Results
Comparison of the general situation of research subjects
A total of 135 people made up the control group, and 296 people with colonic neoplasms were included in this retrospective analysis. Regarding age, BMI, gender, ALT, AST, and TC, there was no statistically significant difference (P > 0.05) between the two groups, suggesting comparability (Table 1).
Table 1Comparison of general conditions between the colonic neoplasms group and the control group
General information | Colonic neoplasms group (n = 296) | Control group (n = 135) | P value |
---|
Age (year) | 56.82 ± 8.74 | 55.35 ± 8.79 | 0.107 |
BMI (kg/m2) | 23.98 ± 2.44 | 23.52 ± 2.37 | 0.068 |
Gender, n (%) | | | 0.088 |
Males | 160 (54.05%) | 61 (45.19%) | |
Females | 136 (45.95%) | 74 (54.81%) | |
ALT (U/L) | 17.00 (13.00, 24.75) | 17.00 (13.00, 24.00) | 0.853 |
AST (U/L) | 20.00 (16.00, 24.00) | 19.00 (16.00, 23.00) | 0.351 |
TC (mmol/L) | 4.38 ± 0.88 | 4.56 ± 0.91 | 0.062 |
Comparison of serum BA compositions between colonic neoplasms group and control group
There was a statistical difference between the two groups in TCA, GCDCA, TCDCA, and DCA (P < 0.05). While the content of DCA was lower than that of the control group, the content of TCA, GCDCA, and TCDCA was significantly higher in the colonic neoplasms group. There was no statistical difference (P > 0.05) in the other BA components between the two groups, as shown in Table 2.
Table 2Detection results of serum BA profiles in the colonic neoplasms group and the control group (nmol /L)
BA components | Colonic neoplasms group (n = 204) | Control group (n = 135) | P value |
---|
Primary free BAs | | | |
CA | 65.60 (24.83, 234.00) | 53.80 (27.60, 149.00) | 0.362 |
CDCA | 373.50 (94.90, 851.50) | 294.00 (130.00, 625.00) | 0.274 |
Primary conjugated BAs | | | |
TCA | 22.40 (5.80, 51.78) | 12.70 (1.50, 32.30) | 0.007* |
GCA | 159.00 (69.15, 321.75) | 126.00 (52.90, 234.00) | 0.057 |
GCDCA | 900.00 (428.25, 1,810.00) | 708.00 (298.00, 1,250.00) | 0.008* |
TCDCA | 72.45 (27.15, 158.00) | 41.60 (18.30, 119.00) | 0.006* |
Secondary free BAs | | | |
DCA | 146.00 (19.63, 434.00) | 234.00 (82.60, 502.00) | 0.009* |
LCA | 8.10 (0.40, 23.03) | 6.40 (0.60, 21.00) | 0.841 |
UDCA | 67.50 (19.58, 230.75) | 70.70 (19.00, 199.00) | 0.802 |
Secondary conjugated BAs | | | |
TDCA | 8.15 (0.00, 30.05) | 7.70 (0.00, 35.30) | 0.827 |
GDCA | 117.50 (11.90, 267.75) | 125.00 (34.60, 335.00) | 0.332 |
TLCA | 0.15 (0.00, 2.48) | 0.10 (0.00, 4.00) | 0.299 |
GLCA | 4.20 (0.00, 15.65) | 5.40 (0.00, 18.10) | 0.295 |
TUDCA | 7.85 (3.325, 15.00) | 8.20 (2.50, 15.00) | 0.458 |
GUDCA | 107.50 (42.78, 330.50) | 122.00 (63.80, 283.00) | 0.825 |
Comparison of serum BA profiles in patients with different pathological types of colonic neoplasms
For subgroup analysis, individuals with colonic neoplasms were categorized into three groups based on their pathological types: the non-adenomatous polyp group (59 cases), the adenomatous polyp group (145 cases), and the colonic cancer group (92 cases). As indicated in Table 3, there was no statistical difference in the compositions of BAs across the groups, except for statistical differences in CA (P = 0.011), UDCA (P = 0.009), and GUDCA (P = 0.050) among the various pathological types of colonic neoplasms. The content of CA was higher in non-adenomatous polyp group than in adenomatous polyp group (P = 0.010); the content of GUDCA was higher in non-adenomatous polyp group than in colonic cancer group (P = 0.044); the content of UDCA was higher in non-adenomatous polyp group than in adenomatous polyp group (P = 0.011); and the content of UDCA was higher in non-adenomatous polyp group than in colonic cancer group (P = 0.022). These findings were obtained through paired analysis on indicators with statistically significant differences.
Table 3Comparison of BA differences in different pathological types of colonic neoplasms (nmol/L)
BA components | Non-adenomatous polyp group (n = 59) | Adenomatous polyp group (n = 145) | Colonic cancer group (n = 92) | H value | P value |
---|
Primary free BAs | | | | | |
CA | 107.00 (39.50, 357.00) | 53.20 (20.35, 185.50) | 104.15 (26.60, 286.50) | 9.075 | 0.011* |
CDCA | 408.00 (191.00, 1,130.00) | 373.00 (80.50, 785.00) | 298.50 (65.55, 999.75) | 5.035 | 0.081 |
Primary conjugated BAs | | | | | |
TCA | 24.80 (8.90, 71.50) | 20.10 (5.45, 45.80) | 24.85 (7.50, 58.25) | 1.937 | 0.380 |
GCA | 160.00 (81.70, 423.00) | 174.00 (72.60, 326.00) | 132.50 (59.40, 283.75) | 1.539 | 0.463 |
GCDCA | 866.00 (458.00, 2,190.00) | 961.00 (397.00, 1,785.00) | 828.50 (409.50, 1,455.00) | 1.560 | 0.458 |
TCDCA | 113.00 (40.70, 185.00) | 64.50 (24.60, 152.50) | 70.65 (27.15, 132.25) | 4.231 | 0.121 |
Secondary free BAs | | | | | |
DCA | 182.00 (38.50, 448.00) | 118.00 (21.25, 401.00) | 165.00 (7.18, 468.00) | 1.208 | 0.547 |
LCA | 5.30 (0.00, 16.80) | 6.70 (0.50, 17.20) | 12.65 (0.40, 26.83) | 5.257 | 0.072 |
UDCA | 107.00 (49.00, 311.00) | 64.00 (16.15, 190.00) | 50.00 (16.18, 238.25) | 9.453 | 0.009* |
Secondary conjugated BAs | | | | | |
TDCA | 17.90 (2.50, 39.10) | 6.80 (0.00, 24.35) | 7.95 (0.00, 26.63) | 3.763 | 0.152 |
GDCA | 135.00 (7.40, 398.00) | 107.00 (19.25, 229.00) | 132.50 (10.33, 353.00) | 0.515 | 0.773 |
TLCA | 0.00 (0.00, 2.10) | 0.00 (0.00, 2.55) | 0.50 (0.00, 2.68) | 0.675 | 0.714 |
GLCA | 4.40 (0.00, 20.30) | 4.60 (0.00, 15.50) | 3.90 (0.00, 13.58) | 0.365 | 0.833 |
TUDCA | 11.70 (4.50, 20.10) | 6.50 (2.95, 15.00) | 8.25 (3.50, 15.00) | 5.398 | 0.067 |
GUDCA | 220.00 (58.10, 543.00) | 114.00 (43.55, 303.00) | 81.65 (35.63, 280.75) | 5.994 | 0.050* |
Correlation analysis between serum BA profile levels and clinical pathological parameters of colonic neoplasms
As demonstrated in Table 4, no significant correlation was found between the levels of various serum BA profile components and tumor size within the colonic neoplasms group when these variables were analyzed using Spearman correlation analysis. However, there was a negative correlation between neoplasm pathological type and the content of CDCA (r = −0.121, P = 0.038) and GUDCA (r = −0.149, P = 0.010).
Table 4Correlation analysis between serum BA profiles levels and clinical pathological parameters of colonic neoplasms
BA components | Size of tumor
| Pathological type
|
---|
r value | P value | r value | P value |
---|
CA | 0.011 | 0.852 | −0.028 | 0.636 |
CDCA | −0.032 | 0.580 | −0.121 | 0.038 |
DCA | 0.008 | 0.891 | −0.067 | 0.251 |
LCA | 0.072 | 0.217 | 0.069 | 0.237 |
UDCA | 0.030 | 0.602 | −0.112 | 0.055 |
GCA | −1.000 | 0.085 | 0.025 | 0.672 |
GCDCA | −0.062 | 0.285 | −0.050 | 0.394 |
GDCA | 0.014 | 0.806 | −0.034 | 0.557 |
GLCA | −0.024 | 0.680 | −0.034 | 0.555 |
GUDCA | −0.015 | 0.797 | −0.149 | 0.010 |
TCA | 0.006 | 0.919 | 0.037 | 0.523 |
TCDCA | 0.003 | 0.957 | 0.009 | 0.876 |
TDCA | 0.005 | 0.929 | −0.094 | 0.107 |
TLCA | 0.020 | 0.732 | −0.033 | 0.575 |
TUDCA | 0.021 | 0.717 | −0.082 | 0.159 |
Logistic regression model analysis of risk factors for colonic neoplasms
A univariate logistic regression analysis was conducted with the presence or absence of colonic neoplasms as the dependent variable and various other indicators as independent variables, aiming to investigate the risk factors for colonic neoplasms. Table 5 presents the findings, which indicated that CDCA (B = 0.000, OR = 1.000, P = 0.049), GCDCA (B = 0.000, OR = 1.000, P = 0.043), GDCA (B = 0.000, OR = 1.000, P = 0.043), and primary BA (B = 0.000, OR = 1.000, P = 0.020) were risk factors for colonic neoplasms formation and were connected with the risk of colonic neoplasms (P < 0.05). Multivariate logistic regression analysis was performed using indicators with statistically significant differences in univariate analysis. The findings indicated that GDCA (B = −0.001, OR = 0.999) was a protective factor for the development of colonic neoplasms.
Table 5Risk factors for colonic neoplasms: Univariate and multivariate logistic regression analysis
Variable | Univariate analysis
| Multivariate analysis
|
---|
OR (95%CI) | P value | OR (95%CI) | P value |
---|
CA | 1.000 (1.000, 1.001) | 0.158 | | |
CDCA | 1.000 (1.000, 1.000) | 0.049 | 1.000 (0.999, 1.001) | 0.878 |
DCA | 1.000 (1.000, 1.000) | 0.643 | | |
LCA | 1.000 (0.999, 1.001) | 0.655 | | |
UDCA | 1.000 (1.000, 1.001) | 0.363 | | |
GCA | 1.000 (1.000, 1.001) | 0.397 | | |
GCDCA | 1.000 (1.000, 1.000) | 0.043 | 1.000 (1.000, 1.001) | 0.406 |
GDCA | 1.000 (0.999, 1.000) | 0.043 | 0.999 (0.998, 1.000) | 0.001 |
GLCA | 0.999 (0.998, 1.000) | 0.193 | | |
GUDCA | 1.000 (1.000, 1.001) | 0.311 | | |
TCA | 1.000 (0.998, 1.002) | 0.771 | | |
TCDCA | 1.001 (0.999, 1.002) | 0.270 | | |
TDCA | 0.998 (0.995, 1.001) | 0.135 | | |
TLCA | 0.997 (0.987, 1.007) | 0.556 | | |
TUDCA | 1.005 (0.993, 1.017) | 0.396 | | |
primary BA | 1.000 (1.000, 1.000) | 0.020 | 1.000 (1.000, 1.001) | 0.720 |
primary free BA | 1.000 (1.000, 1.000) | 0.051 | | |
primary conjugated BA | 1.000 (1.000, 1.000) | 0.092 | | |
secondary BA | 1.000 (1.000, 1.000) | 0.429 | | |
secondary free BA | 1.000 (1.000, 1.000) | 0.857 | | |
secondary conjugated BA | 1.000 (1.000, 1.000) | 0.153 | | |
Discussion
The occurrence and development of colonic neoplasms result from long-term evolution through comprehensive interactions between changes in genetic material and the external environment. Recent studies suggest that high concentrations of BAs may be known to induce cancer.8 By triggering different signaling pathways in the body, BAs, as signaling molecules, can alter the colonic environment and regulate the development of colonic neoplasms.9
This study discovered that the colonic neoplasms group had a much higher amount of primary conjugated BAs (GCDCA, TCA, and TCDCA) than the control group (P < 0.05). A nested case-control analysis on 581 cases of primary colonic cancer identified between 1993 and 2008 was carried out in prior research by K ü hn T et al., who discovered a positive correlation between cancer risk and plasma levels of seven conjugated BA metabolites.10 There are two secondary conjugated BAs, GDCA and TDCA, and five primary conjugated BAs, GCA, TCA, GCDCA, TCDCA, and GHCA. Consistent with the prior research, this study’s findings suggest that elevated levels of primary conjugated BAs may be associated with an increased risk of colonic cancer. Experts and academics now widely agree that DCA plays a role in the onset and progression of colonic neoplasms. Numerous investigations have demonstrated a connection between colonic neoplasms and elevated fecal DCA levels.11,12 It is yet unknown whether variations in serum DCA levels and the emergence of colonic neoplasms are related.
Moreover, it is still unclear if the patterns of DCA alterations in a person’s serum and feces are the same. The study findings presented in this article suggest that patients with colonic neoplasms have lower serum levels of secondary free BA DCA. There is still no agreement regarding the pattern of alterations in other BA components in patients with colonic neoplasms.13 The results of various research’ detection and analysis varies significantly.6 It is evident, therefore, that the serum BA profiles of patients with colonic neoplasms differ from those of normal individuals. These differences are somewhat associated with the onset and progression of colonic neoplasms. We should incorporate the patients’ blood and fecal BA profiles in follow-up investigations and perform synchronous comparison analysis to better understand the role of BA profiles in colonic neoplasms.
After further categorizing and assessing the colonic neoplasms group based on pathological type, we discovered statistical variations in CA, UDCA, and GUDCA amongst neoplasms with various pathological types. In this study, the non-adenomatous polyp group had higher levels of UDCA and GUDCA than the adenomatous polyp group, which was followed by the colonic cancer group. We hypothesize that UDCA and GUDCA could offer novel targets and approaches for the prophylaxis and management of colonic neoplasms. A correlation analysis was performed between the levels of serum BA profile and the pathological parameters of colonic neoplasms. The results indicated that there was a negative link between the pathological types of the neoplasms and CDCA and GUDCA. We can draw the conclusion that the incidence and progression of colonic neoplasms are associated with the decline in CDCA and GUDCA levels. GDCA (B = −0.001, OR = 0.999) was identified as a protective factor for the development of colonic neoplasms through logistic regression analysis of the risk factors, but the correlation between GDCA and colonic neoplasms was not strong. The aforementioned results suggest that in clinical practice, we should actively advise patients with alterations in BA composition—particularly when UDCA, GUDCA, and CDCA levels fall—to enhance colonoscopy examination. Such improvements will enhance patient prognosis and alleviate the burden on survivors.
Previous studies have analyzed the role and mechanism of BA profiles in the occurrence and development of colonic neoplasms. The widely recognized view is that increasing the concentration of DCA in the BA profiles can promote the occurrence of colonic neoplasms, while increasing the concentration of UDCA may inhibit the occurrence and development of tumors.14,15 Besides, research has found that through numerous mechanisms, including the induction of β-catenin signal transduction, the upregulation of Cyclin D1 expression, the degradation of p53, and the promotion of resistance to cell death, DCA can induce aberrant proliferation and malignant transformation of colon cells.16,17 Giving DCA-rich meals to Apcmin/+ mice led to an increase in the size and quantity of adenomas in their intestines, as well as an increase in the adenoma adenocarcinoma sequence, according to research by Liu et al.18 In the intestinal mucosal tissue of DCA-treated mice, cytoplasmic tight adhesin-1, intestinal cell count, and the amount of released immunoglobulin A were all shown to be significantly lower. The findings suggest that by controlling the intestinal barrier, DCA may facilitate the growth of intestinal neoplasms. Colonic cancer is thought to be prevented by UDCA.19 Studies have revealed that UDCA possesses anti-inflammatory, anti-apoptotic, and antioxidant properties in mice’s digestive systems.20 In the AOM model of experimental mouse colonic cancer, Sharad Khare et al.21 discovered that DCA significantly increases tumorigenesis, but UDCA can reduce AOM carcinogenesis by preventing DCA-induced p38 activation and lowering the overexpression of C/EBPβ and Cox-2. Furthermore, UDCA can prevent DCA-induced transcription factor activation of AP-1 and NF-κB.22 Interventions targeting NF-κB and AP-1 may partially slow the growth of colonic cancer. This investigation has found that the content of UDCA changes in patients with different pathological types of colonic neoplasms. Further research is required to fully understand UDCA’s utility in detecting and managing colonic cancer patients.
In conclusion, there is a significant correlation between the incidence and progression of colonic cancers and the level of BA profiles. The potential therapeutic targeting of different BA profile components for colonic cancers remains a subject of ongoing debate, necessitating more research. This work indicates that regulating the content and composition of serum BA, even in the stage of colonic polyps and in the absence of intestinal abnormalities, can somewhat inhibit polyp formation and prevent its progression into cancer. Furthermore, this study acknowledges certain limitations. Firstly, this study is retrospective, and various confounding factors, such as the inconsistency in the operator performing the colonoscopies among the study subjects, current gastrointestinal symptoms, past disease history, and other elements, may have impacted the research outcomes. Secondly, the scope of the research findings was limited, with the analysis confined to serum BA profiles. Future research could extend to obtaining both fecal and serum samples from participants, allowing for comparison and analysis of the BA profile compositions of the two to identify more distinctive biomarkers. For future experimental designs, improvements are necessary, including expanding the sample size, collecting fecal samples, and conducting multicenter studies in collaboration with other hospitals. These steps will provide evidence for identifying effective targets to reduce the production of colonic polyps and decrease the incidence of colonic cancer.