Assessment by a multidisciplinary team conference affects treatment strategy and overall survival in patients with synchronous colorectal liver metastases.

BACKGROUND: The aim of this retrospective observational study was to investigate the geographical or sex differences in patients with synchronous colorectal liver metastases (sCRLM) in terms of assessment by a multidisciplinary team conference (MDT), curative treatment, and overall survival. METHOD: All sCRLM patients in the South-East Health Care Region of Sweden from 2009 to 2015 were included (n = 615). Data were derived from the Swedish Colorectal Cancer Registry, Swedish Registry of Liver and Bile Surgery and medical records. RESULTS: Patients who had a hepatobiliary unit (HBU) at the nearest hospital were more likely to undergo liver surgery (HBU+, 37% (n = 106), compared to HBU-, 22% (n = 60); p = 0.001) and had a better median survival (p < 0.001). No sex differences were observed. In multivariate Cox regression analyses of overall survival, assessment by an MDT that included a liver surgeon was independently linked to better survival (HR 0.574, 0.433-0.760). CONCLUSION: There were no sex differences in access to liver surgery or overall survival, however, there were geographical inequalities, where residency near a hospital with HBU was associated with increased overall survival and the possibility to receive liver surgery. Assessment at MDT with liver surgeon present was associated with greater survival, indicating its important role for treatment.

Clinicopathological significance of BTF3 expression in colorectal cancer.

Basic transcription factor 3 (BTF3) is a general RNA polymerase II transcription factor and is also involved in apoptosis regulation. Increasing evidence shows that BTF3 is aberrantly expressed in several kinds of malignancies, but there is no study to analyze BTF3 expression in colorectal cancer (CRC) patients. Applying immunohistochemistry, we detected BTF3 in CRCs (n = 156), the corresponding distant (n = 42), adjacent normal mucosa (n = 96), lymph node metastases (n = 35), and analyzed its relationships with clinicopathological and biological variables. Our results showed that BTF3 staining significantly increased from distant or adjacent normal mucosa to primary CRCs (p < 0.0001) or metastases (p = 0.002 and p < 0.0001). BTF3 was higher in distal cancers than in proximal cancers (57 % vs. 39 %, p = 0.041). It also showed stronger staining in primary CRCs stage I and II than that in stage III and IV (64 % vs. 35 %, p = 0.0004), or metastases (64 % vs. 29 %, p = 0.004). Cancers with better differentiation had a higher expression than those with worse differentiation (56 % vs. 37 %, p = 0.031). There were positive correlations of BTF3 expression with nuclear factor kappa B (NF-κB), RAD50, MRE11, NBS1, and AEG-1 (p < 0.05). In conclusion, BTF3 overexpression may be an early event in CRC development and could be useful biomarker for the early stage of CRCs. BTF3 has positive correlations with NF-κB, RAD50, MRE11, NBS1 and AEG-1, and might influence complex signal pathways in CRC.

Expression of AEG-1 mRNA and protein in colorectal cancer patients and colon cancer cell lines.

BACKGROUND: Astrocyte elevated gene 1 (AEG-1), an important oncogene, has been shown to be overexpressed in several types of cancers. In colorectal cancer (CRC), the protein level of AEG-1 is up-regulated in tumour tissue compared to normal mucosa, showing prognostic significance. Since little is known about the transcriptional level of AEG-1 expression and its biological pathway in CRC the aim of the present study was to examine the relationship of AEG-1 mRNA expression, the protein level and clinicopathological variables as well as its biology pathway in CRC. MATERIAL AND METHODS: The mRNA expression of AEG-1 was analysed by qPCR in fresh frozen patient samples including 156 primary tumours, along with the corresponding normal mucosa, and in five colon cancer cell lines, SW480, SW620, KM12C, KM12SM and KM12L4a. AEG-1 protein expression was investigated by immunohistochemistry in paraffin-embedded materials from 74 distant normal mucosa, 107 adjacent mucosa, 158 primary tumour, 35 lymph node metastasis and 9 liver metastasis samples. In addition, the AEG-1 protein expression was elucidated in the cell lines by Western blot. RESULTS: The lymph node metastatic cell line SW620 had a significantly higher AEG-1 mRNA (0.27 ± 0.02) expression compared to the primary tumour cell line SW480 (0.17 ± 0.04, p = 0.026). AEG-1 expression at the mRNA level and/or the protein level was significantly up-regulated gradually from normal mucosa to primary CRC, and then to lymph node metastasis and finally to liver metastasis (p < 0.05). There were significant associations of AEG-1 mRNA expression with tumour location (p = 0.047), as well as mRNA and protein expression with the tumour stage (p < 0.03). Furthermore AEG-1 protein expression was positively related to biological variables including NF-κB, p73, Rad50 and apoptosis (p < 0.05). CONCLUSION: AEG-1 is up-regulated, at the mRNA and the protein level, during CRC development and aggressiveness, and is related to tumour location and stage. It may play its role in CRC through the NF-κB signaling pathway.

NF-κB p65 phosphorylated at serine-536 is an independent prognostic factor in Swedish colorectal cancer patients.

INTRODUCTION: The NF-κB transcription factor protein family has diverse cellular and biological functions, and posttranslational modification is important to regulate these functions. An important site of phosphorylation of NF-κB p65 subunit is at serine-536 (phospho-Ser536-p65), and this phosphorylation is involved in regulation of transcriptional activity, nuclear localization, and protein stability. PATIENTS AND METHODS: In this study, we investigated expression of phospho-Ser536-p65 in colorectal cancers and its relationships with clinicopathological factors. The expression of phospho-Ser536-p65 was examined by immunohistochemistry in 203 primary colorectal cancers, 156 normal mucosa specimens, and 18 metastases in the lymph nodes. RESULTS: The expression of phospho-Ser536-p65 increased from normal mucosa to primary tumor (p < 0.0001). Further, the increased expression of phospho-Ser536-p65 in the cytoplasm of the primary tumors correlated with worse survival of the patients independently of gender, age, tumor location, stage, and differentiation (p = 0.04; hazard ratio, 1.89; 95% CI 1.03-3.47). CONCLUSION: The NF-κB p65 subunit phosphorylated at serine-536 is an independent prognostic factor in colorectal cancer patients.

Postoperative intra-arterial methylene blue injection of colorectal cancer specimens increases the number of lymph nodes recovered.

AIMS: To determine the possible advantage of intra-arterial injection of methylene blue with a view to improving lymph node recovery in postoperative examination of colorectal cancer specimens. METHODS AND RESULTS: Thirty-two colorectal cancer specimens were assigned randomly to either dissection with intra-arterial methylene blue injection or to routine dissection (without methylene blue injection). Immediately postoperatively, the specimens in the staining group were injected intra-arterially with methylene blue dye. The two procedures were compared with respect to the number of lymph nodes recovered. The number of recovered lymph nodes was significantly higher in the intra-arterial methylene blue injection group than in the group investigated with routine procedures (P<0.0001). CONCLUSION: The intra-arterial methylene blue injection method is fairly easy to use postoperatively and increases significantly the number of lymph nodes recovered in colorectal cancer specimens.

Expression of FXYD3 protein in relation to biological and clinicopathological variables in colorectal cancers.

BACKGROUND: FXYD3 is up-/down-regulated in different types of cancers. We examined FXYD3 expression in colorectal cancers and its relationship to biological and clinicopathological variables. PATIENTS AND METHODS: Expression of FXYD3 protein was immunohistochemically examined in distant normal mucosa (n = 34), adjacent normal mucosa (n = 72), primary tumour (n = 150) and lymph node metastasis (n = 35) from colorectal cancer patients. RESULTS: FXYD3 was highly expressed in primary tumour compared to adjacent normal mucosa (p = 0.02). FXYD3 was or tended to be positively related to the expression of ras (p = 0.02), p53 (p = 0.06), legumain (p = 0.02) and proliferating cell nuclear antigen (p = 0.03). Moreover, there was a higher frequency of strong FXYD3 expression in Dukes A-C tumours than in D tumours (p = 0.04). The strong FXYD3 expression tended to predict worse survival in the patients with Dukes A + B tumour (p = 0.07), while there was no such tendency in the patients with Dukes C + D tumour (p = 0.94). The tumours located in the colon had a higher degree of FXYD3 expression than the tumours located in the rectum (p = 0.05). CONCLUSION: The FXYD3 was associated with certain biological variables and may be involved in the development of the relative earlier stages of colorectal cancers.

Prognostic Heterogeneity of MRE11 Based on the Location of Primary Colorectal Cancer Is Caused by Activation of Different Immune Signals.

Background: MRE11 plays an important role in DNA damage response for the maintenance of genome stability, and is becoming a prognostic marker for cancers, including colorectal cancer (CRC). However, the correlations of MRE11 to prognosis and tumor-infiltrating inflammatory cells (TIICs) in different locations of CRC remains unclear. Methods: Among Swedish and TCGA-COREAD patients, we investigated the association of MRE11 expression, tumor-infiltrating inflammatory cells (TIICs) and microsatellite status with survival in right-sided colon cancer (RSCC) and left-sided colon and rectal cancer (LSCRC). The signaling of MRE11-related was further analyzed using weighted gene co-expression network analysis and ClueGO. Results: High MRE11 expression alone or combination of high MRE11 expression with high TIICs was related to favorable prognosis in LSCRC. Moreover, high MRE11 expression was associated with favorable prognosis in LSCRC with microsatellite stability. The relationships above were adjusted for tumor stage, differentiation, and/or TIICs. However, no such evidence was observed in RSCC. Several signaling pathways involving MRE11 were found to be associated with cell cycle and DNA repair in RSCC and LSCRC, whereas, the activation of the immune response and necrotic cell death were specifically correlated with LSCRC. Conclusions: High MRE11 expression is an independent prognostic marker in LSCRC and enhanced prognostic potency of combining high MRE11 with high TIICs in LSCRC, mainly due to differential immune signaling activated by MRE11 in RSCC and LSCRC, respectively.

The different roles of hRAD50 in microsatellite stable and unstable colorectal cancers.

RAD50 protein is essential for DNA double-strand break repair and maintaining genomic integrity. In this study, we investigated the clinicopathological significance of hRAD50 expression and mutation in microsatellite stable (MSS) and unstable (MSI) colorectal cancers (CRCs). hRAD50 expression was examined in primary CRC (n=268), the corresponding distant (n=69) and adjacent normal mucosa (n=138), and lymph node metastasis (n=44) by immunohistochemistry. hRAD50 mutation was analyzed in 87 primary CRCs by PCR-SSCP-DNA sequencing. hRAD50 expression was increased in MSS primary CRCs, but not MSI ones, compared with distant/adjacent normal mucosa (p<0.05). There was no difference in the hRAD50 expression between primary and metastatic CRCs. The increased hRAD50 expression in MSS primary CRCs was related (p<0.05) or tended to be related (p=0.05) to early tumor stage, better differentiation, high inflammatory infiltration, p53 overexpression. Frameshift mutations of (A)(9) at coding region of hRAD50 were only found in MSI CRCs. Our results suggest that hRAD50 may play different roles in the development of MSS and MSI CRCs: increased hRAD50 expression in MSS CRCs {may be a cellular response against tumor from further progression}, while hRAD50 mutation may be involved in the development of MSI CRCs.

MANBA polymorphism was related to increased risk of colorectal cancer in Swedish but not in Chinese populations.

beta-mannosidase, encoded by MANBA, has been suggested to be implicated in cancers, while genetic variations in the MANBA in relation to colorectal cancer (CRC) risk has not been examined. In this study, we investigated the relationship of a polymorphic CA repeat in MANBA gene with CRC risk in 152 Swedish CRC patients and 441 Swedish controls, and 196 Chinese CRC patients and 577 Chinese controls, as well as the clinicopathologic significance of this polymorphism on CRC patients, by using capillary electrophoresis. The MANBA genotypes were related to CRC risk in the Swedish population (p=0.03), but not in the Chinese population. In the Swedish population, individuals with < 22 CAs/< 22 CAs had significantly increased risk for CRC compared with those with >or=22 CAs/>or= 22 CAs (gender-age-adjusted analysis: OR 1.93, 95% CI 1.06-3.51). There was no relationship between the polymorphism and clinicopathologic variables. These findings suggest the different susceptibilities of this polymorphism to CRC development in the two populations.

Assessment of remaining tumour involved lymph nodes with MRI in patients with complete luminal response after neoadjuvant treatment of rectal cancer.

OBJECTIVE: To assess the accuracy of MRI to predict remaining lymph node metastases in patients with complete pathological luminal response (ypT0) after neoadjuvant therapy. METHODS: Data from a national registry were used. 19 patients with histopathologically remaining lymph node metastases (ypT0N+) were identified. Another 19 patients without lymph node metastases (ypT0N0) were used as matched controls. Two radiologists blinded to all patient information evaluated staging and restaging MRI that was compared to histopathological findings of the resected specimen. RESULTS: The average size of the largest lymph node on restaging MRI was significantly larger (4.5 mm) in the ypT0N+ group than in the ypT0N0 group (2.6 mm) (p = 0.04). Presence of ypN+ was correctly predicted by MRI in 7 of 19 patients. In patients without lymph node metastases (ypT0N0), these were correctly classified by MRI in 16 of 19 patients. All patients who had MR-identified lymph nodes larger than 8 mm at restaging were ypTN+. The sensitivity, specificity, positive predictive value and negative for prediction of remaining lymph node metastasis with MRI were 37, 84, 70 and 57%. CONCLUSION: In patients with ypT0 in rectal cancer after neoadjuvant treatment, remaining regional lymph node metastases cannot safely be predicted by restaging MRI alone using presently known criteria. Presence of a lymph node over 8 mm on restaging MRI strongly indicates yPN+. Advances in knowledge: This is one of the first studies on MRI lymph node assessment after chemo-radiotherapy (CRT) in luminal complete response.

Expression of MAC30 protein is related to survival and biological variables in primary and metastatic colorectal cancers.

MAC30 is highly expressed in several types of tumors including colorectal cancers, however, its clinicopathological and biological significance in colorectal cancers is currently not known. The aim of our study was to investigate MAC30 expression in distant normal mucosa, adjacent normal mucosa, primary tumors and metastases of colorectal cancer, and to determine the relationship between MAC30 expression and clinicopathological and biological variables. MAC30 expression was immunohistochemically examined in distant normal mucosa (n = 54), adjacent normal mucosa (n = 123), primary tumors (n = 217) and lymph node metastases (n = 56) from colorectal cancer patients. MAC30 cytoplasmic expression was increased from distant normal mucosa to primary tumor and to metastasis (p < 0.0001-0.04). Furthermore, 40% primary and 37% metastatic tumors showed stronger cytoplasmic expression of MAC30 at the tumor invasive margins compared to inner tumor areas. Strong cytoplasmic expression of MAC30 in the metastasis was related to a poor prognosis (p = 0.04). MAC30 cytoplasmic expression was positively related to expression of proliferating cell nuclear antigen (p = 0.04), p53 (p = 0.04), nucleoporin 88 (p = 0.001), legumain (p = 0.004) and particularly interesting new cysteine-histidine rich protein (p = 0.004). However, MAC30 expression in the nucleus and stroma did not have any clinicopathological and biological significance (p > 0.05). In conclusion, MAC30 protein may play a role in development of colorectal cancer, and can be considered as a prognostic factor.

Legumain expression in relation to clinicopathologic and biological variables in colorectal cancer.

PURPOSE: Legumain, a novel asparaginyl endopeptidase, has been observed to be highly expressed in several types of tumors including colorectal cancer. However, there is no study examining the relationship of legumain expression to clinocopathologic and biological variables in colorectal cancers. EXPERIMENTAL DESIGN: We investigated legumain expression in 164 primary colorectal cancers, 34 corresponding distant normal mucosa samples, 89 adjacent normal mucosa samples, and 33 lymph node metastases using immunohistochemistry. We also did Western blotting analysis on three additional colorectal cancers and three colonic cell lines. RESULTS: Legumain expression was increased in primary tumors compared with distant or adjacent normal mucosa (P < 0.05), but there was no significant change between primary tumors and metastases (P > 0.05). Legumain expression was positively related to poorer differentiation/mucinous carcinoma (P = 0.04), higher degree of necrosis (P = 0.03) and apoptosis (P < 0.0001), positive proliferating cell nuclear antigen (P < 0.0001) and p53 expression (P = 0.049), and had a positive tendency towards stromelysin 3 (P = 0.058) and PINCH positivity (P = 0.05). The patients with tumors that showed both weak and lower percentage of the legumain expression, either in tumor (P = 0.01) or in stroma (P = 0.04), had a better prognosis. CONCLUSIONS: The legumain expression may be involved in colorectal cancer development and have a prognostic value in the patients.

FXYD-3 expression in relation to local recurrence of rectal cancer.

PURPOSE: In a previous study, the transmembrane protein FXYD-3 was suggested as a biomarker for a lower survival rate and reduced radiosensitivity in rectal cancer patients receiving preoperative radiotherapy. The purpose of preoperative irradiation in rectal cancer is to reduce local recurrence. The aim of this study was to investigate the potential role of FXYD-3 as a biomarker for increased risk for local recurrence of rectal cancer. MATERIALS AND METHODS: FXYD-3 expression was immunohistochemically examined in surgical specimens from a cohort of patients with rectal cancer who developed local recurrence (n = 48). The cohort was compared to a matched control group without recurrence (n = 81). RESULTS: Weak FXYD-3 expression was found in 106/129 (82%) of the rectal tumors and strong expression in 23/129 (18%). There was no difference in the expression of FXYD-3 between the patients with local recurrence and the control group. Furthermore there was no difference in FXYD-3 expression and time to diagnosis of local recurrence between patients who received preoperative radiotherapy and those without. CONCLUSION: Previous findings indicated that FXYD-3 expression may be used as a marker of decreased sensitivity to radiotherapy or even overall survival. We were unable to confirm this in a cohort of rectal cancer patients who developed local recurrence.

Noxa in colorectal cancer: a study on DNA, mRNA and protein expression.

Noxa is a BH3-only member of the Bcl-2 family, upregulated by p53 as a response to DNA damage. Mutations in the BH3-only region of other BH3-only members lead to an inactive protein. We have investigated the mRNA expression of Noxa with real-time PCR in 94 unselected colorectal adenocarcinomas and the corresponding normal mucosa. Among them, Noxa protein expression was investigated with immunohistochemistry in 16 tumors and six corresponding normal mucosa samples. Further, we searched for Noxa mutations in all the cases using single-stranded conformation polymorphism and DNA sequencing. The mRNA expression of Noxa was weak in 9% and strong in 2% of the tumors, and decreased in 9% and increased in 16% of the tumors compared with the normal mucosa; however, these changes did not have any clinical or pathological significance. The protein level in most of the cases investigated was correlated with the mRNA level. We did not find any mutations in the Noxa gene. Thus, we suggest that Noxa may not be of importance in the development of colorectal cancer.

Polymorphisms in sulfotransferase 1A1 and glutathione S-transferase P1 genes in relation to colorectal cancer risk and patients' survival.

AIM: To examine whether polymorphisms in SULT1A1 and GSTP1 genes contribute to colorectal cancer development and whether they are associated with clinicopathological variables are not well identified. METHODS: We examined the genotypes of 125 colorectal cancer patients and 666 healthy controls in a Swedish population by using PCR-restriction fragment length polymorphism (RFLP). RESULTS: SULT1A1 *2/*2 genotype (OR=2.49, 95%CI=1.48-4.19, P=0.0002) and *2 allele (OR=1.56, 95%CI=1.16-2.10, P=0.002) had an effect on colorectal cancer susceptibility, while GSTP1 genotype was without effect. However, GSTP1 G-type predicted a worse prognosis in the patients independently of gender, age, Dukes' stage, growth pattern, and differentiation (P=0.03). CONCLUSION: Polymorphism in SULT1A1 may predispose to colorectal cancer and GSTP1 may be a biological indicator of prognosis in the patients.

Relationships of tumor inflammatory infiltration and necrosis with microsatellite instability in colorectal cancers.

AIM: The relationships between microsatellite instability (MSI) and survival in colorectal cancer patients are not consistent. The favorable survival of patient with MSI has been suggested to be related to pronounced inflammatory infiltration; however, the reason for non-association of MSI with survival is unclear. Our aims were to investigate the associations of inflammatory infiltration and tumor necrosis (TN) with microsatellite status and clinicopathological factors in colorectal cancer patients in whom MSI was not related to survival. METHODS: Three hundred and one colorectal adenocarcinomas were evaluated for inflammatory infiltration and 300 for TN under light microscope. RESULTS: Low infiltration at invasive margin (chi2 = 3.94, P = 0.047) and in whole tumor stroma (chi2 = 3.89, P = 0.049) was associated with MSI, but TN was not (chi2=0.10, P = 0.75). Low infiltration was related to advanced stage (chi2 = 8.67, P = 0.03), poorer differentiation (chi2 = 8.84, P = 0.03), DNA non-diploid (chi2 = 10.04, P = 0.002), higher S-phase fraction (chi2 = 11.30, P = 0.004), positive p53 expression (chi2 = 7.94, P = 0.01), and worse survival (P = 0.03 for both univariate and multivariate analyses). Abundant TN was related to advanced stage (chi2 = 17.74, P = 0.001) and worse survival (P = 0.02 for univariate, and P = 0.05 for multivariate analysis). CONCLUSION: The result that high inflammatory infiltration was not related to MSI might help explain the non-association of MSI with survival in colorectal cancer patients.

Orally Administered Trimethoprim-Sulfamethoxazole and Metronidazole as Infection Prophylaxis in Elective Colorectal Surgery.

BACKGROUND: This randomized clinical trial evaluated orally administered trimethoprim-sulfamethoxazole and metronidazole (TSM) in elective colorectal surgery as prophylactic for post-operative surgical site infections (SSI). METHODS: Patients undergoing elective colorectal resection were evaluated for inclusion. Randomized subjects received either orally administered TSM or intravenously administered cefuroxime and metronidazole (control group, CXM). The primary endpoint was the rate of SSI. RESULTS: A total of 1073 subjects were randomized to either control (540) or TSM (533). 486 patients in the TSM group and 499 in the control group were followed-up with after 4 weeks. Thirty-seven (3.8%) patients were afflicted by SSI at discharge from hospital and 69 (7.0%) at follow-up four weeks after surgery. After four weeks, the rate of incisional SSI was 7.0% in the TSM group and 3.6% in the control group (p=0.022). For organ/space SSI and the other complications monitored in the study, no differences were observed between the groups. CONCLUSION: Orally administered TSM as prophylaxis before elective colorectal surgery results in a low rate of organ/space SSI but an increased rate of incisional SSI compared with intravenously administered cefuroxime and metronidazole. Thus, when considering orally administered TSM, because of environmental concerns or for economic reasons, the slightly increased infection rate has to be kept in mind.

Prognostic Significance and Molecular Features of Colorectal Mucinous Adenocarcinomas: A Strobe-Compliant Study.

Mucinous adenocarcinoma (MC) is a special histology subtype of colorectal adenocarcinoma. The survival of MC is controversial and the prognostic biomarkers of MC remain unclear. To analyze prognostic significance and molecular features of colorectal MC. This study included 755,682 and 1001 colorectal cancer (CRC) patients from Surveillance, Epidemiology, and End Results program (SEER, 1973-2011), and Linköping Cancer (LC, 1972-2009) databases. We investigated independently the clinicopathological characteristics, survival, and variety of molecular features from these 2 databases. MC was found in 9.3% and 9.8% patients in SEER and LC, respectively. MC was more frequently localized in the right colon compared with nonmucinous adenocarcinoma (NMC) in both SEER (57.7% vs 37.2%, P < 0.001) and LC (46.9% vs 27.7%, P < 0.001). Colorectal MC patients had significantly worse cancer-specific survival (CSS) than NMC patients (SEER, P < 0.001; LC, P = 0.026), prominently in stage III (SEER, P < 0.001; LC, P = 0.023). The multivariate survival analysis showed that MC was independently related to poor prognosis in rectal cancer patients (SEER, hazard ratios [HR], 1.076; 95% confidence intervals [CI], 1.057-1.096; P < 0.001). In LC, the integrated analysis of genetic and epigenetic features showed that that strong expression of PINCH (HR, 3.954; 95% CI, 1.493-10.47; P = 0.013) and weak expression of RAD50 (HR 0.348, 95% CI, 0.106-1.192; P = 0.026) were significantly associated with poor CSS of colorectal MC patients. In conclusion, the colorectal MC patients had significantly worse CSS than NMC patients, prominently in stage III. MC was an independent prognostic factor associated with worse survival in rectal cancer patients. The PINCH and RAD50 were prognostic biomarkers for colorectal MC patients.

MicroRNA Expression Profile Reveals miR-17-92 and miR-143-145 Cluster in Synchronous Colorectal Cancer.

The expression of abnormal microRNA (miRNA, miR) is a ubiquitous feature of colorectal cancer (CRC). The pathological features and clinical behaviors of synchronous CRC have been comprehensively described; however, the expression profile of miRNA and small nucleolar RNA (snoRNA) in synchronous CRC has not been elucidated. In the present study, the expression profile of miRNA and snoRNA in 5 synchronous CRCs, along with the matched normal colorectal tissue was evaluated by microarray. Function and pathway analyses of putative targets, predicted from miRNA-mRNA interaction, were performed. Moreover, we analyzed clinicopathological and molecular characteristics of 22 patients with synchronous CRC and 579 solitary CRCs in a retrospective cohort study. We found a global dysregulation of miRNAs, including an oncogenic miR-17-92 cluster and oncosuppressive miR-143-145 cluster, and snoRNAs in synchronous CRC. Differential miRNA rather than snoRNA expression was robust enough to distinguish synchronous cancer from normal mucosa. Function analysis of putative targets suggested that miRNA clusters may modulate multiple effectors of oncogenic pathways involved in the pathogenesis of synchronous CRC. A comparison of normal mucosa between synchronous and solitary CRC suggested a differential genetic background of synchronous CRC from solitary CRC during carcinogenesis. Compared with solitary cancer patients, synchronous cases exhibited multiple extra-colonic cancers (P = 0.012), coexistence of adenoma (P = 0.012), microsatellite instability (P = 0.024), and less glucose transporter 1 (P = 0.037). Aberrant miRNA expression profiles could potentially be used as a diagnostic tool for synchronous CRC. Our findings represent the first comprehensive miRNA and snoRNA expression signatures for synchronous CRC, implicating that the miRNAs and snoRNAs may present therapeutic targets for synchronous CRC.