Diagnostic performance of dynamic contrast-enhanced magnetic resonance imaging parameters and serum tumor markers in rectal carcinoma prognosis

Abstract

BACKGROUND

Rectal carcinoma (RC), one of the most common malignancies globally, presents an increasing incidence and mortality year by year, especially among young people, which seriously affects the prognosis and quality of life of patients. At present, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters and serum carbohydrate antigen 19-9 (CA19-9) and CA125 Levels have been used in clinical practice to evaluate the T stage and differentiation of RC. However, the accuracy of these evaluation modalities still needs further research. This study explores the application and value of these methods in evaluating the T stage and differentiation degree of RC.

AIM

To analyze the diagnostic performance of DCE-MRI parameters combined with serum tumor markers (TMs) in assessing pathological processes and prognosis of RC patients.

METHODS

A retrospective analysis was performed on 104 RC patients treated at Yantai Yuhuangding Hospital from May 2018 to January 2022. Patients were categorized into stages T1, T2, T3, and T4, depending on their T stage and differentiation degree. In addition, they were assigned to low (L group) and moderate-high differentiation (M + H group) groups based on their differentiation degree. The levels of DCE-MRI parameters and serum CA19-9 and CA125 in different groups of patients were compared. In addition, the value of DCE-MRI parameters [volume transfer constant (Ktrans), rate constant (Kep), and extravascular extracellular volume fraction (Ve) in assessing the differentiation and T staging of RC patients was discussed. Furthermore, the usefulness of DCE-MRI parameters combined with serum CA19-9 and CA125 Levels in the evaluation of RC differentiation and T staging was analyzed.

RESULTS

Ktrans, Ve, CA19-9 and CA125 were higher in the high-stage group and L group than in the low-stage group and M + H Group, respectively (P < 0.05). The areas under the curve (AUCs) of the Ktran and Ve parameters were 0.638 and 0.694 in the diagnosis of high and low stages, respectively, and 0.672 and 0.725 in diagnosing moderate-high and low differentiation, respectively. The AUC of DCE-MRI parameters (Ktrans + Ve) in the diagnosis of high and low stages was 0.742, and the AUC in diagnosing moderate-high and low differentiation was 0.769. The AUCs of CA19-9 and CA-125 were 0.773 and 0.802 in the diagnosis of high and low stages, respectively, and 0.834 and 0.796 in diagnosing moderate-high and low differentiation, respectively. Then, we combined DCE-MRI (Ktrans + Ve) parameters with CA19-9 and CA-125 and found that the AUC of DCE-MRI parameters plus serum TMs was 0.836 in the diagnosis of high and low stages and 0.946 in the diagnosis of moderate-high and low differentiation. According to the Delong test, the AUC of DCE-MRI parameters plus serum TMs increased significantly compared with serum TMs alone in the diagnosis of T stage and differentiation degree (P < 0.001).

CONCLUSION

The levels of the DCE-MRI parameters Ktrans and Ve and the serum TMs CA19-9 and CA125 all increase with increasing T stage and decreasing differentiation degree of RC and can be used as indices to evaluate the differentiation degree of RC in clinical practice. Moreover, the combined evaluation of the above indices has a better effect and more obvious clinical value, providing important guiding importance for clinical condition judgment and treatment selection.

Key Words: Rectal carcinoma, Volume transfer constant, Rate constant, Extravascular extracellular volume fraction, Serum carbohydrate antigen 19-9, Serum carbohydrate antigen 125

Core Tip: This study explored the application and value of dynamic contrast-enhanced magnetic resonance imaging parameters and serum carbohydrate antigen 19-9 (CA19-9) and CA125 Levels in evaluating the T stage and differentiation degree of rectal carcinoma (RC). The results show that these assessment tools have significant predictive ability and may improve the diagnostic accuracy of RC. In addition, our research highlights the importance of a deeper understanding of the biological characteristics and disease progression of RC. The comprehensive use of these tools can help doctors provide more personalized treatment programs for patients and improve patient outcomes.

INTRODUCTION

The latest statistics from the World Health Organization (WHO) reveal that there were approximately 19.3 million new cancer cases diagnosed globally in 2020, of which colorectal carcinoma (CRC) accounted for more than 1.9 million, indicating that one out of every ten new cancer cases was CRC[1]. By 2021, the incidence and mortality of CRC have climbed to third and second place in the global cancer rankings, respectively, and it is worth noting that rectal carcinoma (RC) cases account for approximately 40% of the total CRC cases[2]. In China, the prevalence of RC is rising constantly, while the age of onset is gradually decreasing[3]. Early-stage RC is often atypical and difficult to detect, and the prognosis of patients is usually grim when there are middle and late symptoms such as hematochezia and abdominal pain[4]. Early detection, diagnosis and treatment of RC is therefore key to improving survival and quality of life.

Doctors will choose appropriate treatment strategies, such as local lesion excision, radical surgical resection, and preoperative neoadjuvant chemoradiotherapy, depending on the stages and grades of the patients' tumors[5]. According to the National Comprehensive Cancer Network clinical practice guidelines for RC and National Guidelines for the Diagnosis and Treatment of Colorectal Cancer in China (2020 Edition)[6], early RC (T1-T2N0) is usually treated with endoscopic resection, local resection or radical surgical resection. For those with locally advanced T3-T4 RC and/or N+ resectable RC, neoadjuvant chemoradiotherapy is recommended to shrink the focus and downgrade the tumor before radical surgery. In addition, RC can be classified into high-, moderate-, and low-differentiation as well as undifferentiated, according to cancer cell differentiation. These different histopathological differentiation degrees have significant variations in biological characteristics, which may be characterized by slow growth or widespread metastasis and rapid growth[7]. Currently, patients' pathological grades are mostly determined by biopsy. However, when diagnosed, many of them miss out on the best chance of treatment. Hence, early diagnosis, determination of pathological grades as soon as possible, and selection of appropriate treatment strategies are of great importance for improving survival and prognosis[8,9]. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can display blood perfusion at the tissue capillary level, enable in vivo evaluation of tumor microcirculation perfusion, and be used to quantitatively evaluate the benign and malignant degree of tumors[10,11]. Tumor markers (TMs) are biochemical substances secreted by malignant tumor cells in the process of proliferation that have certain biological characteristics and are commonly used in early diagnosis and prognosis prediction. Research[4] shows that serum carbohydrate antigen (CA) 19-9 and CA125 Levels can reflect the characteristics of primary tumors to a certain extent and play an important role in tumor cell metastasis and invasion[12]. However, there are limited studies on using DCE-MRI parameters combined with serum CA19-9 and CA125 Levels to evaluate the differentiation degree and T stage of RC patients, although it is an area worthy of in-depth discussion.

Accordingly, 129 RC patients with different degrees of tumor differentiation were selected and subjected to DCE-MRI and serum CA19-9 and CA125 detection to explore the evaluation value of these indices on the degree of tumor differentiation.

MATERIALS AND METHODS

Sample source

This retrospective study comprised 184 RC patients who were enrolled between May 2018 and January 2022.

Eligibility and exclusion criteria

The eligibility criteria were as follows: (1) Meeting the relevant diagnostic criteria for RC with confirmed diagnosis after pathological examination, including histopathology, gross pathological specimens and immunohistochemistry; (2) receiving preoperative examination by magnetic resonance imaging (MRI); and (3) normal language communication skills and active cooperation with the study.

The exclusion criteria were as follows: (1) Serious diseases of the heart, kidney, liver, lungs or other vital organs; (2) hematological diseases; (3) use of tumor-related treatment, such as radiotherapy and chemotherapy, before presentation; (4) patients whose largest tumor diameter was less than 1 cm or whose rectal peristalsis amplitude was too large to be accurately measured; (5) poor DCE-MRI image quality or artifacts affecting data measurement; or (6) pregnant and lactating patients.

Sample screening

A total of 104 eligible patients were screened according to the above eligibility and exclusion criteria. Based on T staging, patients with T1/2 and T3/4 RC were assigned to the low stage group and high stage group, respectively. In addition, they were divided into low (L group) and moderate-high (M + H group) differentiation groups based on their differentiation degree.

MRI inspection and image analysis and processing

In this study, a Siemens (Germany) Skyra 3-T MRI scanner and abdominal phased-array coil were used for inspection. All patients abstained from food and water for 4 h prior to examination. MRI scans included conventional axial T1-weighted imaging (T1WI), axial, coronal and sagittal T2-weighted imaging (T2WI), and axial diffusion-weighted imaging. DCE scanning involved a T1 three-dimensional volume interpolated breath-hold examination sequence with the same scanning planes as the T2WI scans. The parameters of DCE-MRI scanning included a field of view of 260 mm, repetition time of 5.08 ms, echo time of 1.77 ms, matrix of 154 × 192, layer thickness of 3.5 mm, flip angle of 15°, and number of excitations of 1. The contrast agent was Gd-DTPA, which was injected through the elbow vein at a flow rate of 3 mL/s with a dose of 0.1 mmol/kg. Then, 35 consecutive phases were scanned, each with a scanning time of 8 s, allowing the patient to breathe freely. The contrast agent was injected at the third phase with a total dose of 15-20 mL, covering the whole tumor, and the scanning time was 280 s. After contrast injection, 20 mL of normal saline was flushed down the pipeline at the same flow rate. After that, all the raw images were transmitted to the Siemens postprocessing workstation, and DCE-MRI data were analyzed using Tissue 4D software.

Two MRI diagnosticians with more than 5 years of experience read the DCE-MRI images without understanding the pathological findings of the patients. Three circular or elliptical regions of interest (ROIs) were selected in the areas with obvious tumor parenchyma enhancement. The ROIs were as uniform in size as possible, covering the parenchyma of the lesion, with an area greater than 1/3 of the lesion parenchyma, and avoiding the necrotic area and cystic change area of the tumor. Parameters such as the volume transfer constant (Ktrans), rate constant (Kep), and extravascular extracellular volume fraction (Ve) were analyzed using a three-compartment pharmacokinetic model (Tofts model).

Detection of TMs

For TM detection, 4 mL of fasting venous blood was taken from all patients in the morning and centrifuged for 10 minutes (3000 r/min) to separate CA19-9 and CA125 measurements with a Liaison XL type 2210 automatic electrochemiluminescence analyzer from DiaSorin Company in Italy. The operation was performed according to the kit instructions.

Outcome measures

The levels of DCE-MRI parameters and the expression of serum CA19-9 and CA125 were comparatively analyzed. The values of DCE-MRI parameters (Ktrans, Kep, and Ve) in the diagnosis of differentiation degree and T staging of RC patients were analyzed. The performance of DCE-MRI parameters combined with serum CA19-9 and CA125 Levels for the diagnosis of differentiation and T-staging of RC patients was discussed.

Statistical analysis

This study employed SPSS 26.0 for data processing. Continuous variables, represented by means, were analyzed with the t test. Categorical variables were expressed by n (%) and tested by χ². The role of DCE-MRI parameters and serum CA19-9 and CA125 Levels in the evaluation of differentiation and T staging of RC patients was analyzed using receiver operating characteristic (ROC) curves. The difference in the ROC curves of these indicators was analyzed using the Delong test.

RESULTS

Baseline data

In this part of the study, we conducted a comprehensive comparison of clinical data among patients. Our analysis encompassed various factors, including age, sex, body mass index, tumor location, and tumor type. The patient pool was categorized into two groups for comparison: the low- and high-stage groups, and the M + H and L groups. The results indicated no significant differences in these clinical parameters between the groups (P > 0.05, Tables 1 and 2). This suggests that these factors do not vary significantly with the stage or differentiation degree of rectal cancer in our patient cohort.

Table 1 Comparison of baseline data of rectal carcinoma patients with different T stages.

Factors	Low stage group (n = 62)	High stage group (n = 42)	P value
Age (yr)			0.474
≥ 60	34	26
< 60	28	16
Sex			0.636
Male	34	25
Female	28	17
BMI (kg/m2)			0.755
≥ 25	16	12
< 25	46	30
Tumor site			0.991
Upper	21	14
Middle	17	12
Lower	24	16
Tumor type			0.854
Protruded	8	7
Ulcerative	44	29
Infiltrating	10	6
Differentiation degree			0.786
Moderate-high differentiation	40	26
Low differentiation	22	16

BMI: Body mass index.

Table 2 Comparison of baseline data of patients with different differentiation degrees.

Factors	M + H group (n = 66)	L group (n = 38)	P value
Age (yr)			0.703
≥ 60	39	21
< 60	27	17
Sex			0.855
Male	37	22
Female	29	16
BMI (kg/m2)			0.572
≥ 25	19	9
< 25	47	29
Tumor site			1.069
Upper	23	12
Middle	20	9
Lower	23	17
Tumor type			0.797
Protruded	10	5
Ulcerative	47	26
Infiltrating	9	7
T staging			0.786
T1-T2	40	22
T3-T4	26	16

M+H: Modern + high; L: Low; BMI: Body mass index.

Levels of DCE-MRI parameters and TMs in patients with different T stages

Our study further explored the levels of DCE-MRI parameters and TMs – specifically Ktrans, Ve, CA19-9, and CA125 – between the low and high tumor stage groups. Notably, Ktrans, Ve, CA19-9, and CA125 levels were significantly higher in patients with advanced tumor stages (P < 0.05; Figure 1). This finding was intriguing, as it suggests these markers' potential in indicating tumor stage. However, Kep levels did not show a significant difference between these groups (P > 0.05; Figure 1), indicating its limited utility in distinguishing between low and high tumor stages.

Figure 1 Levels of dynamic contrast-enhanced magnetic resonance imaging parameters and tumor markers in different T stages. A: Comparison of volume transfer constant between low and high stage groups; B: Comparison of rate constant between low and high stage groups; C: Comparison of extravascular extracellular volume fraction between low and high stage groups; D: Comparison of carbohydrate antigen 19-9 (CA19-9) between low and high stage groups; E: Comparison of CA125 between low and high stage groups. Ktrans: Volume transfer constant; Kep: Rate constant; Ve: Extravascular extracellular volume fraction; CA19-9: Carbohydrate antigen 199; CA12-5: Carbohydrate antigen 125.

Levels of DCE-MRI parameters and TMs in patients with different differentiation degrees

In this section, we compared the same DCE-MRI parameters and TMs between the L and M + H groups. The results were somewhat unexpected: Ktrans, Ve, CA19-9, and CA125 Levels were higher in the L group compared to the M + H group (P < 0.05; Figure 2). The similarity in Kep levels between these groups (P > 0.05; Figure 2) mirrored the findings from the tumor stage comparison, reinforcing Kep's limited differentiating ability.

Figure 2 Levels of dynamic contrast-enhanced magnetic resonance imaging parameters and tumor markers in different differentiation degrees. A: Comparison of volume transfer constant between low (L) and moderate + high (M + H) groups; B: Comparison of rate constant between L and M + H groups; C: Comparison of extravascular extracellular volume fraction between L and M + H groups; D: Comparison of carbohydrate antigen 19-9 (CA19-9) between L and M + H groups; E: Comparison of CA125 between L and M + H groups. M + H: Moderate + high; L: Low; Ktrans: Volume transfer constant; Kep: Rate constant; Ve: Extravascular extracellular volume fraction; CA19-9: Carbohydrate antigen 199; CA12-5: Carbohydrate antigen 125.

Value of DCE-MRI parameters in the diagnosis of T stage and differentiation degree

In the above study, we confirmed a connection between the DCE-MRI parameters Ktran and Ve and the T stage and differentiation degree in RC patients. To determine the diagnostic value of Ktran and Ve in T staging and differentiation degree, we analyzed their ROC curves. The areas under the curve (AUCs) of Ktran and Ve for diagnosing high and low tumor stages were 0.638 and 0.694, respectively, and those for diagnosing moderate-high and low differentiation were 0.672 and 0.725, respectively. In addition, we combined Ktran and Ve for diagnosis. Through plotting ROC curves, it was found that the AUC of Ktrans + Ve was 0.742 for diagnosing high and low stages and 0.769 for diagnosing moderate-high and low differentiation (Figure 3 and Table 3).

Figure 3 The areas under the curve of dynamic contrast-enhanced magnetic resonance imaging parameters for the diagnosis of T stage and differentiation degree. A: The areas under the curve (AUC) of volume transfer constant (Ktran) in the diagnosis of high and low stages; B: The AUC of extravascular extracellular volume fraction (Ve) in the diagnosis of high and low stages; C: The AUC of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters in the diagnosis of high and low stages; D: The AUC of Ktran in the diagnosis of moderate-high and low differentiation; E: The AUC of Ve in the diagnosis of moderate-high and low differentiation; F: The AUC of DCE-MRI parameters in the diagnosis of moderate-high and low differentiation. Ktrans: Volume transfer constant; Kep: Rate constant; Ve: Extravascular extracellular volume fraction; DCE-MRI: Dynamic contrast-enhanced magnetic resonance imaging.

Table 3 Receiver operating characteristic curve analysis of various parameters.

Diagnostic variable	AUC	95%CI	Cut-off	Sensitivity	Specificity	Youden index
T stage
Ktrans	0.638	0.532-0.745	0.26	62.90%	59.52%	22.43%
Ve	0.695	0.595-0.794	0.45	40.32%	92.86%	33.18%
DCE-MRI parameters	0.742	0.646-0.837	0.68	53.23%	92.86%	46.08%
Differentiation degree
Ktrans	0.672	0.549-0.795	0.29	87.88%	57.90%	45.77%
Ve	0.725	0.626-0.824	0.49	75.76%	63.16%	38.92%
DCE-MRI parameters	0.769	0.677-0.861	0.35	78.79%	65.79%	44.58%

AUC: Area under the curve; Ktrans: Volume transfer constant; Ve: Extravascular extracellular volume fraction; DCE-MRI: Dynamic contrast-enhanced magnetic resonance imaging.

Diagnostic performance of DCE-MRI parameters (Ktrans + Ve) plus TMs for T stage and differentiation

In this section, we studied the diagnostic performance of TMs for T stage and differentiation. Through analysis, it was found that the AUCs of CA19-9 and CA-125 in the diagnosis of high and low stages were 0.773 and 0.802, respectively, while those in the diagnosis of moderate-high differentiation and low differentiation were 0.834 and 0.796, respectively. Then, we combined DCE-MRI parameters (Ktrans + Ve) with CA19-9 and CA-125 for detection and found that the AUC of DCE-MRI parameters plus TMs was 0.836 in the diagnosis of high and low stages and 0.946 in diagnosing moderate-high differentiation and low differentiation (Figure 4 and Table 4). In addition, through the Delong test analysis, it was found that the AUC of DCE-MRI parameters + TMs increased significantly compared with TMs alone in the diagnosis of T stage and differentiation degree (P < 0.001; Table 5).

Figure 4 The areas under the curve of dynamic contrast-enhanced magnetic resonance imaging parameters, carbohydrate antigen 19-9 and carbohydrate antigen 125 for the diagnosis of T stage and differentiation degree. A: The areas under the curve (AUC) of carbohydrate antigen 19-9 (CA19-9) in the diagnosis of high and low stages; B: The AUC of CA125 in the diagnosis of high and low stages; C: The AUC of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters plus tumor markers in the diagnosis of high and low stages; D: The AUC of CA19-9 in the diagnosis of moderate-high and low differentiation; E: The AUC of CA19-9 in the diagnosis of moderate-high and low differentiation; F: The AUC of DCE-MRI parameters plus tumor markers in the diagnosis of moderate-high and low differentiation. CA19-9: Carbohydrate antigen 199; CA125: Carbohydrate antigen 125; DCE-MRI: Dynamic contrast-enhanced magnetic resonance imaging.

Table 4 Receiver operating characteristic curve analysis of various parameters.

Diagnostic variable	AUC	95%CI	Cut-off	Sensitivity	Specificity	Youden index
T stage
CA19-9	0.773	0.684-0.863	23.63	53.23%	100.00%	53.23%
CA125	0.802	0.716-0.888	66.90	67.74%	90.48%	58.22%
DCE-MRI parameters + tumor markers	0.836	0.756-0.916	0.93	72.58%	95.24%	67.82%
Differentiation degree
CA19-9	0.834	0.758-0.909	27.49	81.82%	68.42%	50.24%
CA125	0.796	0.711-0.881	66.82	62.12%	89.47%	51.60%
DCE-MRI parameters + tumor markers	0.946	0.903-0.990	0.76	87.88%	97.37%	85.25%

AUC: Area under the curve; DCE-MRI: Dynamic contrast-enhanced magnetic resonance imaging; CA19-9: Carbohydrate antigen 19-9; CA125: Carbohydrate antigen 125.

Table 5 Delong test of the areas under the curve of DCE-MRI parameters and tumor markers in distinguishing T staging and differentiated degree.

Test results	Z value	P value	Difference in AUC	Standard error difference	95%CI
					Lower bound	Upper bound
T stage
CA199-CA125	-1.452	0.146	-0.029	0.293	-0.068	0.01
CA199 - DCE-MRI parameters + tumor markers	7.616	< 0.001	0.609	0.299	0.453	0.766
CA125- DCE-MRI parameters + tumor markers	7.856	< 0.001	0.638	0.296	0.479	0.797
Differentiation degree
CA199-CA125	0.617	0.537	0.038	0.287	-0.082	0.157
CA199- DCE-MRI parameters + tumor markers	14.913	< 0.001	0.780	0.248	0.677	0.882
CA125- DCE-MRI parameters + tumor markers	13.382	< 0.001	0.742	0.257	0.633	0.851

AUC: Area under the curve; DCE-MRI: Dynamic contrast-enhanced magnetic resonance imaging; CA19-9: Carbohydrate antigen 19-9; CA125: Carbohydrate antigen 125.

DISCUSSION

RC is the third most prevalent digestive system malignancy worldwide and the fourth most deadly of all malignancies[13]. It shows increasing morbidity and mortality and a rising incidence at younger ages, thereby having an enormous negative impact on people's prognosis and quality of life[14]. Tumor angiogenesis, the growth basis of RC, is also related to tumor pathological differentiation. The lower the tumor differentiation degree, the higher the heterogeneity, the more common mitotic figures and pathological mitotic figures, and the higher the degree of malignancy. Due to the low accuracy of the early diagnosis of RC, most patients have reached the advanced stage at the time of diagnosis, leading to poor prognoses[15]. In addition, according to the 2011 National Comprehensive Cancer Network guidelines, all patients with stage T3 or lymph node-positive RC of any T stage should receive preoperative neoadjuvant therapy[16]. Therefore, accurate evaluation of the tumor focus of RC, including T stage and differentiation degree, can provide an objective basis for clinicians to choose treatment plans and evaluate the prognosis of patients.

DCE-MRI is an imaging modality superior to conventional modalities, which enables accurate and quantitative assessment of the T stage and differentiation of RC prior to surgery by combining morphological and hemodynamic changes[17]. One of the methods commonly used in early diagnosis involves detection of TMs, among which CA19-9 and CA125 are often used in the diagnosis of digestive system malignancies. The abnormal expression of these markers can reflect the degree of pathological changes and malignant transformation of cells, which can be used for tumor differentiation evaluation[18]. To better guide clinical work, this study involved using a joint assessment of DCE-MRI parameters and serum CA19-9 and CA125 Levels to assess the T stage and differentiation degree of RC. In the study, Ktrans and Ve values were found to be lower in patients in the M + H group than in the L group, suggesting that DCE-MRI parameters can reflect microcirculation differences in RC. DCE-MRI quantitative analysis can be used to quantify the contrast agent exchange between intercellular spaces and blood vessels in tissues, which reflects tissue perfusion and vascular endothelial integrity[19,20]. Ktrans represents the contrast dose per unit volume of tissue from blood into the extravascular extracellular space and is therefore related to the angiogenic activity and aggressiveness of the tumor; its magnitude depends on the surface area of the vascular endothelium, permeability, and the amount of blood passing through the tissue[21,22]. The Ve value represents the volume of extravascular extracellular space per unit volume of tissue and reflects the degree of histocellular cellularization and tissue necrosis of ROIs. The Ve value is positively associated with the volume of extracellular space, indicating a greater degree of tissue necrosis or a lower degree of cellularization[22]. Kep represents the contrast dose that penetrates into the blood vessels from the extravascular extracellular space per unit time, and its magnitude depends mainly on the permeability of the capillaries, reflecting the growth state of the tumor microvessels[22]. We believe that the malignant degree of RC gradually increases as the differentiation degree of the patient's tumor decreases and the T-stage increases; along with enhanced local neovascularization and blood perfusion, stimulation of vascular endothelial growth factor on blood vessels increases, as does vascular permeability, making it easier for plasma contrast agents to be extravasated, triggering an increase in Ktrans value, promoting the change of extracellular matrix and the increase of extracellular space, and leading to an increase in Ve value. Kep is related to the components in the extracellular space of tissues. Although the local microvascular permeability of cancer tissue is high, the components in the extracellular space of lesions with different stages and degrees of differentiation are relatively small. Previous studies have also found that Ktrans and Ve are significantly lower in patients with stage T1-T2 disease than in those with stage T3a disease, and both have an AUC greater than 0.6 in distinguishing the two groups of patients[23]. In addition, in another study, the difference between the T-stage of tumors and the quantitative parameter Kep value was not statistically significant, consistent with our findings[24]. Through ROC curve analysis, it was found that various DCE-MRI parameters had definite value in evaluating the T stage and differentiation degree of RC, and the combined application of DCE-MRI parameters can balance the difference between the specificity and sensitivity of these parameters when used alone. This also suggests that the combined detection by DCE-MRI parameters has higher evaluation value, which may be because each parameter of DCE-MRI reflects the abnormalities of tumor microvascular structure and function in different ways, and the combined application is helpful to reduce missed diagnosis and misdiagnosis, improving the evaluation value.

We also observed lower serum CA19-9 and CA125 Levels in the M + H group than in the L group and also in the low-stage group compared to the high-stage group, suggesting that as the T stage of the tumor increases and the degree of differentiation decreases, the levels of these TMs increase accordingly. TMs are specific substances produced and released by tumor cells. The lower the degree of tumor differentiation, the higher the malignancy degree and the higher the proliferative activity of tumor cells, resulting in a corresponding increase in the levels of TMs. CA19-9 is a mucin-type carbohydrate protein extracted from human colon cancer cells. As a nonspecific tumor-associated antigen, it is mainly present in the fetal gastrointestinal tract and pancreatic epithelial tissue. CA19-9 is expressed at a very low level in normal humans, and its high levels may indicate a high degree of malignancy, so it is often used as an auxiliary diagnostic indicator for malignancy[25,26]. CA125 is a high molecular weight glycoprotein, a mucin-like glycoprotein complex, presenting lower concentrations in serum in healthy adults but significantly elevated levels in gastrointestinal malignancies[27]. The above results indicate that serum CA19-9 and CA125 levels can be used to judge the malignant degree of RC, and the tumor malignant degree is closely related to T stage and differentiation degree. Therefore, it is inferred that serum CA125 expression is obviously different in RCs with different T stages and differentiation degrees and increases with increasing T stage and decreasing differentiation degree.

Finally, we evaluated the diagnostic value of TMs and DCE-MRI parameters in T staging and differentiation. The TMs CA19-9 and CA125 were analyzed first. Through ROC curve analysis, it was found that the sensitivity of the two was low when they were used alone in evaluating the T stage and differentiation of RC, but when combined with DCE-MRI parameters, the sensitivity of CA19-9 and CA125 reached 72.58% and 87.88%, respectively. This shows that combined detection can significantly improve the sensitivity of TMs in evaluating the differentiation degree of RC, which is helpful for assessing RC at an early stage and guiding clinical treatment. We believe that this is because DCE-MRI parameters can help clinicians understand the differentiation degree of RC from the imaging point of view, while serum CA19-9 and CA125 reflect the differentiation degree of RC from the perspective of biochemistry. They complement each other and using them can reduce missed diagnoses and misdiagnoses.

However, there are some limitations in this study. First, as a retrospective study, there is inevitable selection bias. Second, the image acquisition and postprocessing are not standardized and involve some subjective factors, which are easily biased and cannot truly reflect the blood flow situation of the tumor parenchyma. For example, the results may vary depending on the ROIs chosen. It is hoped that future research on the quantitative parameters of DCE-MRI will achieve gratifying results so that the diagnosis and treatment of RC will enter a new era.

CONCLUSION

The DCE-MRI parameters Ktrans and Ve as well as the serum levels of the TMs CA19-9 and CA125 all increased with increasing T stage and decreasing differentiation degree of RC. These indices can be used as important markers to evaluate the differentiation degree of RC, especially when they are jointly evaluated, playing a superior role with more obvious clinical value. These indices have substantial guiding importance for clinical diagnosis and treatment selection.

ARTICLE HIGHLIGHTS

Research background

Rectal carcinoma (RC) is a globally prevalent fatal tumor, and its early diagnosis and staging are crucial. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters and serum levels of carbohydrate antigen 19-9 (CA19-9) and CA125 have shown potential diagnostic value in many diseases, but their roles in the assessment of T stage and degree of differentiation in RC remain unclear.

Research motivation

The motivation of this study is to clarify the effectiveness of DCE-MRI parameters and serum levels of CA19-9 and CA125 in assessing the T stage and degree of differentiation in RC. We hope that through this study, we can provide clinicians with a reliable tool for more accurate diagnosis and treatment of RC.

Research objectives

The objective of this study was to investigate the application of DCE-MRI parameters and serum levels of CA19-9 and CA125 in evaluating the T stage and degree of differentiation of RC to improve the diagnostic accuracy and treatment effect of RC.

Research methods

We conducted a retrospective study on eligible patients with RC and collected and analyzed the DCE-MRI parameters and serum levels of CA19-9 and CA125. We then evaluated their predictive ability for T stage and degree of differentiation of RC using statistical models.

Research results

Our research results show that DCE-MRI parameters and serum levels of CA19-9 and CA125 have significant predictive abilities and may improve RC-related diagnostic accuracy.

Research conclusions

DCE-MRI parameters and serum levels of CA19-9 and CA125 have significant value in assessing the T stage and degree of differentiation of RC and can be used to help physicians provide more personalized treatment plans, improving patient prognosis.

Research perspectives

Future research might further explore the application of these tools in a broader cohort of patients with RC as well as how they could be combined with other potential biomarkers and imaging parameters to provide a more comprehensive framework for RC assessment.