Deletion of Mettl3 in mesenchymal stem cells promotes acute myeloid leukemia resistance to chemotherapy.

Acute myeloid leukemia (AML) cell survival and chemoresistance are influenced by the existence of bone marrow mesenchymal stem cells (BMMSCs); however, the pathways by which BMMSCs contribute to these processes remain unclear. We earlier revealed that methyltransferase-like 3 (METTL3) expression is significantly reduced in AML BMMSCs and that METTL3 mediates BMMSC adipogenesis to promote chemoresistance in human AML cell lines in vitro. In this investigation, we evaluated the METTL3 function in vivo. Mice exhibiting a conditional removal of Mettl3 in BMMSCs were developed by mating Prrx1-CreERT2;Mettl3fl/+ mice with Mettl3fl/fl mice using the CRISPR-Cas9 system. The Mettl3 deletion increased bone marrow adiposity, enhanced disease progression in the transplantation-induced MLL-AF9 AML mouse model, and chemoresistance to cytarabine. The removal of Mettl3 in BMMSCs resulted in a significant increase in BMMSC adipogenesis. This effect was attributed to the downregulation of AKT1 expression, an AKT serine/threonine kinase 1, in an m6A-dependent manner. The development of chemoresistance in AML is linked to the promoted adipogenesis of BMMSCs. We conclude that METTL3 expression in BMMSCs has a critical function in limiting AML progression and chemoresistance, providing a basis for the progression of therapeutic approaches for AML.

Role of NAT10-mediated ac4C-modified HSP90AA1 RNA acetylation in ER stress-mediated metastasis and lenvatinib resistance in hepatocellular carcinoma.

Emerging evidence showed that epigenetic regulation plays important role in the pathogenesis of HCC. N4-acetocytidine (ac4C) was an acetylation chemical modification of mRNA, and NAT10 is reported to regulate ac4C modification and enhance endoplasmic reticulum stress (ERS) in tumor metastasis. Here, we report a novel mechanism by which NAT10-mediated mRNA ac4C-modified HSP90AA1 regulates metastasis and tumor resistance in ERS of HCC. Immunohistochemical, bioinformatics analyses, and in vitro and in vivo experiments, e.g., acRIP-Seq, RNA-Seq, and double luciferase reporter experiment, were employed to investigate the effect of NAT10 on metastasis and drug resistance in HCC. The increased expression of NAT10 was associated with HCC risk and poor prognosis. Cell and animal experiments showed that NAT10 enhanced the metastasis ability and apoptosis resistance of HCC cells in ERS and ERS state. NAT10 could upregulate the modification level of HSP90AA1 mRNA ac4C, maintain the stability of HSP90AA1, and upregulate the expression of HSP90AA1, which further promotes the metastasis of ERS hepatoma cells and the resistance to apoptosis of Lenvatinib. This study proposes a novel mechanism by which NAT10-mediated mRNA ac4C modification regulates tumor metastasis. In addition, we demonstrated the regulatory effect of NAT10-HSP90AA1 on metastasis and drug resistance of ERS in HCC cells.

The influence of meteorological factors and total malignant tumor health risk in Wuhu city in the context of climate change.

With the increasing severity of the malignant tumors situation worldwide, the impacts of climate on them are receiving increasing attention. In this study, for the first time, all-malignant tumors were used as the dependent variable and absolute humidity (AH) was innovatively introduced into the independent variable to investigate the relationship between all-malignant tumors and meteorological factors. A total of 42,188 cases of malignant tumor deaths and meteorological factors in Wuhu City were collected over a 7-year (2014-2020) period. The analysis method combines distributed lagged nonlinear modeling (DLNM) as well as generalized additive modeling (GAM), with prior pre-analysis using structural equation modeling (SEM). The results showed that AH, temperature mean (T mean) and diurnal temperature range (DTR) all increased the malignant tumors mortality risk. Exposure to low and exceedingly low AH increases the malignant tumors mortality risk with maximum RR values of 1.008 (95% CI: 1.001, 1.015, lag 3) and 1.016 (95% CI: 1.001, 1.032, lag 1), respectively. In addition, low and exceedingly low T mean exposures also increased the risk of malignant tumors mortality, the maximum RR was 1.020 (95% CI: 1.006, 1.034) for low T mean and 1.035 (95% CI: 1.014, 1.058) for exceedingly low T mean. As for DTR, all four levels (exceedingly low, low, high, exceedingly high, from low to high) of exposure increased the risk of death from malignant tumors, from exceedingly low to exceedingly high maximum RR values of 1.018 (95% CI: 1.004, 1.032), 1.011 (95% CI: 1.005, 1.017), 1.006 (95% CI: 1.001, 1.012) and 1.019 (95% CI: 1.007, 1.031), respectively. The results of the stratified analysis suggested that female appear to be more sensitive to humidity, while male require additional attention to reduce exposure to high level of DTR.

Clinicopathological and prognostic significance of the long non-coding RNA HOTAIR high expression in head and neck squamous cell carcinoma: a systematic review and meta-analysis.

Background: Long non-coding RNAs (lncRNAs) have been demonstrated to possess critical biological functions that regulate occurrence and progression of tumors. The HOX transcript antisense intergenic RNA (HOTAIR) is one of the most studied lncRNAs. This study was designed to investigate the association of HOTAIR expressions with clinicopathologic features and prognosis in head and neck squamous cell carcinoma (HNSCC). Methods: The PubMed, Web of Science, Embase, Cochrane Library and SCOPUS databases were searched. The studies published before September 10, 2021 were screened. Two authors independently screened the literature and extracted data based on inclusion and exclusion criteria. Meta-analysis, bias assessment, sensitivity analysis and subgroup analysis were performed to improve accuracy and reliability. Results: Seven studies comprising 546 patients were analysed to clarify the relationship between clinicopathologic features and HOTAIR expression, and six studies with 856 patients were applied to evaluate the effects of HOTAIR expressions on the prognosis. After removing those outliers through Galbraith plots and/or sensitivity analysis, the pooled results showed high HOTAIR expressions were associated with high T stage [odds ratio (OR) =2.32, 95% confidence interval (CI): 1.38-3.89, P=0.001], lymphnode metastasis (OR =2.71, 95% CI: 1.57-4.67, P=0.0003), high TNM stage (OR =3.92, 95% CI: 2.28-6.72, P<0.00001), poor histological grade (OR =2.21, 95% CI: 1.02-4.83, P=0.046), poor overall survival (OS) [hazard ratio (HR) =1.74, 95% CI: 1.19-2.56, P=0.005] and poor disease-free survival (DFS) (HR =1.64, 95% CI: 1.09-2.47, P=0.02). Subgroup analyses of T stage, lymphnode metastasis and histological grade identified possible heterogeneity sources, respectively ethnicity, cut-off, and detection methods. Conclusions: These findings suggest HOTAIR might serve as an excellent prognostic biomarker and predictor of clinicopathologic features in HNSCC.

ARHGEF2/EDN1 pathway participates in ER stress-related drug resistance of hepatocellular carcinoma by promoting angiogenesis and malignant proliferation.

Endoplasmic reticulum (ER) stress is widely involved in the drug resistance of hepatocellular carcinoma (HCC), but the mechanism of ER stress-induced drug resistance involves multiple signaling pathways that cannot be fully explained. Exploring genes associated with ER stress could yield a novel therapeutic target for ER stress-induced drug resistance. By analyzing RNA-sequencing, ATAC-sequencing, and Chip-sequencing data of Tunicamycin (TM)-treated or untreated HCC cells, we found that Rho guanine nucleotide exchange factor 2 (ARHGEF2) is upregulated in HCC cells with ER stress. ARHGEF2 plays an active role in tumor malignant progression. Notwithstanding, no research has been done on the link between ER stress and ARHGEF2. The function of ARHGEF2 as a novel downstream effector of ER stress in the angiogenesis and treatment resistance of HCC was revealed in this work. ARHGEF2 overexpression was linked to malignant development and a poor prognosis in HCC. ER stress stimulates the expression of ARHGEF2 through upregulation of ZNF263. Elevated ARHGEF2 accelerates HCC angiogenesis via the EDN1 pathway, enhances HCC cell proliferation and tumor growth both in vitro and in vivo, and contributes to ER stress-related treatment resistance. HCC cell growth was more inhibited when ARHGEF2 knockdown was paired with targeted medicines. Collectively, we uncovered a previously hidden mechanism where ARHGEF2/EDN1 pathway promotes angiogenesis and participates in ER stress-related drug resistance in HCC.

The increased risk of atrial fibrillation in inflammatory arthritis: a systematic review and meta-analysis of cohort studies.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia contributing to stroke and sudden cardiac death. Numbers of studies indicated that patients with inflammatory arthritis have an increased risk of AF. The present study aims to assess the risk of AF in inflammatory arthritis patients. METHODS: We systematically searched cohort studies regarding the risk of AF in patients with rheumatoid arthritis, or spondyloarthritis through PubMed, Web of Science, Cochrane Library, Clinical Trials Registry, and China National Knowledge from inception to August 1, 2019. Meta-analysis was performed using fixed effect model, estimating both crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup analysis and meta-regression based on geographic characteristics, comorbidities, and medication use were conducted to explore the source of heterogeneity. RESULTS: Literature search identified 388 potentially relevant studies, and five studies containing seven cohorts of rheumatoid arthritis or spondyloarthritis were included in the meta-analysis. The AF risk of inflammatory arthritis patients was significantly increased compared with health controls (HR = 1.42, 95% CI: 1.36 to 1.49, Z = 14.17, P < .001), and the pooled HR of studies adjusted factor, like demographic characteristics, medications use, and comorbidities, was 1.37 (95% CI: 1.29 to 1.46; Z = 9.82, P < .001). CONCLUSION: Patients with inflammatory arthritis have increased risk of AF, probably due to the underlying chronic inflammation. Although various confounders have been adjusted like medications use and comorbidities, the risk of AF is still significantly increased in inflammatory arthritis patients. ABBREVIATIONS: AF: Atrial fibrillation; AS: Ankylosing spondylitis; CI: Confidence interval; HR: Hazard ratio; NOS: Newcastle-Ottawa scale; NSAIDs: Non-steroid anti-inflammatory drugs; PsA: Psoriatic arthritis; RA: Rheumatoid arthritis; SpA: Spondyloarthritis; TNFi: Tumor necrosis factors inhibitor; uSpA: Undifferentiated spondyloarthritis.

Bone marrow microenvironment drives AML cell OXPHOS addiction and AMPK inhibition to resist chemotherapy.

The stromal niche plays a pivotal role in AML chemoresistance and energy metabolism reprogramming is a hallmark of a tumor. 5'-Adenosine monophosphate-activated protein kinase (AMPK) is an important energy sensor suppressing mammalian target of rapamycin complex 1 (mTORC1) activity. However, the role of AMPK-mTORC1 pathway on connecting AML cell energy metabolism reprogramming and chemoresistance induced by the bone marrow microenvironment (BMM) is not defined. Here, with a co-culture system that simulates the interaction between BMM and AML cells, it is shown that stromal contact led to a decreased sensitivity to chemotherapy accompanied by an increase of oxidative phosphorylation (OXPHOS) activity and mitochondrial ATP synthesis in AML cells. The increased OXPHOS activity and excessive ATP production promoted chemoresistance of AML cells through inhibiting AMPK activity and in turn activating mTORC1 activity. In an in vivo AML mouse model, depletion of AMPK activity with genetic targeting promoted AML progression and reduced their sensitivity to chemotherapeutic drugs. Collectively, AML cells' acquired increased OXPHOS activity as well as AMPK inhibition could be therapeutically exploited in an effort to overcome BMM-mediated chemoresistance.

Association of FOXO3a gene polymorphisms and ankylosing spondylitis susceptibility in Eastern Chinese Han population.

OBJECTIVE: To investigate the association of FOXO3a polymorphisms and ankylosing spondylitis (AS) susceptibility in Eastern Chinese Han population. METHODS: FOXO3a polymorphisms rs12206094, rs12212067, rs2253310, rs3800232, and rs4946933 were genotyped in 650 AS patients and 646 controls by the improved Multiple Ligase Detection Reaction. RESULTS: The distribution of genotype in rs12212067 polymorphism was significantly different between AS patients and controls (P = 0.020), especially in male population (P = 0.009). There was significant difference of the genotype frequency distribution at rs3800232 between patients and controls in male population. The results of binary regression analysis showed that the rs12212067 GG genotype and rs3800232 TT genotype were obviously correlated with elevated AS risk, and the associations were still significant after being adjusted by age and gender (all P < 0.05). Interestingly, rs12212067 and rs3800232 genotypes were associated with disease activity of patients. Additionally, haplotype block rs12212067G- rs3800232T (OR = 1.403, 95%CI = 1.011-1.949) was further shown to confer promoting effect on developing AS. CONCLUSION: Among Eastern Chinese Han population, FOXO3a polymorphism rs12212067 and rs3800232 may contribute to increased risk of developing AS, but well-designed multicenter studies are needed to further confirm these preliminary findings in the future.

METTL3 mediates bone marrow mesenchymal stem cell adipogenesis to promote chemoresistance in acute myeloid leukaemia.

Adipogenesis of bone marrow mesenchymal stem cells (MSCs) promotes chemoresistance of acute myeloid leukaemia (AML) cells. MSCs from AML patients (AML-MSCs) display enhanced adipogenesis compared with bone marrow MSCs from healthy donors. However, the precise molecular mechanism by which adipogenesis of MSCs from AML marrow differs from normal counterparts remains obscure. We found that METTL3 significantly inhibits MSC adipogenesis. Here, we aimed to identify the molecular mechanism linking METTL3 and MSC adipogenesis. Analysis of m6 A epigenetic changes in MSCs determined via RIP-qPCR and MeRIP-qPCR indicated that METTL3 affects AKT protein expression in MSCs by mediating m6 A modification of AKT1-mRNA. Downregulated METTL3 expression in AML-MSCs induced an increase in AKT protein, resulting in enhanced MSC adipogenesis, thereby contributing to chemoresistance in AML cells. Therefore, targeting AKT regulation by mRNA modification in MSC adipogenesis might provide a novel therapeutic strategy to overcome AML chemoresistance.

The peptide encoded by a novel putative lncRNA HBVPTPAP inducing the apoptosis of hepatocellular carcinoma cells by modulating JAK/STAT signaling pathways.

When the hepatitis B virus (HBV) enters target cells, there are complex trans-regulatory mechanisms involved in the interactions between the virus and the target cells. In the present study, a new gene screened from the hepatoblastoma cell line HepG2 using suppression subtractive hybridization, referred to as lncRNA HBVPTPAP, was used to study the trans-regulation of HBV DNA polymerase. According to the structural characteristics of the full-length sequences, it was classified as long non-coding RNA. However, a unique and complete open reading frame (ORF) was still present. Therefore, to further identify the lncRNA HBVPTPAP gene's encoding potential, this study used several online tools to analyze and verify its encoding polypeptide authenticity. On that basis, the effects of the lncRNA HBVPTPAP gene on the biological behaviors of HepG2 cells and its molecular regulatory mechanism were investigated. It was found that the lncRNA HBVPTPAP subcellular was mainly located in the cytoplasm, and possibly activated the downstream JAK/STAT signaling pathway through the interaction between the encoding polypeptide and PILRA intracellular domain. Then, the mitochondrial apoptosis pathway may have been initiated to induce apoptosis. These results provided a basis for further study of the biological functions of the lncRNA HBVPTPAP gene.

Surgery on primary tumor shows survival benefit in selected stage IV colon cancer patients: A real-world study based on SEER database.

Objectives: Most patients with stage IV colon cancer did not have the opportunity for curative surgery, only selected patients could benefit from surgery. This study aimed to determine whether surgery on the primary tumor (SPT) should be performed in patients with stage IV colon cancer and how to select patients for SPT. Methods: This study included 48,933 patients with stage IV colon cancer who were identified in the Surveillance, Epidemiology and End Results (SEER) database between 1998 and 2015. Propensity score matching (PSM) analysis was adopted to balance baseline differences between SPT and non-surgery groups. Kaplan-Meier (K-M) curves were utilized to compare the overall survival (OS). Prognostic nomograms were generated to predict survival based on pre- and post-operative risk factors. Patients were divided into low, middle, and high mortality risk subsets for OS by X-tile analyses based on scores derived from above nomograms. Results: Patients with SPT had a significantly longer OS than those without surgery, regardless of the metastatic sites and diagnostic years. Nomograms, according to the pre- and post-operative risk factors, showed moderate discrimination (all C-indexes above 0.7). Based on X-tile analyses, low mortality risk subset (post-operative score ≤ 22.3, preoperative score ≤ 9.7) recommended for SPT, and high mortality risk was not. Conclusions: SPT led to prolonged survival in stage IV colon cancer. Our nomograms would help to select suitable patients for SPT.

H19 Increases IL-17A/IL-23 Releases via Regulating VDR by Interacting with miR675-5p/miR22-5p in Ankylosing Spondylitis.

Long non-coding RNA (lncRNA) H19 is associated with inflammatory diseases, but the molecular mechanism of H19 in the inflammatory process of ankylosing spondylitis (AS) is unclear. Here, we investigated the role of H19 and its downstream molecules in the inflammation of AS by microarray analysis, qRT-PCR, western blot, and dual-luciferase reporter assay. H19 small interfering RNA (siRNA) (Si-H19) and adenovirus (AD-H19) were used to decrease and increase H19 expression, respectively. 42 annotated lncRNAs were identified, and H19 was overexpressed. H19, vitamin D receptor (VDR), and transforming growth factor ß (TGF-ß) can bind to microRNA22-5p (miR22-5p) and miR675-5p. Si-H19 significantly downregulated miR22-5p and upregulated miR675-5p expression; Si-H19 decreased the protein and mRNA expression of VDR and decreased the cytokine and mRNA levels of interleukin-17A (IL-17A) and IL-23. These results were verified by AD-H19. In addition, miR22-5p and miR675-5p inhibitors increased the protein and mRNA expression of VDR and increased the cytokine and mRNA levels of IL-17A and IL-23. These results were also confirmed by miRNA mimics. Furthermore, H19 directly interfered with miR22-5p and miR675-5p expression, whereas the two miRNAs directly inhibited VDR expression. Overall, the H19-miR22-5p/miR675-5p-VDR-IL-17A/IL-23 signaling pathways have important roles in the pathogenesis of AS.

Comparative Efficacy and Safety of Common Therapies in Keloids and Hypertrophic Scars: A Systematic Review and Meta-analysis.

OBJECTIVES: At present, there are many therapies for treating keloids and hypertrophic scars, but there is still a lack of treatments that are relatively balanced in efficacy and safety. The study aims to evaluate comprehensively efficacy and safety of common therapies in keloids and hypertrophic scars. METHODS: The literature search was conducted up to May 2019. The traditional meta-analysis was performed on 17 therapies. Bayesian network meta-analysis was conducted on the four most common treatments. The outcome indicators were the numbers of patients with good-to-excellent effect, Vancouver Scar Scale (VSS) and adverse events. RESULTS: There was no significant difference in the efficacy of triamcinolone acetonide (TAC) compared with other monotherapies except for silicone gel sheet and neodymium-yttrium-aluminum-garnet in primary indicator. The combination therapies were superior to TAC, and the results were consistent after the pooled analysis (RR = 0.522, 95% CI 0.332-0.823). The level of VSS in TAC group was higher than that in 5-flurouracil (5-FU) and TAC + 5-FU group, but lower than that in verapamil (VER) group. And the patients treated with TAC were less safe than those treated with verapamil (P = 0.013). Surface under cumulative ranking ranked verapamil and TAC + 5-FU as the favorable efficacy therapies in terms of primary indicator and ranked TAC + 5-FU as the best therapy for VSS, while VER was ranked as the worst. CONCLUSION: This meta-analysis showed that TAC + 5-FU may be the most effective therapy, while verapamil may be a better therapeutic strategy for safety. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Elevated circulating IL-17 level is associated with inflammatory arthritis and disease activity: A meta-analysis.

OBJECTIVES: Previous studies found that the interleukin (IL)-17 level was elevated in inflammatory arthritis, but results were inconsistent. This meta-analysis aimed to investigate the association of IL-17 cytokine with osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). METHODS: Relevant studies were searched using databases. Standardized mean difference (SMD) was calculated. Correlation coefficient was utilized to evaluate the relationship between IL-17 and disease activity of AS and RA. Subgroup analysis, sensitivity analysis and meta-regression were applied to explore the sources of heterogeneity. RESULTS: 83 records were enrolled. The IL-17 level was elevated in AS (SMD = 2.348, P < .001), RA (SMD = 1.502, P < .001), PsA (SMD = 1.710, P < .001) and OA (SMD = 1.192, P = .016), and similar results occurred in subgroup analysis. Furthermore, the IL-17 level was positively associated with disease activity of AS and RA. CONCLUSION: Circulating IL-17 level is significantly elevated in inflammatory arthritis and is related to the disease activity of AS and RA, suggesting that it plays an important role in the pathogenesis and progression of inflammatory arthritis (especially in AS and RA).

Associations between VDR gene polymorphisms and colorectal cancer susceptibility: an updated meta-analysis based on 39 case-control studies.

BACKGROUND: Recent studies have reported the associations between vitamin D receptor (VDR) polymorphisms and colorectal cancer (CRC), but the results were not always consistent. This meta-analysis aims to evaluate whether VDR polymorphisms are associated with CRC susceptibility. MATERIALS AND METHODS: Studies on the associations between VDR polymorphisms and CRC were retrieved from the Web of Science, PubMed, the Chinese Biomedical Database (CBM), Chinese National Knowledge Infrastructure (CNKI) and Wanfang (Chinese) databases. The odds ratio (OR) with 95% confidence intervals (CIs) was obtained. RESULTS: Thirty-nine articles met all inclusion criteria and were included in the meta-analysis including 22101 CRC cases and 23696 healthy controls. The 39 articles consisted of five VDR gene polymorphisms including ApaI, FokI, BsmI, TaqI and Cdx2. The results of meta-analysis showed that the FokI polymorphism was on the fringe of statistically significant in the comparisons of F allele vs. f allele in fixed model (OR = 1.029, 95% CI = 0.999-1.059, Praw = 0.057, PFDR = 0.057). Moreover, for the associations between BsmI polymorphism with CRC, We observed significant differences in allele frequencies, the homozygous model and the dominant model between CRC patients and healthy controls (B vs. b: OR = 0.862, 95% CI = 0.761-0.976, Praw = 0.019, PFDR = 0.019; BB vs. bb: OR = 0.786, 95% CI = 0.636-0.972, Praw = 0.026, PFDR = 0.039; BB + Bb vs. bb: OR = 0.934, 95% CI = 0.888-0.982, Praw = 0.008, PFDR = 0.024, respectively). CONCLUSIONS: This meta-analysis suggests that BsmI is associated with CRC risk and FokI might be a risk factor for CRC. However, these associations with CRC need further studied.

Role of IL-6-mediated expression of NS5ATP9 in autophagy of liver cancer cells.

This study aimed to investigate the relationship between interleukin-6 (IL-6) and NS5ATP9 in autophagy of liver cancer cells. Autophagy is one of the important regulators of the replication of hepatitis C virus and the survival of tumors. IL-6 is a multifunctional cytokine that plays an important role in autophagy and development of many kinds of tumors. However, the role of IL-6 in autophagy has not been fully explored. A previous study had shown that a novel gene, NS5ATP9, could modulate autophagy. The present study demonstrated that human IL-6 recombinant protein induced autophagy of HepG2 cells. Conversely, autophagy decreased after IL-6 was silenced or neutralized with monoclonal antibody against human IL-6. In addition, NS5ATP9 was upregulated by IL-6 via nuclear factor-kappaB activation, as detected by Western blot. Further studies indicated that the induction of autophagy by IL-6 could be attenuated by silencing NS5ATP9. Interestingly, the expression of NS5ATP9, in turn, resulted in the upregulation of IL-6. In conclusion, IL-6 could induce autophagy by expressing NS5ATP9, while NS5ATP9 upregulated IL-6 levels in turn, which further induced autophagy.

Expression and clinical significance of Sirt1 in colorectal cancer.

The objective of the present study was to examine the expression of Silent information regulator 1 (Sirt1) in colorectal cancer and peritumoral normal mucosa tissue, and therefore analyze the role and molecular mechanism of Sirt1 in the pathogenesis of colorectal cancer. Colorectal cancer tissue specimens were employed as the experimental group, and adjacent normal mucosa tissues >5 cm from tumor lesions were used as the control group. The expression of Sirt1 was detected by the immunohistochemical streptavidin peroxidase detection method in paraffin-embedded sections, whilst Sirt1 protein expression was examined by western blot analysis in the fresh tissues. Sirt1 protein was primarily expressed in the nuclei of the tumor cells, and positive staining was brownish-yellow in color. The relative expression quantities of Sirt1 in the peritumoral normal rectal mucosa and rectal carcinoma were 1.15 and 2.62, and the differences between the two groups were statistically significant (P<0.05). The expression level of Sirt1 in colorectal carcinoma was significantly associated with the depth of tumor invasion, differentiation and tumor size (P<0.05). Sirt1 expression was also found to be associated with tumor tissue type, lymph node metastasis, Duke's stage and patient age. These characteristics combined may therefore be used as markers for the early diagnosis of colorectal cancer pathogenesis.