Abstract
-
Purpose
- Colorectal cancer (CRC) is the most common malignancy of the gastrointestinal system globally. Identifying specific gene expression patterns indicative of early-stage CRC could enable early diagnosis and rapid treatment initiation. Matrix metalloproteinases (MMPs) play crucial roles in extracellular matrix degradation and tissue remodeling. Among them, MMP-2 and MMP-9 have been found to be upregulated in various cancers, including CRC, and are associated with tumor invasion, metastasis, and angiogenesis. In contrast, a disintegrin and metalloproteinase like decysin 1 (ADAMDEC1) is a relatively newly discovered gene with demonstrated involvement in immune response and inflammation. This study investigated serum levels of MMP-2 and MMP-9, along with tissue expression of MMP-2, MMP-9, and ADAMDEC1, and explored potential associations with pathological and clinical factors in patients with CRC.
-
Methods
- This study included 100 patients with CRC and 100 control participants. Tissue and blood samples were collected. Serum MMP-2 and MMP-9 levels were analyzed using the enzyme-linked immunosorbent assay. Quantitative real-time polymerase chain reaction was employed to assess the expression levels of MMP-2, MMP-9, and ADAMDEC1 in CRC tissue samples compared to adjacent control tissue.
-
Results
- The expression levels of MMP-2, MMP-9, and ADAMDEC1 were significantly upregulated in CRC relative to adjacent control tissues. Analysis of clinicopathological features revealed statistically significant differences in the expression levels of MMP-2, MMP-9, and ADAMDEC1 between patients with CRC with and without lymphovascular invasion (P<0.001). Based on receiver operating characteristic curve analysis, these genes represent promising candidate diagnostic biomarkers for CRC.
-
Conclusion
- MMP-2, MMP-9, and ADAMDEC1 levels may serve as potential diagnostic biomarkers for CRC.
-
Keywords: Colorectal neoplasms; ADAMDEC1; Matrix metalloproteinase 2; Matrix metalloproteinase 9
INTRODUCTION
Colorectal cancer (CRC), the third most common cancer in the world, is responsible for 8% of all cancer-related deaths globally [1]. CRC causes more than 800,000 deaths each year [2]. The prevalence of CRC in younger age groups is increasing around the world [3]. CRC typically does not show symptoms in its early stages; thus, this disease is often diagnosed after the tumor has invaded local lymph nodes and metastasis has occurred [2]. Therefore, CRC is considered a serious health risk, highlighting the need to identify key signaling pathways involved in its development. Identifying markers that enable early diagnosis and expedite treatment is essential.
Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes with zinc-dependent activity. MMPs play a key role in normal physiological tissue regeneration and the degradation of extracellular matrix components. Evidence indicates that metalloproteinases are involved in cancer progression. These enzymes can activate growth factors and promote protease secretion, ultimately facilitating tumor cell invasion of the extracellular matrix. MMPs involved in tumor angiogenesis also regulate the formation and maintenance of the tumor microenvironment. Two members of this family, MMP-2 and MMP-9, contribute to angiogenesis in CRC. These metalloproteinases degrade basement membrane components, such as type IV collagen, the degradation of which represents an important step in tumor invasion [1, 4].
The “a disintegrin and metalloproteinase” (ADAM) family binds to cell membranes and contains metalloproteinase and disintegrin functional domains. Members of the ADAM family participate in processes such as neurogenesis, immune response, extracellular matrix hydrolysis, cell-cell adhesion, and cell-matrix adhesion. In diseases related to the inflammatory response, cell-cell and cell-matrix interactions play crucial roles. Disruption in the regulation of ADAMs contributes to inflammatory diseases and cancers. ADAMs can interfere with cell adhesion and promote cell necrosis. ADAM-like decysin 1 (ADAMDEC1) is a member of the ADAM family. Like other ADAM family members, ADAMDEC1 contributes to the development of many diseases by regulating inflammation. Repression of ADAMDEC1 results in decreased levels of interleukin 6, inducible nitric oxide synthase, and tumor necrosis factor α, thereby reducing the inflammatory response. Studies suggest that ADAMDEC1 is involved in cancer development, and in some cancers, such as gastric cancer, ADAMDEC1 regulates cell proliferation and migration. The ADAM gene-related family, including ADAMDEC1, is involved in the pathogenesis of CRC and promotes invasion by stimulating epithelial-mesenchymal transition (EMT) [3, 5]. In CRC, ADAMDEC1 facilitates the metastasis of cancer cells. However, the expression pattern and function of metalloproteinases, as well as the exact role of ADAMDEC1 in cancer progression, remain largely unclear in this context. Due to the role of ADAMDEC1 in other cancers, we decided to investigate the ADAMDEC1 prognostic signature in CRC.
This study was conducted to investigate the roles of MMP-2, MMP-9, and ADAMDEC1 in CRC. Using real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), we examined the expression of the MMP-2, MMP-9, and ADAMDEC1 genes in tissue and serum samples from patients with colon cancer with and without lymphovascular invasion (LVI) and evaluated the relationship between their expression patterns and the severity of tumor progression. We also aimed to explore the relationship between the expressions of MMP-2/MMP-9 and the activation of the ADAMDEC1 pathway, which has not been previously investigated. Accordingly, the present research was performed to further investigate the cellular and molecular mechanisms of CRC. Evaluating these genes can increase our understanding of the cellular pathways involved in colon cancer, and the information obtained from this study may potentially aid in drug design.
METHODS
Ethics statement
The study was approved by the Ethics Committee of Iran University of Medical Sciences (No. IR.IUMS.REC.1402.1055). Written informed consent was obtained from all participants before enrollment. All procedures involving human participants in this study were conducted in accordance with the ethical standards of Iran University of Medical Sciences (Tehran, Iran).
Patients and samples
This case-control study collected tissue samples from patients referred to Rasuol Akram Hospital (Tehran, Iran) from July 2020 to December 2022. A total of 100 patients and 100 control participants were included, and samples were collected through biopsies or surgical resections. For control tissue samples, normal tissue specimens were obtained from patients with CRC; these specimens contained no tumor cells and were taken from tissue located less than 2 cm away from the tumor site. The inclusion criteria were age between 20 and 65 years, tumor tissue sample histologically confirmed as colon adenocarcinoma by a board-certified pathologist, and no receipt of any CRC-associated therapy prior to biopsy. Participants who received CRC-associated therapy or surgical resections, as well as patients with any other malignancies, were excluded from the study. Demographic, lifestyle, and histopathological information, including clinical TNM staging, was recorded for all selected individuals. Furthermore, a 6-mL peripheral blood sample was obtained from each participant via venipuncture under complete aseptic conditions and centrifuged at 1,000×g for 10 minutes to separate the serum for MMP-2 and MMP-9 assays. All samples were stored at −80 °C until analysis of serum MMP-2 and MMP-9 levels and RNA extraction.
Measurement of serum MMP-2 and MMP-9
Serum levels of MMP-2 and MMP-9 were assessed using ELISA kits following the manufacturer’s instructions. The sensitivity of the human MMP-2 and MMP-9 ELISA kits (ZellBio) was 5 pg/mL. Briefly, 40 µL of sample combined with 10 µL of MMP-2 or MMP-9 antibody, 50 µL of standards, and 50 µL of streptavidin-HRP were added to each well, and the plate was incubated at 37 °C for 60 minutes. After washing 5 times, 100 µL of chromogen was added, and the plate was again incubated at 37 °C for 10 minutes. Finally, 50 µL of stop solution was added, and the optical density was measured at 450 nm using an ELISA reader.
RNA extraction from tissue samples and complementary DNA synthesis
RNA was extracted using a kit (Cinnacolon) in accordance with the manufacturer’s instructions, and the isolated RNA was eluted in 40 µL of RNase-free water (Cinnacolon). The concentration and integrity of the total RNA were assessed by measuring the A260/A280 ratio using a NanoDrop ND-1000 spectrophotometer (Thermo Fisher Scientific). The desired ratio for each sample was between 1.7 and 2.1. The RNA suspension was then stored at −80 °C for further analysis and conversion to complementary DNA (cDNA). Reverse transcription was performed using a cDNA synthesis kit (Cinnacolon), and cDNA was prepared from 2 μg of total RNA using oligo(dT) and random hexamer primers. Consistent with the manufacturer’s direction, the reaction was run on a PCR thermocycler as follows: 10 minutes at 25 °C, 2 hours at 37 °C, and 5 minutes at 85 °C. The resulting cDNA was diluted to a total concentration of 5 ng/μL.
Real-time PCR
To analyze the expression levels of MMP-2, MMP-9, and ADAMDEC1 using real-time PCR, 2.0X Real Q-PCR Master Mix with SYBR Green (Ampliqon) was used. The reaction mixture consisted of 10 µL of 2X Real Q-PCR Master Mix, 1 µL of cDNA, 1 µL of each primer (10 pmol/µL), and 8 µL of distilled water, with a final volume of 20 µL. Reactions were run on the StepOnePlus Real-time PCR System (Applied Biosystems) using the following thermal cycling parameters: 95 °C for 2 minutes, followed by 40 cycles of 95 °C for 5 seconds and 60 °C for 30 seconds. Melting curve analysis confirmed the specificity of the products. Gene expression levels were normalized using β2 microglobulin as the housekeeping gene. The primers were designed to span exon-exon junctions of MMP-2, MMP-9, and ADAMDEC1 to avoid false-positive results due to DNA contamination (Supplementary Table 1).
Statistical analysis
Serum levels of MMP-2 and MMP-9 were analyzed using GraphPad Prism ver. 8.0 (GraphPad Software Inc), with the data presented as mean±standard deviation. Efficiency values, cycle threshold (Ct) for each sample, and amplification efficiency were determined using LinReg ver. 2017.1 (Academic Medical Center, University of Amsterdam). The gene expression ratios (fold change calculated as 2–ΔCt) for MMP-2, MMP-9, and ADAMDEC1 were estimated using REST 2009 (Qiagen). Statistical differences in MMP-2, MMP-9, and ADAMDEC1 gene expression levels between patients and controls were analyzed using GraphPad Prism with the Mann-Whitney test and the unpaired t-test. For correlation analyses, GraphPad Prism ver. 8 was used, and the Spearman rank correlation coefficient was employed to assess relationships between variables. This nonparametric test was chosen because it is less sensitive to outliers and does not assume a normal data distribution. A P-value of <0.05 was considered to indicate statistical significance.
RESULTS
Demographic characteristics
Overall, we analyzed 100 patients with CRC aged 43.91±9.73 years (range, 20–65 years), of which 52 were female and 48 were male. The malignancy was in the colon in 45 patients and in the rectum in 55 patients. Additionally, 35 patients had inflammatory bowel disease (IBD), 30 had polyps, and 35 had colitis. Regarding pathologic staging (TNM system), 29 patients were stage II, 36 were stage III, and 35 were stage IV. LVI positive (LVI+) status was observed in 40 of the 100 patients (40%). The clinicopathological characteristics of the selected participants are presented in Table 1.
Serum MMP-2 and MMP-9 levels
Serum MMP-2 levels were measured at 6.095±2.326 pg/mL in the patients with CRC, compared to 2.081±0.8470 pg/mL in the control group (Fig. 1). The Mann-Whitney test, used due to the non-normal distribution of the data, indicated a statistically significant difference in serum MMP-2 levels between the control and CRC groups (P<0.001). Similarly, the mean serum MMP-9 levels were 6.685±2.267 pg/mL in the patients with CRC and 2.320±0.9319 pg/mL in the control participants, with the Mann-Whitney test revealing a statistically significant difference (P<0.001). Among the patients with CRC, the analysis also revealed statistically significant differences in serum MMP-2 and MMP-9 levels between those with and without LVI, with P-values of <0.001 and <0.009, respectively (Fig. 1). No significant difference was found in serum MMP-2 levels across TNM stages (P<0.777), while serum MMP-9 levels did differ significantly across stages (P<0.007). Furthermore, no significant differences were observed in serum MMP-2 and MMP-9 levels among the patients with CRC with regard to their history of colitis, IBD, or polyps (P<0.818 and P<0.063, respectively).
Gene expression levels of MMP-2, MMP-9, and ADAMDEC1
Quantitative real-time PCR analysis demonstrated that the gene expression levels of MMP-2, MMP-9, and ADAMDEC1 were significantly upregulated in CRC tissue samples compared to normal tissue (all P<0.001) (Fig. 2). Based on receiver operating characteristic (ROC) curve analysis, tissue expression of these markers may serve as useful biomarkers to distinguish patients with colorectal adenocarcinoma from individuals without the disease. The areas under the ROC curve for MMP-2, MMP-9, and ADAMDEC1 are shown in Fig. 3, with a larger area indicating higher diagnostic value. No significant differences were found in the tissue expression levels of MMP-2, MMP-9, or ADAMDEC1 among the patients with CRC regarding their history of colitis, IBD, and polyps (P=0.569, P=0.190, and P=0.142, respectively). Additionally, tissue expression levels of MMP-2 did not differ significantly across TNM stages (P<0.175). However, significant differences were observed in tissue expression levels of MMP-9 and ADAMDEC1 across TNM stages; specifically, MMP-9 and ADAMDEC1 expression levels were significantly higher in patients with stage IV CRC compared to those in stages II and III, with P-values of 0.031 and 0.003, respectively. LVI was observed in 40 of the 100 patients (40%) with CRC. Analysis revealed statistically significant differences in the expression levels of MMP-2, MMP-9, and ADAMDEC1 between LVI+ and LVI negative (LVI–) patients (all P<0.001). Specifically, expression levels of all 3 biomarkers were significantly higher in the LVI+ group compared to the LVI– group (Fig. 4).
Correlations between serum concentrations and gene expression levels of MMP-2 and MMP-9
GraphPad Prism ver. 8 was used for correlation analyses. Tissue expression levels of MMP-2, MMP-9, and ADAMDEC1 were quantified using 2−ΔCt values, providing a normalized measure of gene expression. The Spearman rank correlation coefficient was employed to assess relationships between variables, as this nonparametric test is less sensitive to outliers and does not assume a normal data distribution. A P-value of <0.05 was considered to indicate statistical significance. The Spearman correlation analysis yielded the following results: no significant correlations were found between serum levels of MMP-2/MMP-9 and cancer stage; however, tissue expressions of these enzymes demonstrated clearer relationships. Specifically, tissue MMP-2 expression exhibited a weak positive correlation with cancer stage (r=0.2243; 95% confidence interval [CI], 0.02326 to 0.4079; P=0.024) and a strong negative correlation with LVI (r=−0.4833; 95% CI, −0.6244 to −0.3117; P<0.001). Similarly, tissue MMP-9 expression was weakly positively correlated with cancer stage (r=0.2109; 95% CI, 0.009249 to 0.3961; P=0.035) and strongly negatively correlated with LVI (r=−0.7085; 95% CI, −0.7965 to −0.5910; P<0.001). Additionally, tissue ADAMDEC1 expression displayed a weak positive correlation with cancer stage (r=0.3319; 95% CI, 0.1391 to 0.5004; P=0.007) and a strong negative correlation with LVI (r=−0.7795; 95% CI, −0.8480 to −0.6854; P<0.001). Positive correlations were also observed between tissue expressions of MMP-2 and MMP-9 (r=0.4028; 95% CI, 0.2186 to 0.5594; P<0.001) and between each of these and ADAMDEC1 (MMP-2: r=0.3771 [95% CI, 0.1895 to 0.5382], P=0.001; MMP-9: r=0.5729 [95% CI, 0.4194 to 0.6946], P<0.001), highlighting possible co-regulatory mechanisms within the tumor microenvironment. The absence of significant correlations of serum MMP-2 and MMP-9 levels with cancer stage or with each other suggests that the prognostic or therapeutic relevance of these markers may be primarily confined to tissue-specific expressions. Regarding correlations between serum and tissue levels, the results were mixed. Serum and tissue MMP-2 did not exhibit a significant correlation, suggesting distinct regulatory mechanisms or localized expression patterns that do not reflect systemic levels. In contrast, the correlation between serum and tissue MMP-9 was weakly positive but significant (r=0.2166; 95% CI, 0.01519 to 0.4011; P=0.030), indicating a slight parallel in their expression across compartments (Table 2).
DISCUSSION
Recent efforts in CRC research have meaningfully improved treatment outcomes for this cancer [6]. CRC is expected to become the second most common cancer by the year 2040 [7, 8], and identifying prognostic markers at both genomic and proteomic levels is essential for early diagnosis [1]. MMPs are involved in tumor metastasis; in particular, MMP-2 and MMP-9 play important roles in cancer invasion by degrading type IV collagen [9]. ADAMDEC1, a member of the ADAM family of metalloproteinases, is a secreted protease. Studies suggest that ADAMDEC1 could serve as a biomarker for early CRC detection and may be associated with poor prognosis [3]. We attempted to demonstrate the role of ADAMDEC1 in CRC proliferation and invasion. Our results suggested that serum levels of MMP-2 and MMP-9 differed significantly between patient and control samples. However, we found no significant differences in the serum levels of MMP-2 and MMP-9, or in the tissue expression levels of MMP-2, MMP-9, and ADAMDEC1, among patients with CRC with a history of IBD, colitis, and polyps. Overall, the expression levels of MMP-2, MMP-9, and ADAMDEC1 were elevated in CRC tissue samples compared to controls. The absence of a significant correlation between serum and tissue levels of MMP-2 and MMP-9 suggests that systemic and local expression of these genes may be regulated independently.
In contrast, we observed increased expression of MMP-2, MMP-9, and ADAMDEC1 in the LVI+ group. The strong positive correlations observed between these markers and LVI indicate that higher tissue expression is associated with LVI. LVI signifies the presence of cancer cells in lymphatic or vascular channels and is indicative of lymph node metastasis [10]. To explain the correlation of ADAMDEC1 expression with MMP-2 and MMP-9 levels, one must consider the signaling pathways in which these genes are involved. ADAMDEC1, along with MMP-9, contributes to metallopeptidase activity [11]. In CRC, LVI is recognized as a principal, stage-independent prognostic factor. In malignant CRC polyps, lymphatic invasion increases the likelihood of regional lymph node metastases [12]. Because MMPs contribute to extracellular matrix degradation and basement membrane destruction, they facilitate tumor invasion. Research suggests that overexpression of MMP-2 and MMP-9 in endometrial carcinoma is correlated with LVI. As such, the correlation between MMP-2 and MMP-9 overexpression and LVI can be explained, also supporting the observed upregulation of these genes in the tissue samples [12]. Nevertheless, further studies with larger samples are needed to better evaluate the effects of LVI and elucidate the relevance of MMP-2, MMP-9, and ADAMDEC1 expression levels in this invasion.
We also demonstrated that tissue levels of ADAMDEC1, MMP-2, and MMP-9 exhibit weak positive correlations with cancer stage, indicating their potential involvement in cancer progression. Some prior research has indicated that MMP-9 is a marker of aggressive CRC and is associated with increased lymph node involvement [13]. Lu et al. [14] showed that MMP-2 overexpression may contribute to lymphatic invasion in CRC. Other research on CRC has also revealed increased expression of MMP-2 and MMP-9 in tumor tissue compared to normal tissue, corroborating our findings [15]. Experimental studies have demonstrated overexpression of MMP-2 and MMP-9 in IBD. For instance, in patients with ulcerative colitis [16], overexpression of MMP-2 and MMP-9 leads to tissue degradation, tissue remodeling, and increased inflammation [17]. This MMP overexpression is associated with the ulcerative colitis phenotype. Additionally, Jakubowska et al. [17] reported ADAMDEC1 expression in ulcerative colitis samples and proposed ADAMDEC1 as a novel marker for IBD. Research has also shown that the expression levels of MMP-9 and MMP-2 are increased in adenomatous polyps [4, 18]. In this study, we sought to determine the correlation of MMP-2 and MMP-9 expression with ADAMDEC1 levels. Research on glioblastoma multiforme (GBM) indicates that ADAMDEC1, through activation of the MMP-2 pathway, promotes GBM progression. That study showed that ADAMDEC1 is positively correlated with the presence of CD8+ T cells and negatively correlated with that of CD4+ T cells. Indeed, ADAMDEC1 influences immune cells and contributes to GBM progression [5]. Another study has shown that T cells are involved in the secretion of MMP-2 and MMP-9 [19], suggesting that ADAMDEC1 may affect the secretion of these MMPs by modulating T-cell activity.
Previous research on the role of ADAMDEC1 in CRC indicates that it activates the Wnt/β-catenin signaling pathway by inhibiting glycogen synthase kinase-3β (GSK-3β), thus enhancing EMT and metastasis. GSK-3β acts as an inhibitor of the Wnt/β-catenin pathway; its inactivation leads to the accumulation of β-catenin in the cytoplasm, resulting in pathway activation. Nuclear β-catenin binds to the transcription factors T-cell factor/lymphoid enhancer factor, thereby inducing EMT. Jia et al. [3] showed that reducing ADAMDEC1 levels decreases the activity and production of MMP-2 and MMP-9, whereas increasing ADAMDEC1 promotes their activity and expression. In contrast, activation of the Wnt/β-catenin pathway in CRC upregulates MMP-9 and MMP-2 expression [20]. MMPs tend to function in signaling cascades in which they activate other MMPs. For example, MMP-2 and MMP-13 promote cleavage of the prodomain of pro-MMP-9, facilitating its activation [19]. Another pathway that may explain the connection between ADAMDEC1 and MMP-2/MMP-9 is the ADAMDEC1-fibroblast growth factor 2 (FGF2)-FGF receptor 1 (FGFR1) axis. One study demonstrated that ADAMDEC1 induces FGF2 signaling via FGFR1 and supports glioblastoma cancer stem cell maintenance by promoting the stem cell transcription factor zinc finger E-box binding homeobox 1 (ZEB1). Furthermore, ZEB1 increases ADAMDEC1 expression, establishing a positive feedback loop [21]. Conversely, zymographic analyses have shown that FGF2 induces MMP-2 and MMP-9 activity [22]. Another study suggests that in non-small cell lung cancer, ADAMDEC1 activates the PI3K/AKT pathway, promoting cancer progression [3]. Xu et al. [23] showed that activation of the PI3K/Akt/mTOR signaling pathway increases MMP-2 and MMP-9 expression in cancer cells and exacerbates metastasis.
These findings contribute to a deeper understanding of the molecular relationships in CRC and highlight potential biomarkers for disease progression and invasion. Further research is warranted to validate these associations and explore their functional implications.
In conclusion, these results suggest that MMP-2, MMP-9, and ADAMDEC1 expression levels may serve as potential diagnostic biomarkers for CRC.
ARTICLE INFORMATION
-
Conflict of interest
No potential conflict of interest relevant to this article was reported.
-
Funding
This study was financially supported by the Deputy of Research, Iran University of Medical Sciences (No. 22407).
-
Author contributions
Conceptualization: all authors; Data curation: all authors; Formal analysis: all authors; Funding acquisition: LB; Investigation: all authors; Writing–original draft: all authors; Writing–review & editing: all authors. All authors read and approved the final manuscript.
Supplementary materials
Supplementary materials are available from https://doi.org/10.3393/ac.2024.00227.0032.
Fig. 1.Serum matrix metalloproteinase 2 (MMP-2) and MMP-9 levels. (A) Differences in serum MMP-2 levels between colorectal cancer (CRC) and control groups. (B) Differences in serum MMP-9 levels between CRC and control groups. (C) Differences in serum MMP-2 levels between the lymphovascular invasion positive (LVI+) and LVI negative (LVI–) groups among patients with CRC. (D) Differences in serum MMP-9 levels between the LVI+ and LVI– groups among patients with CRC. ***P<0.001.
Fig. 2.Relative expression levels (−ΔCt) of (A) matrix metalloproteinase 2 (MMP-2), (B) MMP-9, and (C) a disintegrin and metalloproteinase like decysin 1 (ADAMDEC1) between the colorectal cancer (CRC) and control groups. Gene expression levels were normalized using β2 microglobulin as the housekeeping gene. Ct, cycle threshold. ***P<0.001.
Fig. 3.Potential diagnostic value of (A) matrix metalloproteinase 2 (MMP-2), (B) MMP-9, and (C) a disintegrin and metalloproteinase like decysin 1 (ADAMDEC1) in colorectal cancer. AUC, area under the curve.
Fig. 4.Relative expression levels (−ΔCt) of (A) matrix metalloproteinase 2 (MMP-2), (B) MMP-9, and (C) a disintegrin and metalloproteinase like decysin 1 (ADAMDEC1) between the lymphovascular invasion positive (LVI+) and LVI negative (LVI–) groups among patients with colorectal cancer. Gene expression levels were normalized using β2 microglobulin as the housekeeping gene. Ct, cycle threshold. ***P<0.001.
Table 1.Clinicopathological characteristics of patients
|
Characteristic |
No. of patients (n=100) |
|
Age (yr) |
|
|
≥45 |
54 |
|
<45 |
46 |
|
Sex |
|
|
Male |
48 |
|
Female |
52 |
|
TNM stage |
|
|
II |
29 |
|
III |
36 |
|
IV |
35 |
|
Tumor size (cm) |
|
|
<2 |
16 |
|
2–3.5 |
25 |
|
>3.5–5 |
21 |
|
>5 |
38 |
|
Tumor location |
|
|
Colon |
45 |
|
Rectum |
55 |
|
Lymphovascular invasion |
|
|
Positive |
40 |
|
Negative |
60 |
Table 2.Correlation analysis
|
Variable |
Serum MMP-2
|
Serum MMP-9
|
Tissue MMP-2
|
Tissue MMP-9
|
Tissue ADAMDEC1
|
Cancer stage
|
LVI
|
|
r |
95% CI |
P-value |
r |
95% CI |
P-value |
r |
95% CI |
P-value |
r |
95% CI |
P-value |
r |
95% CI |
P-value |
r |
95% CI |
P-value |
r |
95% CI |
P-value |
|
Serum MMP-2 |
- |
- |
- |
0.0671 |
−0.1368 to 0.2656 |
0.507 |
0.1267 |
−0.07730 to 0.3206 |
0.208 |
- |
- |
- |
- |
- |
- |
0.1388 |
−0.06505 to 0.3316 |
0.168 |
- |
- |
- |
|
Serum MMP-9 |
0.0671 |
−0.1368 to 0.2656 |
0.507 |
- |
- |
- |
- |
- |
- |
0.2166 |
0.01519 to 0.4011 |
0.030 |
- |
- |
- |
0.0937 |
−0.1104 to 0.2903 |
0.353 |
- |
- |
- |
|
Tissue MMP-2 |
- |
- |
- |
- |
- |
- |
- |
- |
- |
0.4028 |
0.2186 to 0.5594 |
<0.001 |
0.3771 |
0.1895 to 0.5382 |
0.001 |
0.2243 |
0.02326 to 0.4079 |
0.024 |
−0.4833 |
−0.6244 to −0.3117 |
<0.001 |
|
Tissue MMP-9 |
- |
- |
- |
- |
- |
- |
0.4028 |
0.2186 to 0.5594 |
<0.001 |
- |
- |
- |
0.5729 |
0.4194 to 0.6946 |
<0.001 |
0.2109 |
0.009249 to 0.3961 |
0.035 |
−0.7085 |
−0.7965 to −0.5910 |
<0.001 |
|
Tissue ADAMDEC1 |
- |
- |
- |
- |
- |
- |
0.3771 |
0.1895 to 0.5382 |
0.001 |
0.5729 |
0.4194 to 0.6946 |
<0.001 |
- |
- |
- |
0.3319 |
0.1391 to 0.5004 |
0.007 |
−0.7795 |
−0.8480 to −0.6854 |
<0.001 |
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