Correlation Analysis Between Serum Bile Acid Profiles and Colonic Neoplasms

doi:10.14218/CSP.2024.00002

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Correlation Analysis Between Serum Bile Acid Profiles and Colonic Neoplasms

Xin Ji¹ and
Hong Chen^1,2,*

Cancer Screening and Prevention 2024;3(1):1-7

doi: 10.14218/CSP.2024.00002

Received: January 16, 2024

Revised: February 27, 2024

Accepted: March 22, 2024

Published online: March 25, 2024

Author information

Citation: Ji X, Chen H. Correlation Analysis Between Serum Bile Acid Profiles and Colonic Neoplasms. Cancer Screen Prev. 2024;3(1):1-7. doi: 10.14218/CSP.2024.00002.

Abstract

Background and objectives

Currently, the mechanism of occurrence and development of colonic polyps and colonic cancer has not been fully elucidated. Previous studies have shown a certain relationship between bile acid (BA) profile and the development of colonic cancer. Through an analysis of the relationship between alterations in the serum BA profile and colonic neoplasms, this study sought to explore potential associations relevant to future biomarker and therapeutic-target research.

Methods

This retrospective study encompassed 135 individuals who showed no abnormalities during colonoscopy, 204 patients with colonic polyps, and 92 patients with colonic cancer, all diagnosed and treated at Zhongda Hospital, Southeast University, from January 1, 2022, to June 1, 2023. Serum BA profiles, liver function, and clinical data were collected for statistical analysis.

Results

The concentration of deoxycholic acid in patients with colonic neoplasms was lower than that in the control group, whereas levels of taurocholic acid, taurochenodeoxycholic acid, and glycochenodeoxycholic acid were significantly higher in the colonic neoplasms group than in the control group (P < 0.05). Subgroup analyses suggested differences in cholic acid and ursodeoxycholic acid among pathological types, with a borderline reported result for glycoursodeoxycholic acid (P = 0.050). In the reported multivariable logistic regression model, glycodeoxycholic acid had an odds ratio below 1 (P = 0.001); interpretation requires confirmation of outcome coding and model specification.

Conclusions

The reported serum BA profiles differed between the neoplasms and control groups. The reported neoplasms group had higher levels of selected primary conjugated BAs and lower deoxycholic acid levels. These exploratory findings require confirmation.

Keywords

Serum, Bile acid profile, Colonic neoplasms, Colonic polyps, Colonic cancer, Bile acid metabolism, Deoxycholic acid, DCA, Primary conjugated BAs

Introduction

In 2020, colorectal cancer was the second leading cause of cancer death and the third most commonly diagnosed cancer worldwide.¹ Colonic polyps are detected by colonoscopy, and adenomatous polyps are important precursors of colonic cancer.² Histopathological examination helps distinguish polyp subtypes and identify dysplasia or malignant changes.³ The adenoma–carcinoma sequence represents one pathway of colorectal carcinogenesis. Clinicians are increasingly focusing on the detection and management of adenomatous polyps in colorectal cancer screening.^4,5 Early detection and management of colonic polyps can markedly decrease the incidence of colonic cancer. Currently, the underlying mechanisms of colonic polyps and cancer development are not fully elucidated. Over the past decade, research has highlighted bile acids (BAs) as critical signaling molecules in the genesis of colonic neoplasms.⁶ Experimental evidence links microbial BA metabolism to colonic tumorigenesis, although the relationship between serum BA profiles and colonic neoplasms remains incompletely understood.⁷ This study compared the levels of 15 serum BAs between colonic neoplasm patients and control participants and preliminarily explored the changes in serum BA profiles of colonic neoplasm patients. It analyzed the relationship between BA profiles and the presence of colonic neoplasms, to inform future research on potential biomarkers and therapeutic targets.

Materials and methods

Study participants

The study conducted a retrospective analysis of 204 patients with colonic polyps and 92 patients with colonic cancer who received treatment at the Zhongda Hospital Southeast University between January 1, 2022, and June 1, 2023. They were identified from the electronic medical record system and included in the colonic neoplasms group. The patients had an average age of (56.82 ± 8.74) years, with 160 males and 136 females. Inclusion criteria: (a) Participants aged 30–75 years who had undergone colonoscopy and received a pathological diagnosis of polyps or adenocarcinoma; (b) Serum BA profiles and liver function testing were completed one week before colonoscopy. Exclusion criteria: (a) Previous history of inflammatory bowel disease; (b) Previous liver and biliary system diseases, such as autoimmune hepatitis, sclerosing cholangitis, viral liver disease, cirrhosis, etc; (c) Previous intestinal surgery (excluding appendectomy); (d) Severe cardiopulmonary and renal dysfunction; (e) Patients with other malignant tumors; (f) Patients who had received chemotherapy or immunotherapy; (g) Pregnant women. The control group comprised 135 participants who underwent colonoscopy at the same facility during the same period and had no appreciable abnormalities on examination. They had an average age of (55.35 ± 8.79) years, with 61 men and 74 women. The exclusion criteria were the same as those for the colonic neoplasms group. This study was reviewed and approved by the Zhongda Hospital Institutional Review Board (Approval No. 2021ZDSYLL297-P01). All procedures were carried out in accordance with the Declaration of Helsinki (as revised in 2013). The requirement for individual consent for this retrospective analysis was waived.

Research methods

Clinical information on study participants, including age, gender, body mass index (BMI), liver function, serum BA profiles, and tumor pathological parameters specific to the colonic neoplasms group, was collected. Liver function and BA profiles were assessed in all serum samples obtained during fasting.

Determination of serum BA profile

High-performance liquid chromatography-tandem mass spectrometry was used to identify 15 different forms of BAs in the BA profile, including (a) primary free BAs: cholic acid (CA) and chenodeoxycholic acid (CDCA), (b) primary conjugated BAs: taurocholic acid (TCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), and glycochenodeoxycholic acid (GCDCA), (c) secondary free BAs: deoxycholic acid (DCA), ursodeoxycholic acid (UDCA), and lithocholic acid (LCA); (d) secondary conjugated BAs: taurodeoxycholic acid (TDCA), glycodeoxycholic acid (GDCA), tauroursodeoxycholic acid (TUDCA), glycoursodeoxycholic acid (GUDCA), taurolithocholic acid (TLCA), and glycolithocholic acid (GLCA).

Sample processing for BA detection

Sample aliquots of 100 µL were mixed sequentially with 25 µL of deuterated BA internal standard solution and 200 µL of an acetonitrile–methanol mixture, centrifuged at 4°C for 10 minutes at 14,000 r/min, and 150 µL of supernatant was collected for testing.

Liquid chromatography conditions

The chromatography column employed an Eclipse Plus C18 analytical column (100 × 3.0 mm, 3.5 µm). Mobile phase A consisted of a formic acid aqueous solution (pH = 3.25), and mobile phase B was a solution containing acetonitrile (acetonitrile: methanol = 80:20). The injection volume ranged from 1–10 µL (adjusted according to the analysis and instrument sensitivity). The column temperature was set at 40°C, utilizing gradient elution.

Mass spectrometry parameters

An electrospray ion source was used in negative-ion mode with multiple reaction monitoring. The ion source temperature was 550°C, and the ionization voltage was −4,500 V.

Statistical analysis

SPSS 26.0 was used for statistical analysis. Continuous data were assessed for normality and homogeneity of variance. Normally distributed continuous data were expressed as mean ± standard deviation, and an independent-samples t-test was used to compare two groups. Skewed continuous data were expressed as the median (25th, 75th percentiles) [M (P25, P75)]. When comparing two groups, the Mann-Whitney U test was used; the Kruskal-Wallis H test was used for comparisons among several groups. The chi-square test was used to compare categorical data between groups. Spearman rank correlation was used for correlation analysis. The association between BA profiles and the presence of colonic neoplasms was analyzed using binary logistic regression. P < 0.05 indicated that the difference was statistically significant. The specific post-hoc comparison method and any adjustment for multiple comparisons were not specified in the available report; these analyses are interpreted as exploratory.

Results

Comparison of participant characteristics

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 (Table 1).

Table 1

Comparison 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

Reference value range: ALT 9–50 U/L; AST 15–40 U/L; TC 0.00–6.20 mmol/L. ALT, alanine transaminase; AST, aspartate transaminase; BMI, body mass index; TC, total cholesterol.

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 2

Detection 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

Values are median (25th, 75th percentiles). *P < 0.05 for the between-group comparison. The neoplasms sample size is reported as 204 in this table and 296 in the participant description; the analysis population could not be verified. BA, bile acid; CA, cholic acid; CDCA, chenodeoxycholic acid; DCA, deoxycholic acid; GCA, glycocholic acid; GCDCA, glycochenodeoxycholic acid; GDCA, glycodeoxycholic acid; GLCA, glycolithocholic acid; GUDCA, glycoursodeoxycholic acid; LCA, lithocholic acid; TCA, taurocholic acid; TCDCA, taurochenodeoxycholic acid; TDCA, taurodeoxycholic acid; TLCA, taurolithocholic acid; TUDCA, tauroursodeoxycholic acid; UDCA, ursodeoxycholic acid.

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, overall comparisons suggested differences in CA (P = 0.011) and UDCA (P = 0.009), with a borderline reported result for GUDCA (P = 0.050). The other BA components had P values > 0.05. 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 from reported pairwise comparisons and should be interpreted as exploratory because the post-hoc procedure and multiplicity adjustment were not specified.

Table 3

Comparison 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*

Values are median (25th, 75th percentiles). H, Kruskal-Wallis test statistic. *P < 0.05 for the overall comparison among the three groups. Displayed P values are rounded, and the original significance indicators are retained; the unrounded GUDCA P value could not be verified. BA, bile acid; CA, cholic acid; CDCA, chenodeoxycholic acid; DCA, deoxycholic acid; GCA, glycocholic acid; GCDCA, glycochenodeoxycholic acid; GDCA, glycodeoxycholic acid; GLCA, glycolithocholic acid; GUDCA, glycoursodeoxycholic acid; LCA, lithocholic acid; TCA, taurocholic acid; TCDCA, taurochenodeoxycholic acid; TDCA, taurodeoxycholic acid; TLCA, taurolithocholic acid; TUDCA, tauroursodeoxycholic acid; UDCA, ursodeoxycholic acid.

Correlation analysis between serum BA profile levels and clinical pathological parameters of colonic neoplasms

The reported P values for Spearman correlations between serum BA components and tumor size were all > 0.05 (Table 4). The GCA–tumor size coefficient requires verification and is not interpreted. Negative correlations with the coded pathological categories were reported for CDCA (r = −0.121, P = 0.038) and GUDCA (r = −0.149, P = 0.010). The direction of these correlations cannot be interpreted clinically without the category coding.

Table 4

Correlation analysis between serum BA profile levels and clinicopathological parameters of colonic neoplasms

BA components	Size of tumor		Pathological type
BA components	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

Spearman correlations are reported. The GCA–tumor size entry (r = −1.000, P = 0.085) remains unverified and is not interpreted. Analysis sample sizes, the definition and unit of tumor size, and pathological-category coding were not specified. BA, bile acid; CA, cholic acid; CDCA, chenodeoxycholic acid; DCA, deoxycholic acid; GCA, glycocholic acid; GCDCA, glycochenodeoxycholic acid; GDCA, glycodeoxycholic acid; GLCA, glycolithocholic acid; GUDCA, glycoursodeoxycholic acid; LCA, lithocholic acid; TCA, taurocholic acid; TCDCA, taurochenodeoxycholic acid; TDCA, taurodeoxycholic acid; TLCA, taurolithocholic acid; TUDCA, tauroursodeoxycholic acid; UDCA, ursodeoxycholic acid.

Logistic regression analysis of BA measures and colonic neoplasms

A univariable logistic regression analysis was conducted with the presence or absence of colonic neoplasms as the dependent variable and various other indicators as independent variables, to explore associations with 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) had reported P values < 0.05 in univariable analyses. Multivariable logistic regression analysis was performed using indicators with statistically significant differences in univariable analysis. GDCA (B = −0.001, OR = 0.999, 95% CI: 0.998–1.000, P = 0.001) had an OR below 1 in the reported multivariable model. Interpretation requires confirmation of outcome coding and model specification.

Table 5

BA measures and colonic neoplasms: Univariable and multivariable logistic regression analysis

Variable	Univariable analysis		Multivariable analysis
Variable	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

OR, odds ratio; CI, confidence interval. Estimates retain the reported precision. The modeled outcome category and concentration increment were not specified; the direction and magnitude of the disease association therefore require confirmation. BA, bile acid; CA, cholic acid; CDCA, chenodeoxycholic acid; DCA, deoxycholic acid; GCA, glycocholic acid; GCDCA, glycochenodeoxycholic acid; GDCA, glycodeoxycholic acid; GLCA, glycolithocholic acid; GUDCA, glycoursodeoxycholic acid; LCA, lithocholic acid; TCA, taurocholic acid; TCDCA, taurochenodeoxycholic acid; TDCA, taurodeoxycholic acid; TLCA, taurolithocholic acid; TUDCA, tauroursodeoxycholic acid; UDCA, ursodeoxycholic acid.

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 have identified alterations in BA receptor signaling in human colon 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 higher levels of selected 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 Kühn et al., who discovered a positive correlation between cancer risk and plasma levels of seven conjugated BA metabolites.¹⁰ These included two secondary conjugated BAs, GDCA and TDCA, and five primary conjugated BAs, GCA, TCA, GCDCA, TCDCA, and glycohyocholic acid (GHCA). The present findings also suggest an association involving selected primary conjugated BAs, although this retrospective comparison does not establish future cancer risk. DCA has been implicated 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. Observational studies have also reported inconsistent associations between individual fecal BA components and colorectal neoplasia.¹³ Findings for circulating BAs vary across studies.⁶ The present results suggest differences in selected serum BA components between the reported neoplasms and control groups. These differences do not establish whether BA alterations precede or follow 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 observed variation in CA and UDCA, with a borderline overall result for GUDCA. In this study, the non-adenomatous polyp group had higher median levels of UDCA and GUDCA than the adenomatous polyp group, which was followed by the colonic cancer group. These descriptive patterns support further investigation of UDCA and GUDCA in colonic neoplasms. A correlation analysis was performed between the levels of serum BA profile and the pathological parameters of colonic neoplasms. The reported results showed negative correlations of CDCA and GUDCA with coded pathological categories, although the coding was not specified. Differences between pathological categories do not establish a temporal relationship with disease progression. GDCA (B = −0.001, OR = 0.999) had an OR below 1 in the reported logistic regression model; this does not establish a protective effect, and proximity of the rounded OR to 1 does not by itself indicate a weak association. Whether BA measures could aid colonoscopy referral requires dedicated diagnostic validation. Effects on prognosis and survival were not evaluated in this study.

Previous studies have analyzed the role and mechanism of BA profiles in the occurrence and development of colonic neoplasms. Experimental studies suggest that DCA can promote tumorigenesis, whereas UDCA may have antitumor effects in some models.^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 DCA administration to Apc^min/+ mice led to an increase in the size and quantity of adenomas in their intestines, as well as promotion of the adenoma–adenocarcinoma sequence, according to research by Liu et al.¹⁸ In the intestinal mucosal tissue of DCA-treated mice, the tight junction protein zonula occludens 1 (ZO-1), goblet and Paneth cell numbers, and secretory immunoglobulin A levels were all shown to be significantly lower. The findings suggest that by disrupting the intestinal barrier, DCA may facilitate the growth of intestinal neoplasms. UDCA has also been investigated in relation to the gut microbiome and colorectal adenoma development.¹⁹ In cholestatic pregnancy, UDCA treatment has been associated with changes in intestinal microbial composition and BA metabolism.²⁰ In experimental models of colonic cancer, Khare et al.²¹ reported suppression of Cox-2 expression by UDCA, implicating Ras, p38, and CCAAT/enhancer-binding protein signaling. Furthermore, UDCA can prevent DCA-induced transcription factor activation of AP-1 and NF-κB.²² These mechanistic findings require clinical validation before therapeutic conclusions can be drawn. 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.

Overall, this study reports differences in selected serum BA components between the groups studied. The potential therapeutic targeting of different BA profile components for colonic cancers remains a subject of ongoing debate, necessitating more research. These findings support further investigation of serum BA profiles but do not establish that modifying BA composition prevents polyp formation or progression to 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 could help assess the potential diagnostic and therapeutic relevance of BA profiles in colonic neoplasms.

Several reporting limitations further constrain interpretation. The available report does not specify whether participants were consecutively included, exclusions for incomplete records or samples, missing-data handling, or the rationale for the sample size. The specimen matrix is described inconsistently as serum and plasma, and the actual matrix remains unverified. Instrument identification, the exact injection volume, gradient program, calibration and assay validation, and quality-control details are incompletely reported; TDCA and TUDCA measurement labels could not be checked against assay standards or original outputs. Analysis denominators and pathological-category coding remain uncertain, as noted in the table footnotes. The logistic regression report does not specify outcome coding, composite-variable formulas, adjustment for age, sex, BMI or other confounders, or assessment of multicollinearity and linearity in the logit. Overlap between individual BAs and composite measures may affect model stability. These limitations preclude firm clinical interpretation of the regression estimates and require the findings to be regarded as exploratory.

Conclusions

This study suggests a potential relationship between serum BA levels and the presence of colonic neoplasms. The reported neoplasms group had higher levels of selected primary conjugated BAs (TCA, TCDCA, and GCDCA) and lower DCA levels. Further research is necessary, as the current understanding of how components of the BA profile are involved in colonic neoplasms remains unclear. The findings are exploratory and do not establish causality, diagnostic performance, or a basis for clinical intervention.

Abbreviations

ALT:: alanine transaminase

AST:: aspartate transaminase

BA:: bile acid

BMI:: body mass index

CA:: cholic acid

CDCA:: chenodeoxycholic acid

DCA:: deoxycholic acid

GCA:: glycocholic acid

GCDCA:: glycochenodeoxycholic acid

GDCA:: glycodeoxycholic acid

GLCA:: glycolithocholic acid

GUDCA:: glycoursodeoxycholic acid

LCA:: lithocholic acid

TC:: total cholesterol

TCA:: taurocholic acid

TCDCA:: taurochenodeoxycholic acid

TDCA:: taurodeoxycholic acid

TLCA:: taurolithocholic acid

TUDCA:: tauroursodeoxycholic acid

UDCA:: ursodeoxycholic acid

Declarations

Acknowledgement

We want to thank all the patients for actively cooperating in this study.

Ethical statement

This study was reviewed and approved by the Zhongda Hospital Institutional Review Board (Approval No.2021ZDSYLL297-P01). All procedures were carried out in accordance with the ethical guidelines of the Helsinki Declaration (as revised in 2013). The individual consent for this retrospective analysis was waived.

Data sharing statement

Data supporting the research article are available from the corresponding author or first author upon reasonable request.

Funding

This project receives no financial support.

Conflict of interest

There are no conflict of interests regarding the publication of this paper.

Authors’ contributions

Contributed to study concept and design (XJ and HC), performance of experiments (XJ), analysis and interpretation of data (XJ and HC), manuscript writing (XJ), critical revision (XJ and HC), statistical analysis (XJ), technical or material support (HC).

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Ji X, Chen H. Correlation Analysis Between Serum Bile Acid Profiles and Colonic Neoplasms. Cancer Screen Prev. 2024;3(1):1-7. doi: 10.14218/CSP.2024.00002.

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Article History

Received	Revised	Accepted	Published
January 16, 2024	February 27, 2024	March 22, 2024	March 25, 2024

DOI http://dx.doi.org/10.14218/CSP.2024.00002

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