Efficacy of endoscopic nasobiliary drainage for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis and cholangitis after repeated clearance of common bile duct stones: experience from a Chinese center.

BACKGROUND: The aim of the present study was to investigate whether it is reasonable to insert an endoscopic nasobiliary drainage (ENBD) tube in patients with endoscopic sphincterotomy (EST) and repeated clearance of common bile duct (CBD) stones. PATIENTS AND METHODS: Patients with choledocholithiasis who underwent EST and CBD stone clearance at our center from January 2010 to May 2012 were reviewed. The following parameters were evaluated: (i) serum amylase 2 and 24 h after ERCP; (ii) incidence of endoscopic retrograde cholangiopancreatography (ERCP)-related pancreatitis and cholangitis; (iii) time elapsed to normalization of total serum bilirubin levels for those with jaundice before ERCP; and (iv) length of hospital stay. RESULTS: Compared with the no-ENBD group, the ENBD group presented a significantly lower postoperative serum amylase of 2 and 24 h (81.3 ± 31.8 U/L vs 90.8 ± 31.2 U/L, 107.0 ± 51.1 U/Lvs 132.3 ± 100.8 U/L, respectively). The incidence of post-ERCP pancreatitis and cholangitis was also lower in the ENBD group, although the differences were not significant (1% vs 4.4%, 0 vs 4.5%, respectively). Time elapsed to normalization of total serum bilirubin levels and length of hospital stay was shorter in the ENBD group (4.3 days ± 0.6 days vs 4.5 days ± 0.7 days, P > 0.05; 4.8 days ± 2.1 days vs 6.3 days ± 2.8 days, respectively, P < 0.01). CONCLUSIONS: ENBD significantly reduces the incidence of hyperamylasemia and decreases the length of hospital stay in patients with EST and repeated stone extraction. ENBD should be considered for patients with large or multiple CBD stones.

A genetic variant in microRNA-196a2 is associated with increased cancer risk: a meta-analysis.

MicroRNAs (miRNAs) are small non-coding RNA molecules that function as negative regulators of gene expression. Common genetic variants (single nucleotide polymorphisms, SNPs) in miRNA genes may alter their expression or maturation resulting in varied functional consequences. Until now, several studies had evaluated the association between the polymorphisms in the hsa-miR-196a2 rs11614913 and cancer risk in diverse populations and in multiple types of cancer, with contradictory outcomes. Therefore, here we performed a meta-analysis to address the association between this polymorphism and cancer risk. A total of nine studies involving 6,540 cases and 7,562 controls were retrieved based on PubMed. Our analysis demonstrated that hsa-miR-196a2 rs11614913 CC genotype significantly increased the cancer risk in homozygote comparison model compared to TT genotype (OR=1.18; 95% CI, 1.01-1.68). Moreover, significant association of this polymorphism with breast cancer was found based on homozygote comparison model (OR=1.30; 95% CI, 1.01-1.26) and dominant model (OR=1.11; 95% CI, 1.01-1.23). In addition, hsa-miR-196a2 rs11614913 CC genotype was significantly associated with cancer risk in Chinese and Indian (OR=1.21; 95% CI, 1.05-1.40), but not in Caucasians (OR=1.03; 95% CI, 0.89-1.19). Taken together, our results indicate that the polymorphism of hsa-miR-196a2 rs11614913 is associated with cancer susceptibility, especially with breast cancer and in Chinese and Indian populations.

Delayed surgery for rectal cancer patients receiving neoadjuvant chemoradiotherapy: a promising method in its infancy.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) is used to downstage locally advanced rectal cancer before surgery. Accumulating data suggest that tumor response to nCRT is time dependent. A delay between nCRT and surgery may increase the proportion of patients that achieve a favorable response. However, delayed surgery beyond 6-8 weeks may increase the technical difficulty, and the risks of surgical complications and recurrence or metastasis. This article briefly reviews the relevant literature to evaluate the efficiency and safety of delayed surgery. METHODS: Two non-cohort studies and 10 cohort studies were reviewed. The results were analyzed and the limitations discussed. RESULTS: Although debatable, the findings of the included studies are promising. Delayed surgery may increase the proportion of favorable tumor response without compromising prognosis. However, most of the studies were retrospective, which introduces bias into the evaluation. CONCLUSION: Delayed surgery is potentially useful, but this needs to be verified by further well-designed prospective trials.

Endoscopic biliary stenting for irretrievable common bile duct stones: Indications, advantages, disadvantages, and follow-up results.

BACKGROUND: The advantages of endoscopic retrograde cholangiopancreatography (ERCP) over open surgery have made it the predominant method of treating patients with choledocholithiasis. After sphincterotomy, however, 10%-15% of common bile duct (CBD) stones cannot be removed with a basket or balloon. Methods for managing "irretrievable stones" include surgery; mechanical, intraductal shock wave, and extracorporeal shock wave lithotripsy; chemical dissolution; and biliary stenting. Endoscopic biliary stent insertion, which is frequently used in specific situations, has both advantages and disadvantages. To maximize the advantages and minimize the complications of biliary endoprosthesis, it is important to recognize its proper indications and to apply the technique in proper situations. DATA SOURCES: We reviewed all publications cited in Pubmed and published through July 2011 on biliary endoprosthesis in patients with irretrievable CBD stones. We analyzed the indications, advantages, disadvantages, and long-term follow-up results of this technique. RESULTS: Despite the occurrence of related complications, such as cholangitis, endoscopic placement of an endoprosthesis may reduce stone size, allowing later clearance of unextractable stones. Permanent biliary stenting may be a definitive treatment in selected elderly patients who are poor candidates for surgery. CONCLUSION: Endoscopic biliary stenting remains a simple and safe method for patients with stones difficult to manage by conventional endoscopic methods and those patients unfit for surgery or at high surgical risks.

Human embryonic stem cells and metastatic colorectal cancer cells shared the common endogenous human microRNA-26b.

The increase in proliferation and the lack of differentiation of cancer cells resemble what occur in the embryonic stem cells during physiological process of embryogenesis. There are also striking similarities in the behaviour between the invasive placental cells and invasive cancer cells. In the present study, microarrays were used to analyse the global expression of microRNAs in a human embryonic stem cell line (i.e. HUES-17) and four colorectal cancer (CRC) cell lines (i.e. LoVo, SW480, HT29 and Caco-2) with different metastatic potentialities. Only the expression of miR-26b was significant decreased in HUES-17s and LoVo cells, compared with other three cell lines (P < 0.01). The quantitative real-time PCR analysis confirmed the results of the microarray analysis. Overexpression of miR-26b expression by miR-26 mimics transfection and led to the significant suppression of the cell growth and the induction of apoptosis in LoVo cells in vitro, and the inhibition of tumour growth in vivo. Moreover, the potential targets of miR-26b was predicted by using bioinformatics, and then the predicted target genes were further validated by comparing gene expression profiles between LoVo and NCM460 cell lines. Four genes (TAF12, PTP4A1, CHFR and ALS2CR2) with intersection were found to be the targets of miR-26b. MetaCore network analysis further showed that the regulatory pathways of miR-26b were significantly associated with the invasiveness and metastasis of CRC cells. These data suggest that miR-26b might serve as a novel prognostic factor and a potential therapeutic target for CRC.

Synchronous colorectal cancers: a review of clinical features, diagnosis, treatment, and prognosis.

BACKGROUND/AIMS: With the development of early diagnostic technologies, more synchronous colorectal cancers (SCRCs) can be clinically detected. Although SCRCs are recognized as a significant clinical entity, their clinical features, diagnosis, treatment, and prognosis have yet to be definitively established. In order to obtain a comprehensive understanding of this disease and to establish an efficient profile by which to recognize individuals at high risk of developing SCRCs, we carried out a review of the relevant literature. METHODS: The PubMed database was searched for publications of 'synchronous colorectal carcinoma/cancer/adenocarcinoma' and 'multiple colorectal carcinomas'. All publications up to January 2011 were considered, and then only articles in English were retrieved for inclusion in this review. RESULTS: The incidence of SCRCs was found to be higher in older and male patients. The prognosis in patients with SCRCs was equivalent to that in patients with solitary CRC. The failure to diagnose synchronous lesions before and during the operation was associated with repeated surgery. CONCLUSION: SCRCs possess distinctive features compared to solitary CRC. While all colorectal patients should be carefully assessed to rule out the presence of concurrent colon adenomas, since missed lesions can result in additional surgery and poor prognosis, particular attention should be given to the high-risk group of older male patients.

Waldeyer's fascia: anatomical location and relationship to neighboring fasciae in retrorectal space.

PURPOSE: The term Waldeyer's fascia has caused confusion in surgery for rectal cancer. We have therefore dissected endopelvic fasciae to clarify the structure and location of Waldeyer's fascia, and to determine its anatomical relationships with adjacent fasciae. METHODS: Twenty cadavers (13 males and 7 females) were dissected. Each specimen was sectioned in the sagittal plane and both hemipelvises were examined. RESULTS: Waldeyer's fascia was observed in all specimens originating from the presacral fascia at the S2-S4 level and fusing with the posterior leaf of the mesorectal parietal fascia. Waldeyer's fascia divided the retrorectal space (RRS) into inferior and superior compartments, with the upper leaf constituting the floor of the superior compartment and the lower leaf constituting the dome of the inferior compartment. There were no nerves, blood vessels or lymphatic vessels within the two leaves. CONCLUSION: Waldeyer's fascia was located between the mesorectal parietal and presacral fasciae. Waldeyer's fascia included two leaves, which jointly divided the RRS into inferior and superior compartments. Waldeyer's fascia is a pivotal anatomical structure in the surgical treatment of rectal cancer.

HnRNP K and PDI marked response to chemotherapy to human colorectal cancer cells.

UNLABELLED: 5-Fluorouracil has been the chemotherapy agent of first-choice for colorectal cancer for many years, but since there are no proven predictors of a patient's response to therapy, all patients receive similar treatment. Consequently, identification of biomarkers for therapeutic effect is crucial for the development of novel therapeutic strategies. Two human colorectal cancer cell lines of different metastatic potential (LoVo and SW480) were studied. IC50 of 5-FU for both cell lines were measured by 3-(4,5-dimethy-lthiazol-2-yl)-2,5-diphenyltetrazolium assay and validated by cell cycle analysis. Then the cell lines were treated with 5-FU at IC50 concentration and protein was extracted for 2-DE. Differential protein spots were examined by MALDI-TOF/TOF MS. The expression levels of the different proteins were further confirmed by Western blot and immunofluorescence analyses. Eleven proteins were identified. Expression of heterogeneous nuclear ribonucleoprotein K (hnRNP K) in LoVo cells was higher than in SW480 cells, while protein disulfide isomerase (PDI) displayed the opposite trend. After treatment with 5-FU, the expression of hnRNP K in LoVo decreased more significantly than in SW480, while PDI in SW480 increased more significantly than in LoVo cells. CONCLUSION: hnRNP K and PDI in the two cell lines have different expression characteristics. The sensitivity to 5-FU is not consistent in tumor progression. It may assist in development of novel treatment strategies for colorectal cancer metastasis.

Heterogeneous nuclear ribonucleoprotein A1 is identified as a potential biomarker for colorectal cancer based on differential proteomics technology.

Colorectal cancer (CRC) is the third most common cancer worldwide and has poor prognosis. To identify the proteins involved in colorectal carcinogenesis, we employed 2-DE and MALDI-TOF/TOF-based proteomics approach to study the differentially expressed proteins in tumor and adjacent nontumor tissue samples. Samples from 10 colorectal patients were analyzed. Of the 7 significantly and consistently altered proteins identified, hnRNP A1 was one of the most significantly altered proteins and its overexpression was confirmed using RT-PCR and Western blot analyses. Immunohistochemical examination showed that the enhanced expression of hnRNP A1 was correlated with the increasing severity of colorectal tissue and the progression of the colorectal cancer, as well as UICC (International Union against Cancer) staging, histo-differentiation, recurrence and decreased survival. By developing a highly sensitive immunoassay, hnRNP A1 could be detected in human serum and was significantly elevated in CRC patients compared with healthy volunteers. We proposed that hnRNP A1 could be considered as a novel serum tumor marker for CRC that may have significance in the detection and in the management of patients with this disease. Knockdown of hnRNP A1 expression by RNA interference led to the significant suppression of the cell growth in colorectal cancer SW480 cells in vitro. These data suggested that hnRNP A1 may be a potential biomarker for early diagnosis, prognosis, and monitoring in the therapy of colorectal cancer. Further studies are needed to fully assess the potential clinical value of this biomarker candidate.

Ultra-high performance liquid chromatography-mass spectrometry for the metabolomic analysis of urine in colorectal cancer.

We report here the results of a pilot study in which ultra-high performance liquid chromatography/time-of- flight-mass spectrometry (UPLC/TOF-MS) and multivariate statistical analysis (supervised partial least squares discriminant analysis, PLS-DA) were applied for urinary metabolite profiling and data interpretation. The results of the PLS-DA indicated that the metabolic pattern as a whole was significantly different between the groups of preoperative colorectal cancer (CRC) patients, postoperative CRC patients, and healthy volunteers, respectively. The preoperative group of patients showed significantly increased levels of low-molecular weight compounds (LMC) MW 283 and MW 234 in comparison to the group of healthy volunteers group. After the operation, the levels of these two LMC significantly decreased. These preliminary results suggest that the UPLC-MS-based method coupled with pattern recognition will likely lead to procedures with the potential to be clinically applicable for the diagnosis of CRC and, consequently, to an improvement in patient prognosis.

Prediction of synchronous colorectal cancers by computed tomography in subjects receiving an incomplete colonoscopy: a single-center study.

AIM: To assess the value of computed tomography (CT) for diagnosis of synchronous colorectal cancers (SCRCs) involving incomplete colonoscopy. METHODS: A total of 2123 cases of colorectal cancer (CRC) were reviewed and divided into two groups according to whether a complete or incomplete colonoscopy was performed. CT results and final histological findings were compared to calculate the sensitivity and specificity associated with CT for detection of SCRCs following complete vs incomplete colonoscopy. Factors affecting the CT detection were also analyzed. RESULTS: Three hundred and seventy-four CRC patients underwent incomplete colonoscopy and 1749 received complete colonoscopy. Fifty-six cases of SCRCs were identified by CT, and 36 were missed. In the incomplete colonoscopy group, the sensitivity and specificity of CT were 44.8% and 93.6%, respectively. The positive and negative predictive values were 23.6% and 95.0%, respectively. In contrast, the sensitivity and specificity of CT for the complete colonoscopy group were 68.3% and 97.0%, while the positive and negative predictive values were 22.2% and 98.7%, respectively. In both groups, the mean maximum dimension of the concurrent cancers identified in the CT-negative cases was shorter than in the CT-positive cases (incomplete group: P = 0.02; complete group: P < 0.01) Topographical proximity to synchronous cancers was identified as a risk factor for missed diagnosis (P = 0.03). CONCLUSION: CT has limited sensitivity in detecting SCRCs in patients receiving incomplete colonoscopy. Patients with risk factors and negative CT results should be closely examined and monitored.

Screening of nutritional risk and nutritional support in general surgery patients: a survey from Shanghai, China.

To determine the prevalence of nutritional risk in surgical departments and to evaluate the impact of nutritional support on clinical outcomes. The nutritional risk in different surgical diseases and the different way of nutritional support on clinical outcomes in patients at nutritional risk remain unclear. Hospitalized patients from general surgical departments were screened using the Nutritional Risk Screening (NRS) 2002 questionnaire on admission. Data were collected on nutritional risk, complications, and length of stay (LOS). Overall, 5034 patients were recruited; the overall prevalence of nutritional risk on admission were 19.2%. The highest prevalence was found among patients with gastric cancer. At-risk patients had more complications and longer LOS than nonrisk patients. Of the at-risk patients, the complication rate was significantly lower and LOS was significantly shorter in the nutritional-support group than in the no-support group (20.9 versus 30.0%, P < 0.05). Subgroup analysis showed reduced complication rates and LOS only in patients with gastric cancer, colorectal cancer, and hepato-pancreato-biliary (HPB) cancer. Significantly lower complication rates relative to nonsupported patients were found among patients who received enteral nutrition or who received support for 5 to 7 days, or daily support entailing 16 to 25 kcal/kg of nonprotein energy. Different surgical diseases have different levels of nutritional risk. The provision of nutritional support was associated with a lower complication rate and a shorter LOS for gastric, colorectal, and HPB cancer patients at nutritional risk. The improper use of nutritional support may not improve outcomes for at-risk patients.

Prevalence, clinicopathological characteristics, treatment, and prognosis of intestinal metastasis of primary lung cancer: a comprehensive review.

AIM: Lung cancer is mostly diagnosed at the advanced stage of disease. This review focused on prevalence, clinicopathological characteristics, treatment, and prognosis of intestine metastasis of primary lung cancer. METHODS: Published literature was searched using PubMed/Medline databases to extract studies on primary lung cancer metastasized to the intestine and then analyzed statistically. RESULTS: A total of 57 case reports and 3 retrospective studies were obtained from PubMed database. The prevalence of small bowel metastasis of primary lung cancer ranged between 2.6 and 10.7%. Histologically, poor tumor differentiation and advanced T and N stages of primary lung cancer associated with intestinal metastasis. Clinically, primary lung cancer metastasized to the intestine led to three frequent clinical presentations, i.e., intestine perforation, obstruction, and bleeding. The time interval between diagnosis of primary tumor and manifestation of intestinal metastasis ranged between 2 week and 4 years, while the time was within one year for 36 reported cases. 70% (45 of 63 cases) of patients did have an extra-intestinal metastasis at diagnosis of intestine metastasis. The median survival rate of 79 patients with follow-up data was 2.3 month and the old age, extra-intestinal metastasis, and intestine perforation were associated with poor prognosis. CONCLUSION: This study suggests that the primary lung cancer metastasized to the small bowel is not so rare as it is thought. Clinical management and treatment decision will be warranted and considered accordingly.

Effect of a high-fat diet in development of colonic adenoma in an animal model.

AIM: To investigate the effect of a high-fat diet in the formation of the precursors of colorectal cancer using an animal model. METHODS: Wistar rats were divided into two groups that were fed either a high-fat diet (HFD) or a normal-fat diet (ND), and 1,2-dimethylhydrazine was administered at a dose of 40 mg/kg for 10 wk. The body weight/liver weight/epididymal fat weight were recorded after rats were sacrificed, and the formation of colonic adenoma was also observed. The levels of insulin, leptin, tumor necrosis factor (TNF)-α, insulin-like growth factor (IGF)-1 and triglycerides were determined by enzyme-linked immunosorbent assay in order to compare the altered levels of biochemical indices and inflammatory cytokines in the serum between rats fed an ND and HFD. Cell proliferation activity (Ki-67) was determined by immunohistochemical analysis. Western blot and immunofluorescence staining were used to examine the expression of proliferating cell nuclear antigen (PCNA), cyclooxygenase (COX)-2, cyclin D1, ß-catenin and nuclear factor (NF)-κB proteins in the adenoma and comparative control tissues. RESULTS: The number of colonic adenomas and the colonic epithelial Ki-67 were significantly higher in the HFD group than in the ND group. The HFD group also had increased body weight, liver weight and epididymal fat weight, which were associated with increased levels of serum insulin, leptin, TNF-α, IGF-1 and triglycerides. HFD induced upregulation of PCNA, COX-2, cyclin D1, ß-catenin and NF-κB proteins, as revealed by Western blot and immunofluorescence staining. CONCLUSION: HFD promotes the formation of colonic adenoma through inflammation, metabolic abnormalities, and increases cell cycle progression.

Knockdown of Y­box­binding protein­1 inhibits the malignant progression of HT­29 colorectal adenocarcinoma cells by reversing epithelial­mesenchymal transition.

Y­box binding protein­1 (YB­1) has been identified as an oncoprotein in various malignancies. The aim of this study was to investigate the biological role of YB­1 and its association with epithelial­to­mesenchymal transition (EMT) in colorectal cancer (CRC). The expression of YB­1 and three EMT­related proteins (E­cadherin, N­cadherin and vimentin) was analyzed in 80 CRC and matched normal tissue samples, by immunohistochemistry. The results indicated that the expression of YB­1 was higher in CRC tissue samples than that in matched normal controls and was significantly correlated with tumor differentiation, tumor invasion, lymph node metastasis and distant metastases. Furthermore, analysis showed that YB­1 expression was negatively correlated with E­cadherin and positively correlated with N­cadherin and vimentin expression. In vitro assays showed that knockdown of YB­1 inhibited the proliferation, apoptosis resistance, invasion and migration of the HT­29 CRC cell line. Of note, following knockdown of YB­1, E­cadherin expression was elevated whereas N­cadherin and vimentin expression was reduced. Taken together, these results suggest that YB­1 promotes the malignant progression of CRC in part through the induction of EMT, and YB­1 may therefore be a potential novel target for CRC treatment.

Risk factors for local recurrence following neoadjuvant chemoradiotherapy for rectal cancers.

Local recurrence (LR) has an adverse impact on rectal cancer treatment. Neoadjuvant chemoradiotherapy (nCRT) is increasingly administered to patients with progressive cancers to improve the prognosis. However, LR still remains a problem and its pattern can alter. Correspondingly, new risk factors have emerged in the context of nCRT in addition to the traditional risk factors in patients receiving non-neoadjuvant therapies. These risk factors are decisive when reviewing treatment options. This review aims to elucidate the distinctive risk factors related to LR of rectal cancers in patients receiving nCRT and to clarify their clinical significance. A search was conducted on PubMed to identify original studies investigating patients with rectal cancer receiving nCRT. Outcomes of interest, especially potential risk factors for LR in patients with nCRT, were then analyzed. The clinical importance of these risk factors is discussed. Remnant cancer cells, lymph-nodes and tumor response were found to be major risk factors. Remnant cancer cells decide the status of resection margins. Local excision following nCRT is promising in ypT0-1N0M0 cases. Dissection of lateral lymph nodes should be considered in advanced low-lying cancers. Although better tumor response resulted in a relatively lower recurrence rate, the evidence available is insufficient to justify a non-operative approach in clinical complete responders to nCRT. LR cannot be totally avoided by current multidisciplinary approaches. The related risk factors resulting from nCRT should be considered when making decisions regarding treatment selection.

Tumor stroma: a determinant role in local recurrence of rectal cancer patients receiving total mesorectal excision?

Local recurrence (LR) dramatically decreases since the adoption of total mesorectal excision (TME) but still could not be avoided. Current mainstream views try to elucidate LR by focusing on tumor cells invasion, such as tumor stage or regional lymph nodes metastasis. But we hypothesize that not tumor cells but the cancer stroma should be responsible for the LR after TME. We believed current resection range of TME may cause remnant cancer stroma, which might act as the determinant role in LR by motivating carcinogenesis of neighboring normal epithelium. A series of supportive evidences are listed and future experiments to test our hypothesis are suggested. Once this hypothesis proved, current standards of TME should be substantially rewritten concerning the resection margins.

Immunohistochemical analysis revealed CD34 and Ki67 protein expression as significant prognostic factors in colorectal cancer.

CD34, cytokeratin (CK) 19, cytokeratin (CK) 20, and Ki67 have been demonstrated to be involved in tumor invasion and angiogenesis. The aim of this study was to analyze the clinicopathological significance of CD34, CK19, CK20, and Ki67 expressions in colorectal cancer (CRC) and to evaluate their involvement in the progression of CRC. CD34, CK19, CK20, and Ki67 expressions were assessed in paraffin-embedded specimens collected from 152 cases of CRC and 30 paired normal colorectal tissues by immunohistochemistry. The relationships between CD34, CK19, CK20, and Ki67 expressions and CRC were evaluated. The association of CD34 and Ki67 protein expressions with the clinicopathological characteristics and the prognosis of CRC were subsequently assessed. CD34, CK19, CK20, and Ki67 expressed highly in CRC tissues relative to normal colorectal tissues. Using immunostaining scoring, a significant correlation of CD34 and Ki67 with the UICC staging and histo-differentiation of CRC was found (P < 0.05), but no such correlation of CK19 and CK20 with the UICC staging and histo-differentiation (P > 0.05). Meanwhile, no relationship of CD34, CK19, CK20, and Ki67 with the location of CRC was found (P > 0.05). Patients with high expressions of CD34 and Ki67 had the lowest survival (P < 0.05). The results suggest that concurrent expression of CD34 and Ki67 may be an important characteristic of CRC which may help in the prediction of CRC progression.

[Study on specific metabonomic profiling of serum from colorectal cancer patients by gas chromatography-mass spectrometry].

OBJECTIVE: To study the specific metabonomic profiling of serum from colorectal cancer patients to find out the low molecule metabolites associated intimately with colorectal cancer,and to establish specific metabolic model for the diagnosis of colorectal cancer. METHODS: The metabonomic profiles of the serum samples from colorectal cancer(CRC) patients(n =31) and healthy adults(n =8) were investigated by gas chromatography-mass spectrometry (GC-MS) technique combined with a commercial mass spectral library for the peak clustering based on metabolites. RESULTS: Thirty-four endogenous metabolites including some amino acids, carbohydrates, fatty acids and other intermediate metabolites were identified. By t test statistics with P<0.05, P<0.01 respectively, L-valine, L-threonine, 1-deoxyglucose, glycine and ribitol levels were decreased significantly, but 3-hydroxybutyric acid level was increased significantly in the CRC patient group as compared with healthy adult group. PLS-DA based on these metabolites discriminated two groups for each other. Hierarchical clustering based on above 6 significant differential metabolites revealed that the prediction accuracy of colorectal cancer group was 93.5%. CONCLUSION: GC-MS technique is an alternative tool for the metabonomic study and would be certainly beneficial to the pathological research, early diagnosis and therapy evaluation of CRC.

[Proteomic research of biomarker of colorectal cancer metastasis].

OBJECTIVE: To explore the potential markers of colorectal cancer metastasis and the influence of 5-FU on differentially expressed proteins by using proteomic technology, and to elucidate the mechanism of colorectal cancer metastasis. METHODS: Human colorectal carcinoma cell lines of different metastatic potential, Lovo and SW480 were conventionally cultured, and the protein was extracted. 50% inhibitory concentration (IC(50)) of 5-FU to these two cell lines was measured by MTT assay. Proteins of these two cell lines after intervention by 5-FU at IC(50) were extracted, then 2-dimensional gel electrophoresis was conducted for the proteins. The differential protein spots were examined by mass spectrometry and analyzed by bioinformatics. Difference of expressed proteins in two cell lines before and after the intervention of 5-FU was validated by Western blot and immunofluorescence. RESULTS: Eleven differentially expressed proteins were identified by 2-dimensional gel electrophoresis and mass spectrometry. The hnRNP K protein and PDI were selected to be examined by Western blot and immunofluorescence. Results revealed that the expression of hnRNP K in Lovo was higher than that in SW480, while the expression of PDI was lower in Lovo. After intervention by 5-FU at IC(50), the expression of hnRNP K in Lovo decreased more as compared to SW480, while the expression of PDI in SW480 increased more as compared to Lovo. CONCLUSION: There are significant differences in expression of hnRNP K and PDI proteins between Lovo and SW480 cell lines, and the proteins alter regularly after 5-FU intervention.