Cancer-associated fibroblasts at the unfavorable desmoplastic stroma promote colorectal cancer aggressiveness: Potential role of ADAM9.

The tumor microenvironment plays a key role in cancer aggressiveness. Desmoplastic reaction (DR), morphologically classified as Mature, Intermediate and Immature types, has previously been shown to be highly prognostic in colorectal cancer (CRC) and it consists to a large extent of cancer-associated fibroblasts (CAFs). The aim of our study was to characterize the molecular background of DR and understand the effects of CAFs in tumor aggressiveness. The prognostic significance of DR was initially examined in 1497 patients. Then CAFs originating from patient tissues with different DR types were isolated and their impact on tumor growth was examined both in vitro and in vivo. DR was shown to be highly prognostic, with patients within the Immature DR group conferring the worst relapse-free survival. The conditioned media of CAFs from tumor with Immature-type DR (CAFsImmature ) significantly increased proliferation and migration of CRC cell lines and growth of CRC-derived organoids compared to that of CAFs from Mature-type DR (CAFsMature ). Subcutaneous or orthotopic implantation of CRC cells together with CAFsImmature in mice significantly promoted tumor growth and dissemination compared to implantation with CAFsMature . Systematic examination of the expression of "a disintegrin and metalloproteinases" (ADAMs) in CAFs isolated from CRC tissues showed that the secreted isoform of ADAM9 (ADAM9s) was significantly higher in CAFsImmature than in CAFsMature . Knockdown of ADAM9s in CAFsImmature abrogated the promoting effects on CRC cell proliferation and migration. CAFs-derived ADAM9s is implicated in deteriorating survival in CRC patients with Immature-type DR by increasing tumor cell proliferation and dissemination.

Proposal for a tumor budding predictive score derived from endoscopic biopsy samples in colorectal cancer.

BACKGROUND: In colorectal cancer, tumor budding is highlighted as both a prognostic indicator and a predictor of chemosensitivity. However, tumor budding has a serious drawback because of unattainable preoperative assessment, thereby, making it not applicable to decision-making on treatment strategies. Recently, high expressions of seven genes (i.e., MSLN, SLC4A11, WNT11, SCEL, RUNX2, MGAT3, and FOXC1) were shown to be associated with high-budding colorectal cancers. This study aimed to propose a budding prediction system using selected RNAs extracted from biopsy specimens. METHODS: The RNA expression levels in 86 surgically resected samples and in 104 samples obtained by colonoscopy before surgery were investigated. RESULTS: The tumor surface expressions of four exclusive genes (i.e., MSLN, SLC4A11, SCEL, and MGAT3) were correlated with the tumor budding grade. Subsequently, the logit P value calculated by multiple logistic regression analysis using the four surface gene expressions was set as the following budding predictive score: Logit (P) = - 0.55 + 0.27*MSLN + 0.16*SLC4A11 + 0.06*MGAT3 + 0.21*SCEL. The effectiveness of the model using colorectal cancer biopsy samples was well corroborated prospectively. CONCLUSION: The budding predictive score that we developed using endoscopic biopsy specimens was clarified to have a high potential for preoperative use.

Mesothelin Expression is Correlated with Chemoresistance in Stage IV Colorectal Cancer.

BACKGROUND: Mesothelin (MSLN) is a cell-surface glycoprotein present on mesothelial cells; its expression in several epithelial cancers generally portends an unfavorable prognosis. We investigated MSLN as a surrogate chemopredictive biomarker and examined the impact of MSLN expression in stage IV colorectal cancer (CRC). METHODS: We recruited 254 patients with CRC who received systemic chemotherapy following primary tumor resection between 2000 and 2019. Resected specimens were immunostained for MSLN and stratified by MSLN expression. The associations of tumor MSLN expression with tumor response in metastatic lesions and survival were evaluated. RESULTS: Of the 247 patients with stage IV CRC, 41 (16.1%) and 213 (83.9%) had high and low MSLN expression, respectively. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, the investigator-assessed objective response rate was 22.0% in the high MSLN expression group and 45.5% in the low MSLN expression group (p = 0.0050). The disease control rates in these groups were 65.9% and 85.9%, respectively (p = 0.00019). In the patients with high MSLN expression, the conversion rate among those with initially unresectable metastases was 0% versus 14% in the patients with low MSLN expression (p = 0.0053). The median overall survival (OS) was 1.5 years (95% confidence interval [CI] 1.1-2.8) in the high MSLN expression group versus 2.6 years (95% CI 2.2-3.0) in the low MSLN expression group. The 3-year OS rates in these groups were 23.5 and 41.5%, respectively (p = 0.0120). CONCLUSIONS: High MSLN expression is correlated with chemoresistance and poor prognoses in stage IV CRC.

Clinical Significance of a Gene Signature Generated from Tumor Budding Grade in Colon Cancer.

BACKGROUND: Tumor budding, a microscopic finding of dedifferentiation at the invasive margin, has been reported as a definite prognostic marker in colon cancer (CC). Herein, we aimed to generate a molecular budding signature (MBS) based on DNA microarray data and to examine its prognostic significance. METHODS: Frozen tissue samples from 85 patients with stage II/III CC were used for DNA microarray analyses. First, we selected candidate genes that were differentially expressed (twofold change) between the invasive frontal regions and corresponding tumor centers of three extremely high-grade budding tumors. Subsequently, using microarray data from whole-tissue sections of the 85 patients, we selected MBS-constituent genes from the candidates based on correlation to the pathological budding grade. The MBS score was calculated using the sum of the logarithm of the expression of each gene. RESULTS: We selected seven MBS-constituent genes: MSLN, SLC4A11, WNT11, SCEL, RUNX2, MGAT3, FOXC1. A comparison of relapse-free survival (RFS) rates revealed a significant impact of the MBS score [5-year RFS, 77.4% (score-high) vs. 95.1% (score-low); P = 0.044]. Analyses of public databases revealed that low MBS score patients exhibited better prognosis than those with high-score cancers (GSE14333: 5-year RFS, 83.1% vs. 66.6%, P = 0.028; GSE39582: 5-year disease-free survival, 72.2% vs. 58.1%, P = 0.0005). Multivariate analysis revealed that the MBS score is an independent prognostic indicator in GSE39582 (hazard ratio, 1.611; P = 0.013). CONCLUSIONS: We developed a new gene classification method, i.e., MBS, and demonstrated its clinical relevance as an indicator of high recurrence risk of CC.

Japanese Versus Non-Japanese Patients with Transient Ischemic Attack or Minor Stroke: Subanalysis of TIA registry.org.

BACKGROUND: TIAregistry.org is an international cohort of patients with transient ischemic attack (TIA) or minor stroke within 7 days before enrollment in the registry. Main analyses of 1-year follow-up data have been reported.5 We conducted subanalysis on the baseline and 1-year follow-up data of Japanese patients. METHODS: The patients were classified into 2 groups based on Japanese ethnicity, Japanese (345) and non-Japanese (3238), and their baseline data and 1-year event rates were compared. We also determined risk factors and predictors of 1-year stroke. RESULTS: Current smoking, regular alcohol drinking, intracranial arterial stenosis, and small vessel occlusion; and hypertension, dyslipidemia, coronary artery disease, and extracranial arterial stenosis were more and less common among Japanese patients, respectively. Stroke risk was higher and TIA risk was lower at 1-year follow-up among Japanese patients. The baseline risk factors for recurrent stroke were diabetes, alcohol drinking, and large artery atherosclerosis. Independent predictors of 1-year stroke risk were prior congestive heart failure and alcohol consumption. CONCLUSIONS: The two populations of patients featured differences in risk factors, stroke subtypes, and outcome events. Predictors of recurrent stroke among Japanese patients included congestive heart failure and regular alcohol drinking. Strategies to attenuate residual risk of stroke aside from adherence to current guidelines should take our Japanese-patient specific findings into account.

Incorporating post-translational modifications and unnatural amino acids into high-throughput modeling of protein structures.

MOTIVATION: Accurately predicting protein side-chain conformations is an important subproblem of the broader protein structure prediction problem. Several methods exist for generating fairly accurate models for moderate-size proteins in seconds or less. However, a major limitation of these methods is their inability to model post-translational modifications (PTMs) and unnatural amino acids. In natural living systems, the chemical groups added following translation are often critical for the function of the protein. In engineered systems, unnatural amino acids are incorporated into proteins to explore structure-function relationships and create novel proteins. RESULTS: We present a new version of SIDEpro to predict the side chains of proteins containing non-standard amino acids, including 15 of the most frequently observed PTMs in the Protein Data Bank and all types of phosphorylation. SIDEpro uses energy functions that are parameterized by neural networks trained from available data. For PTMs, the [Formula: see text] and [Formula: see text] accuracies are comparable with those obtained for the precursor amino acid, and so are the RMSD values for the atoms shared with the precursor amino acid. In addition, SIDEpro can accommodate any PTM or unnatural amino acid, thus providing a flexible prediction system for high-throughput modeling of proteins beyond the standard amino acids. AVAILABILITY AND IMPLEMENTATION: SIDEpro programs and Web server, rotamer libraries and data are available through the SCRATCH suite of protein structure predictors at http://scratch.proteomics.ics.uci.edu/

[Alzheimer's disease and vascular dementia].

Alzheimer's disease (AD) and vascular dementia (VaD) are the two major forms of dementia in the elderly, and they had been separated categorically on the basis of pathogenetic mechanisms and clinical operationalized criteria. However, it was claimed that this strict separation might steered toward the overdiagnosis of vascular dementia, this dichotomy has been reevaluated in the light of recent epidemiological and neuropathological knowledge. Cerebrovascular disease (CVD) is now considered as one of the vascular risk factors to the onset and evolution of Alzheimer's disease. Futhermore, the term "AD with CVD" has been used to classify patients fulfilling the clinical criteria for possible AD and who also present clinical or brain imaging evidence of relevant CVD.

Localized colorectal cancer database integrating 4 randomized controlled trials; (JCOG2310A).

Although phase III randomized controlled trials (RCTs) represent the most robust statistical approach for answering clinical questions, they require massive expenditures in terms of time, labor, and funding. Ancillary and supplementary analyses using RCTs are sometimes conducted as alternative approaches to answering clinical questions, but the available integrated databases of RCTs are limited. In this background, the Colorectal Cancer Study Group (CCSG) of the Japan Clinical Oncology Group (JCOG) established a database of ancillary studies integrating four phase III RCTs (JCOG0212, JCOG0404, JCOG0910 and JCOG1006) conducted by the CCSG to investigate specific clinicopathological factors in pStage II/III colorectal cancer (JCOG2310A). This database will be updated by adding another clinical trial data and accelerating several analyses that are clinically relevant in the management of localized colorectal cancer. This study describes the details of this database and planned and ongoing analyses as an initiative of JCOG cOlorectal Young investigators (JOY).

Deep architectures for protein contact map prediction.

MOTIVATION: Residue-residue contact prediction is important for protein structure prediction and other applications. However, the accuracy of current contact predictors often barely exceeds 20% on long-range contacts, falling short of the level required for ab initio structure prediction. RESULTS: Here, we develop a novel machine learning approach for contact map prediction using three steps of increasing resolution. First, we use 2D recursive neural networks to predict coarse contacts and orientations between secondary structure elements. Second, we use an energy-based method to align secondary structure elements and predict contact probabilities between residues in contacting alpha-helices or strands. Third, we use a deep neural network architecture to organize and progressively refine the prediction of contacts, integrating information over both space and time. We train the architecture on a large set of non-redundant proteins and test it on a large set of non-homologous domains, as well as on the set of protein domains used for contact prediction in the two most recent CASP8 and CASP9 experiments. For long-range contacts, the accuracy of the new CMAPpro predictor is close to 30%, a significant increase over existing approaches. AVAILABILITY: CMAPpro is available as part of the SCRATCH suite at http://scratch.proteomics.ics.uci.edu/. CONTACT: pfbaldi@uci.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Impact of cognitive impairment on clinical outcomes in elderly patients with atrial fibrillation: ANAFIE Registry.

Background: This subcohort study of All Nippon AF In the Elderly (ANAFIE) Registry based on 33 275 elderly patients (aged ≥75 years) with non-valvular atrial fibrillation (NVAF) investigated the relationship between cognitive function and 2-year clinical outcomes. Methods: A total of 2963 (mean age, 81.4 years) patients participated in this subcohort study and were classified as having normal cognition (Mini-Mental State Examination (MMSE) score ≥24/30) or cognitive impairment (score ≤23/30) at baseline. Patients with a decrease of >2 points after 24 months were classified as having cognitive decline. Results: At baseline, 586 (19.8%) patients had cognitive impairment. These patients tended to be older and had poorer general conditions than patients with normal cognition. The 2-year probability of stroke/systemic embolic events (SEEs), major bleeding and intracranial haemorrhage was numerically higher; those of cardiovascular death, all-cause death and net clinical outcome (composite of stroke/SEE, major bleeding and all-cause death) were significantly higher (all p<0.001) in patients with cognitive impairment versus normal cognition. In multivariate analysis, the risks of cardiovascular death (p=0.021), all-cause death (p<0.001) and net clinical outcome (p<0.001) were higher in patients with cognitive impairment versus those with normal cognition. After 24 months, 642 of 1915 (33.5%) patients with repeated MMSE determination had cognitive decline. Educational background <9 years, older age and concomitant cerebrovascular disorders were significant risk factors of cognitive decline at the 2-year follow-up. Conclusions: Elderly patients with NVAF with cognitive impairment have a higher mortality risk than those with normal cognition. Several significant risk factors of cognitive decline were identified at 2-year follow-up. Trial registration number: UMIN000024006 (http://www.umin.ac.jp/).

SIDEpro: a novel machine learning approach for the fast and accurate prediction of side-chain conformations.

Accurate protein side-chain conformation prediction is crucial for protein modeling and existing methods for the task are widely used; however, faster and more accurate methods are still required. Here we present a new machine learning approach to the problem where an energy function for each rotamer in a structure is computed additively over pairs of contacting atoms. A family of 156 neural networks indexed by amino acid and contacting atom types is used to compute these rotamer energies as a function of atomic contact distances. Although direct energy targets are not available for training, the neural networks can still be optimized by converting the energies to probabilities and optimizing these probabilities using Markov Chain Monte Carlo methods. The resulting predictor SIDEpro makes predictions by initially setting the rotamer probabilities for each residue from a backbone-dependent rotamer library, then iteratively updating these probabilities using the trained neural networks. After convergences of the probabilities, the side-chains are set to the highest probability rotamer. Finally, a post processing clash reduction step is applied to the models. SIDEpro represents a significant improvement in speed and a modest, but statistically significant, improvement in accuracy when compared with the state-of-the-art for rapid side-chain prediction method SCWRL4 on the following datasets: (1) 379 protein test set of SCWRL4; (2) 94 proteins from CASP9; (3) a set of seven large protein-only complexes; and (4) a ribosome with and without the RNA. Using the SCWRL4 test set, SIDEpro's accuracy (χ(1) 86.14%, χ(1+2) 74.15%) is slightly better than SCWRL4-FRM (χ(1) 85.43%, χ(1+2) 73.47%) and it is 7.0 times faster. On the same test set SIDEpro is clearly more accurate than SCWRL4-rigid rotamer model (RRM) (χ(1) 84.15%, χ(1+2) 71.24%) and 2.4 times faster. Evaluation on the additional test sets yield similar accuracy results with SIDEpro being slightly more accurate than SCWRL4-flexible rotamer model (FRM) and clearly more accurate than SCWRL4-RRM; however, the gap in CPU time is much more significant when the methods are applied to large protein complexes. SIDEpro is part of the SCRATCH suite of predictors and available from: http://scratch.proteomics.ics.uci.edu/.

Dabigatran and factor Xa inhibitors for stroke prevention in patients with nonvalvular atrial fibrillation.

Stroke is a major health problem worldwide, and is often fatal or associated with poor long-term outcomes. Atrial fibrillation (AF) is responsible for up to 20% of all strokes; and the risk of stroke in patients with AF increases with age. Although warfarin is well established for the prevention of stroke in patients with AF, it has some limitations, particularly a narrow therapeutic window, variable/unpredictable pharmacokinetic/pharmacodynamic properties, the restriction of vitamin K intake, and the need for regular coagulation monitoring. Therefore, warfarin is underused for stroke prevention in patients with AF. Several anticoagulants that inhibit thrombin or factor Xa have been developed. Dabigatran is a direct thrombin (factor IIa) inhibitor that overcomes many of the limitations associated with warfarin. The recent Randomized Evaluation of Long Term Anticoagulant Therapy study showed the noninferiority of 110 mg and 150 mg dabigatran twice daily, and the superiority of 150 mg dabigatran twice daily versus adjusted-dose warfarin in the prevention of stroke or systemic embolism in patients with nonvalvular AF. In addition, the rate of intracranial hemorrhage was much lower with both doses of dabigatran than with warfarin. Dabigatran was recently approved in Japan for the prevention of ischemic stroke and systemic embolism in patients with nonvalvular AF. Therefore, in this review, we discuss the properties of dabigatran and its clinical efficacy, safety, and positioning in the prevention of stroke. We also discuss precautions for the use of dabigatran and future perspectives with a view to reducing the risk of stroke with new oral anticoagulants, including factor Xa inhibitors in AF patients.

Musical anhedonia: selective loss of emotional experience in listening to music.

Recent case studies have suggested that emotion perception and emotional experience of music have independent cognitive processing. We report a patient who showed selective impairment of emotional experience only in listening to music, that is musical anhednia. A 71-year-old right-handed man developed an infarction in the right parietal lobe. He found himself unable to experience emotion in listening to music, even to which he had listened pleasantly before the illness. In neuropsychological assessments, his intellectual, memory, and constructional abilities were normal. Speech audiometry and recognition of environmental sounds were within normal limits. Neuromusicological assessments revealed no abnormality in the perception of elementary components of music, expression and emotion perception of music. Brain MRI identified the infarct lesion in the right inferior parietal lobule. These findings suggest that emotional experience of music could be selectively impaired without any disturbance of other musical, neuropsychological abilities. The right parietal lobe might participate in emotional experience in listening to music.

Postoperative pneumonia causes the loss of skeletal muscle volume and poor prognosis in patients undergoing esophagectomy for esophageal cancer.

PURPOSES: This retrospective study investigated the effect of postoperative pneumonia on the loss of skeletal muscle volume after esophagectomy for esophageal cancer. METHODS: A total of 123 patients who had undergone esophagectomy for esophageal cancer and had (30 patients) or did not have (93 patients) postoperative pneumonia were included in the analysis. The association of clinicopathological characteristics with loss of skeletal muscle volume and long-term survival were evaluated in patients with or without postoperative pneumonia. RESULTS: There were no differences in the psoas muscle volume index (PI), lymphocyte count, serum albumin level, or prognostic nutritional index between the two groups both preoperatively and at 6 months after surgery. The decrease in PI at 6 months after surgery was significant in patients with postoperative pneumonia (- 9.9 ± 2.5%) but not in those without pneumonia (- 2.6 ± 1.6%). Patients with postoperative pneumonia had a significantly increased frequency of asymptomatic pneumonia at 6 months after surgery compared with those who did not have postoperative pneumonia (36.7% vs. 19.4%). Overall survival was significantly poorer in patients with postoperative pneumonia than in those without pneumonia (p < 0.05). CONCLUSIONS: Postoperative pneumonia was associated with the loss of skeletal muscle volume and asymptomatic pneumonia within 6 months of surgery as well as poorer overall survival.

Japanese and Non-Japanese Patients with Transient Ischemic Attack or Minor Stroke: A Five-Year Risk Analysis of Stroke and Vascular Events.

AIMS: We have previously reported 5-year follow-up data on the TIAregistry.org, an international prospective cohort in patients with transient ischemic attack (TIA) or minor stroke. We conducted a Japanese subgroup analysis because outcomes and predictors might differ according to ethnicities and regions. In this study, we compared the baseline and 5-year follow-up data of Japanese and non-Japanese patients with TIA or minor stroke. METHODS: Patients with TIA or minor ischemic stroke within 7 days after the onset were classified into two groups based on ethnicity, Japanese (n=345) and non-Japanese (n=3502); further, 5-year event rates were compared between the two groups. We also determined predictors of 5-year stroke for both groups. RESULTS: Vascular death and death from any cause were identified to be less prevalent, unlike stroke and intracranial hemorrhage, which was determined to be more prevalent in Japanese than in non-Japanese patients. Five-year rate of stroke was significantly higher in Japanese patients. Cumulative stroke and major cardiovascular event rates did not decline but instead linearly increased from 1 to 5 years in both groups. Baseline risk factors for 5-year stroke were as follows: age, diabetes, history of stroke or TIA, and congestive heart failure in Japanese patients. Independent predictors of 5-year stroke were large artery atherosclerosis, congestive heart failure, diabetes, and age in Japanese patients. CONCLUSIONS: Recurrent stroke and intracranial hemorrhage were determined to be more prevalent at 5 years after TIA or minor stroke in Japanese patients than in non-Japanese patients. Strategies to mitigate the long-term risks of stroke, aside from adherence to current guidelines, should take Japanese-patient-specific residual risks into account.

Co-expression of mesothelin and CA125/MUC16 is a prognostic factor for breast cancer, especially in luminal-type breast cancer patients.

The expression of mesothelin correlates with a poor prognosis in patients with breast cancer. Since mesothelin plays a role in cancer metastasis in association with CA125, we herein examined the expression of mesothelin and CA125, and the clinicopathological meaning and prognosis of the co-expression of mesothelin and CA125 in breast cancer. Our results showed that among 478 patients, mesothelin and CA125 were co-expressed in 48 (10 %), mesothelin only in 75 (16 %), CA125 only in 217 (45 %), and neither in 234 (49 %). A high correlation was observed between the expression of mesothelin and CA125 (P =0.0004). The co-expression of mesothelin and CA125 correlated with poor patient relapse-free survival (RFS) (P = 0.0001) and was identified as an independent predictor of RFS by Cox's multivariate analysis. In conclusion, this is the first to report the prognostic significance of the co-expression of mesothelin and CA125 in breast cancer. The co-expression of mesothelin and CA125 may be clinically useful for prognostication after surgical therapy in patients with breast cancer.

Blood pressure levels and bleeding events during antithrombotic therapy: the Bleeding with Antithrombotic Therapy (BAT) Study.

BACKGROUND AND PURPOSE: A prospective, multicenter, observational cohort study was conducted to clarify the association between major bleeding events and blood pressure (BP) levels during follow-up before development of bleeding events in antithrombotic users. METHODS: A total of 4009 patients taking oral antithrombotic agents for cardiovascular or cerebrovascular diseases (2728 men, 69+/-10 years old) were followed. Changes in systolic and diastolic BPs between entry and the last clinic visit before intracranial hemorrhage (ICH) or extracranial hemorrhage were assessed. RESULTS: Over a median follow-up of 19 months, ICH developed in 31 patients and extracranial hemorrhage developed in 77. Entry BP levels were similar among patients with ICH, those with extracranial hemorrhage, and those without hemorrhagic events. Both systolic BP and diastolic BP were relatively high during follow-up as compared with the levels at entry in patients with ICH, whereas they showed plateaus in patients with extracranial hemorrhage and patients without hemorrhagic events. Average systolic BP levels between 1 and 6 months (hazard ratio, 1.45; 95% CI, 1.08 to 1.92 per 10-mm Hg increase) and between 7 and 12 months (hazard ratio, 1.47; 95% CI, 1.05 to 2.01) as well as average diastolic BP levels between 7 and 12 months (hazard ratio, 2.05; 95% CI, 1.15 to 3.62) were independently associated with development of ICH after adjustment for established ICH predictors. The optimal cutoff BP level to predict impending risk of ICH was >or=130/81 mm Hg using receiver operating characteristic curve analysis. CONCLUSIONS: An increase in BP levels during antithrombotic medication was positively associated with development of ICH, suggesting the importance of adequate BP control for avoiding ICH. BP levels did not appear to be associated with extracranial hemorrhage.

Determination of metallization with energy-dispersive X-ray fluorescent spectrometry in experimental electric injury.

We investigated the application of energy-dispersive X-ray fluorescent spectrometry (EDX) analysis to the detection of aluminum (Al), tin (Sn) and zinc (Zn) as the electric conductor in experimental electrical injury. Experimental electrical injury was caused by exposure to alternating current at 100 V for 10 s. The peaks of Al, Sn, and Zn were detected by EDX in formalin-fixed skin samples of each current exposure group. Histological examination revealed blister formation in all samples of each current exposure group. EDX analysis technique can be applied to detect Al, Sn, and Zn as the electric conductor, and is useful in the diagnosis of electrocution.

Significance of mesothelin expression in preoperative endoscopic biopsy specimens for colorectal cancer prognosis.

Mesothelin (MSLN) is a cell surface glycoprotein that is normally expressed in the mesothelial cells but highly expressed in several malignant tumors, where the high expression is generally associated with poor prognosis. In this work, 512 patients with stage III colorectal cancer (CRC) were examined to ascertain the prognostic value of MSLN expression in preoperative endoscopic biopsy specimens. MSLN expression was evaluated by immunohistochemical staining. The tumor cells were MSLN-positive in 61 of the 512 patients (11.9%). MSLN expression was associated with a shorter disease-specific survival (DSS) period (5-year DSS = 68.7%, P = 0.0008). Besides, by multivariate analysis, MSLN expression was identified to be a marker of poor prognosis by multivariate analysis (P = 0.0033, hazard ratio (HR) = 2.31) as well as macroscopic type (P = 0.047, HR = 1.82) among the factors that can be evaluated preoperatively. MSLN-positive patients had a significantly poorer prognosis regardless of adjuvant chemotherapy administration (P = 0.0081 and P = 0.0018 for surgery alone and chemotherapy, respectively). MSLN-positive patients in the adjuvant chemotherapy group exhibited a significantly lower risk of recurrence when compared with those in the surgery alone group (P = 0.0090). In conclusion, high MSLN expression observed in preoperative endoscopic biopsy specimens of stage III CRC was an independent poor prognostic factor. Preoperative evaluation of MSLN by immunohistochemical staining might be applied to select individuals for intensive preoperative chemotherapy among the stage III CRC patients.