enhance immune tolerance within the tumor microenvironment[24], further facilitating CRC cell metastasis. Therefore, PTX-3 may not only serve as a biomarker for postoperative recurrence and metastasis but also provide a theoretical basis for new immunotherapy strategies.
MiR-486-3p is a microRNA closely related to tumor proliferation, metastasis, and invasion[25]. Numerous studies have demonstrated that miR-486-3p plays an important role in the occurrence and progression of various tumors, particularly in biological processes such as tumor cell proliferation, migration, and invasion[26,27]. MiR-486-3p can regulate the biological behavior of tumors by targeting multiple oncogenes or tumor suppressor genes[28]. This study found that miR-486-3p levels were significantly elevated in the recurrence and metastasis group and were positively correlated with postoperative recurrence and metastasis in CRC. Multivariate logistic regression analysis also revealed that miR-486-3p is an independent risk factor for postoperative recurrence and metastasis in CRC. The high expression of miR-486-3p may promote tumor cell proliferation and metastasis, leading to postoperative recurrence and metastasis in CRC. Studies have shown that miR-486-3p can target and regulate multiple signaling pathways related to tumor metastasis, such as the Wnt/β-catenin pathway and the PI3K/AKT pathway, thereby driving tumor cell invasion and migration[29,30]. Additionally, the high expression of miR-486-3p may be closely related to changes in the tumor microenvironment of CRC patients, influencing tumor angiogenesis and the response of tumor cells to the immune system.
In this study, the ROC curve analysis demonstrated that APE1-AAbs, PTX-3, and miR-486-3p individually had moderate predictive power for postoperative recurrence and metastasis in CRC, with AUC values of 0.764, 0.783, and 0.806, respectively. However, when these biomarkers were combined, the AUC significantly increased to 0.875, indicating a much higher predictive accuracy (P < 0.05). This result highlights the superiority of the combined biomarkers over individual markers, underscoring the added value of using a panel of biomarkers for predicting postoperative recurrence and metastasis in CRC patients. Moreover, when compared to conventional clinical markers, such as CEA and CA19-9, the combination of APE1-AAbs, PTX-3, and miR-486-3p demonstrated a markedly higher AUC. While traditional markers like CEA and CA19-9 are widely used in clinical practice, they typically exhibit AUC values ranging from 0.60 to 0.70, which are lower than the combined biomarker panel (AUC = 0.875). This suggests that the new biomarker panel may offer improved sensitivity and specificity, thereby providing more accurate prognostic information for detecting postoperative recurrence and metastasis in CRC patients. The combination of APE1-AAbs, PTX-3, and miR-486-3p holds great promise for clinical practice due to its superior sensitivity (92.84%) and specificity (90.35%) in predicting postoperative recurrence and metastasis. This could lead to earlier detection of recurrence and metastasis, which is critical for timely therapeutic interventions. Incorporating these biomarkers into clinical practice could provide a more reliable method for identifying high-risk patients, potentially leading to more personalized treatment strategies and improved patient outcomes. Given their high predictive value, APE1-AAbs, PTX-3, and miR-486-3p could complement existing diagnostic methods, such as CEA and CA19-9 testing, and serve as additional biomarkers for more comprehensive postoperative monitoring. These biomarkers may be particularly useful for detecting early-stage recurrence or metastasis, potentially reducing the reliance on imaging techniques that can be more costly and less sensitive in detecting early changes. By incorporating these biomarkers into routine clinical practice, clinicians may improve diagnostic accuracy and follow-up strategies for CRC patients.
Limitations
This study has several limitations that must be acknowledged. First, the retrospective design of this study means that potential biases, such as selection bias or incomplete clinical data, cannot be entirely ruled out. The observational nature of the study limits our ability to establish a causal relationship between biomarker levels and CRC recurrence or metastasis. Second, the sample size, although sufficient for this initial investigation, may not fully reflect the diversity of the broader CRC patient population. Larger, multicenter prospective studies are needed to confirm these findings and assess the generalizability of the results across different populations. Additionally, the lack of longitudinal data on treatment response and survival outcomes limits our ability to evaluate the long-term prognostic value of these biomarkers.
CONCLUSION
The findings of this study provide new insights into the early prediction of postoperative recurrence and metastasis in CRC. APE1-AAbs, PTX-3, and miR-486-3p show promising potential as biomarkers for early detection, with superior predictive accuracy compared to conventional markers. Beyond detecting recurrence, these biomarkers could influence treatment strategies by identifying high-risk patients who may benefit from more aggressive or personalized therapies. Their combined use may help guide decisions on postoperative surveillance intensity and therapeutic interventions, ultimately improving patient outcomes. Future studies should further validate these biomarkers and explore their integration with other molecular markers to enhance clinical management of CRC.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Oncology
Country of origin: China
Peer-review report’s classification
Scientific Quality: Grade B, Grade C, Grade C
Novelty: Grade C, Grade C, Grade C
Creativity or Innovation: Grade B, Grade B, Grade C
Scientific Significance: Grade B, Grade C, Grade C
P-Reviewer: Miled N; Moulay M; Zhang YC S-Editor: Wei YF L-Editor: Wang TQ P-Editor: Zhao S
Ryu HS, Kim J, Park YR, Cho EH, Choo JM, Kim JS, Baek SJ, Kwak JM. Recurrence Patterns and Risk Factors after Curative Resection for Colorectal Cancer: Insights for Postoperative Surveillance Strategies.Cancers (Basel). 2023;15:5791.
[RCA] [PubMed] [DOI] [Full Text][Reference Citation Analysis (0)]
Li Y, Jin-Si-Han EE, Feng C, Zhang W, Wang H, Lian S, Peng J, Pan Z, Li B, Fang Y, Lu Z. An evaluation model of hepatic steatosis based on CT value and serum uric acid/HDL cholesterol ratio can predict intrahepatic recurrence of colorectal cancer liver metastasis.Int J Clin Oncol. 2024;29:1263-1273.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 1][Reference Citation Analysis (0)]
Mejías-Trueba M, Saborido-Alconchel A, Serna-Gallego A, Trujillo-Rodríguez M, Muñoz-Muela E, Llaves-Flores S, Espinosa N, Roca-Oporto C, Herrero M, Sotomayor C, López-Cortes LF. Plasma concentrations of IL-6, MIP-1β, IP-10, and PTX-3 as predictors of the immunological response to antiretroviral treatment in people with HIV.Front Immunol. 2024;15:1447926.
[RCA] [PubMed] [DOI] [Full Text][Reference Citation Analysis (0)]
Hong JY, Oh HH, Park SY, Park YL, Cho SB, Joo YE. Expression of Apurinic/Apyrimidinic Endonuclease 1 in Colorectal Cancer and its Relation to Tumor Progression and Prognosis.In Vivo. 2023;37:2070-2077.
[RCA] [PubMed] [DOI] [Full Text][Reference Citation Analysis (0)]
Tomioka Y, Suetsugu T, Seki N, Tanigawa K, Hagihara Y, Shinmura M, Asai S, Kikkawa N, Inoue H, Mizuno K. The Molecular Pathogenesis of Tumor-Suppressive miR-486-5p and miR-486-3p Target Genes: GINS4 Facilitates Aggressiveness in Lung Adenocarcinoma.Cells. 2023;12:1885.
[RCA] [PubMed] [DOI] [Full Text][Reference Citation Analysis (0)]
