Lymph node metastasis detection using artificial intelligence in T1 colorectal cancer: A comprehensive systematic review.

We systematically reviewed the application of artificial intelligence (AI) in predicting lymph node metastasis (LNM) in T1 colorectal cancer (CRC). Thirteen studies with 8417 patients were included. AI demonstrated high potential in predicting LNM with sensitivity, specificity, and AUC ranging from 0.561 to 1.0, 0.45 to 1.0, and 0.717 to 1.0, respectively, reducing unnecessary surgeries by approximately 70%.

The HHEX-ABI2/SLC17A9 axis induces cancer stem cell-like properties and tumorigenesis in HCC.

Accumulating evidence indicated that HHEX participated in the initiation and development of several cancers, but the potential roles and mechanisms of HHEX in hepatocellular carcinoma (HCC) were largely unclear. Cancer stem cells (CSCs) are responsible for cancer progression owing to their stemness characteristics. We reported that HHEX was a novel CSCs target for HCC. We found that HHEX was overexpressed in HCC tissues and high expression of HHEX was associated with poor survival. Subsequently, we found that HHEX promoted HCC cell proliferation, migration, and invasion. Moreover, bioinformatics analysis and experiments verified that HHEX promoted stem cell-like properties in HCC. Mechanistically, ABI2 serving as a co-activator of transcriptional factor HHEX upregulated SLC17A9 to promote HCC cancer stem cell-like properties and tumorigenesis. Collectively, the HHEX-mediated ABI2/SLC17A9 axis contributes to HCC growth and metastasis by maintaining the CSC population, suggesting that HHEX serves as a promising therapeutic target for HCC treatment.

Comparing surgical and endoscopic resection approaches for colorectal neuroendocrine tumors within the diameter range of 10-20mm: an inverse probability weighting analysis based on the SEER database.

Background: Currently, the primary treatment modalities for colorectal neuroendocrine tumors (CRNET) with a diameter between 10mm and 20mm are surgical resection (SR) and endoscopic resection (ER). However, it remains unclear which surgical approach yields the greatest survival benefit for patients. Methods: This study included data from patients diagnosed with CRNET with tumor diameters ranging from 10mm to 20mm between the years 2004 and 2019, obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized into ER and SR groups based on the respective surgical approaches. Inverse probability weighting (IPTW) was employed to mitigate selection bias. Kaplan-Meier analysis and log-rank tests were utilized to estimate overall survival (OS) and cancer-specific survival (CSS). Cox regression analysis (univariate and multivariate) was performed to evaluate potential factors influencing survival. Results: A total of 292 CRNET patients were included in this study (ER group: 108 individuals, SR group: 184 individuals). Prior to IPTW adjustment, Kaplan-Meier analysis and Cox proportional hazard regression analysis demonstrated that the OS and CSS of the SR group were inferior to those of the ER group. However, after IPTW adjustment, no statistically significant differences in prognosis were observed between the two groups. Subgroup analyses revealed that patients with muscular invasion, positive lymph nodes, or distant metastasis derived greater survival benefits from SR. Significant differences in OS and CSS between the two groups were also observed across different age groups. Conclusion: For patients with mucosal-limited lesions and without local lymph node or distant metastasis, ER is the preferred surgical approach. However, for patients with muscular invasion or positive lymph nodes/distant metastasis, SR offers a better prognosis. The choice of surgical approach should be based on the specific clinical characteristics of patients within different subgroups.

The dawn of a new Era: mRNA vaccines in colorectal cancer immunotherapy.

Colorectal cancer (CRC) is a typical cancer that accounts for 10% of all new cancer cases annually and nearly 10% of all cancer deaths. Despite significant progress in current classical interventions for CRC, these traditional strategies could be invasive and with numerous adverse effects. The poor prognosis of CRC patients highlights the evident and pressing need for more efficient and targeted treatment. Novel strategies regarding mRNA vaccines for anti-tumor therapy have also been well-developed since the successful application for the prevention of COVID-19. mRNA vaccine technology won the 2023 Nobel Prize in Physiology or Medicine, signaling a new direction in human anti-cancer treatment: mRNA medicine. As a promising new immunotherapy in CRC and other multiple cancer treatments, the mRNA vaccine has higher specificity, better efficacy, and fewer side effects than traditional strategies. The present review outlines the basics of mRNA vaccines and their advantages over other vaccines and informs an available strategy for developing efficient mRNA vaccines for CRC precise treatment. In the future, more exploration of mRNA vaccines for CRC shall be attached, fostering innovation to address existing limitations.

IRF4 induces M1 macrophage polarization and aggravates ulcerative colitis progression by the Bcl6-dependent STAT3 pathway.

Ulcerative colitis (UC) is an idiopathic chronic intestinal inflammation. An increasing body of evidence shows that macrophages play an important role in the pathogenesis of UC. Interferon regulatory factor 4 (IRF4) is crucial for the development of autoimmune diseases via regulating immune cells. This research was designed to explore the function of IRF4 in UC and its association with macrophage polarization. The in vitro model of UC was established by stimulating colonic epithelial cells with tumor necrosis factor α (TNF-α). A mouse model of UC was constructed by injecting C57BL/6 mice with dextran sulfate sodium salt. Flow cytometry was used to assess percentage of CD11b+ CD86+ and CD11b+ CD206+ cells in bone marrow macrophages. Occult blood tests were used to detect hematochezia. Hematoxylin and eosin staining assay was used to assess colon pathological changes. Enzyme-linked immunosorbent assay (ELISA) was used to detect concentrations of inflammatory cytokines. The interaction of IRF4 and B-cell lymphoma 6 (Bcl6) was confirmed using GST pull-down and coimmunoprecipitation assays. Our findings revealed that IRF4 promoted cell apoptosis and stimulated M1 macrophage polarization in vitro. Furthermore, IRF4 aggravated symptoms of the mouse model of UC and aggravated M1 macrophage polarization in vivo. IRF4 negatively regulated Bcl6 expression. Downregulation of Bcl6 promoted apoptosis and M1 macrophage polarization in the presence of IRF4 in vitro and in vivo. Moreover, Bcl6 positively mediated the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. In conclusion, IRF4 aggravated UC progression through promoting M1 macrophage polarization via Bcl6/JAK2/STAT3 pathway. These findings suggested that IRF4 might be a good target to competitively inhibit or to treat with UC.

Unraveling a novel hippo-associated immunological prognostic signature: The contribution of SERPINE1 in facilitating colorectal cancer progression via the notch signaling pathway.

BACKGROUND: Accumulating evidence demonstrated that Hippo signaling pathway is implicated in tumor initiation and progression. However, there have been limited studies on establishing signatures utilizing genes related to the Hippo pathway to evaluate prognosis and clinical efficacy in colorectal cancer (CRC) patients. METHODS: Hippo pathway-associated genes with prognostic significance were identified in the TCGA database. Subsequently, a prognostic signature associated with the Hippo pathway was constructed using Cox and LASSO regression analyses. Survival analysis, ROC analysis, and stratified analyses were conducted to appraise the performance effect of our prognostic model. We also explored the relationship between the risk score and tumor immune microenvironment. Furthermore, GO analyses and GSEA were performed for SERPINE1. Additional experiments were conducted to illuminate the underlying function and possible mechanism of SERPINE1 in CRC cell proliferation and migration. RESULTS: We identified 58 differentially expressed genes associated with Hippo pathway that have prognostic significance in CRC. Among them, five genes (PPP2CB, SERPINE1, WNT5A, TCF7L1, and LEF1) were selected to establish a prognostic signature for CRC. Multivariate analysis demonstrated that this signature exhibited excellent diagnostic and prognostic performance, providing maximum benefits for CRC patients. In accordance with the prognostic signatures, the cases were divided into low-risk and high-risk groups. Remarkably, the high-risk group displayed lower immune scores, reduced immune cell infiltration, and decreased expression of immune checkpoints. Low-risk group could more possibly benefit from conventional chemotherapeutic and targeted therapies. CRC exhibited significantly elevated expression of SERPINE1, which was linked to worst overall survival. Moreover, inhibition of SERPINE1 suppressed proliferation, invasion, and migration of CRC cells via Notch pathway. CONCLUSIONS: To sum up, we established a novel immunological prognostic signature utilizing genes associated with the Hippo pathway. This signature offers accurate prognostic prediction and can guide individualized therapy for patients with CRC.

Exosome as a crucial communicator between tumor microenvironment and gastric cancer (Review).

Gastric cancer is one of the most common malignancies and has relatively high morbidity and mortality rates. Exosomes are nanoscale extracellular vesicles that originate from a diverse array of cells and may be found throughout various bodily fluids. These vesicles are endogenous nanocarriers in their natural state with the unique ability to transport lipids, proteins, DNA and RNA. Exosomes contain DNA, RNA, proteins, lipids and other bioactive components that have crucial roles in the transmission of information and regulation of cell activities in gastric cancer. This paper begins with an exploration of the composition, formation and release mechanisms of exosomes. Subsequently, the role of exosomes in the tumor microenvironment is reviewed in terms of the immune cell population, nonimmune cell population and other factors. Finally, the current status and challenges of exosome­based research on the progression, diagnosis and therapeutic methods of gastric cancer are summarized. This holistic review offers insight that may guide future research directions for exosomes and potentially pave the way for novel therapeutic interventions in the management of gastric cancer.

N6-methyladenosine methylation analysis of long noncoding RNAs and mRNAs in 5-FU-resistant colon cancer cells.

N6 methyladenosine (m6A), methylation at the sixth N atom of adenosine, is the most common and abundant modification in mammalian mRNAs and non-coding RNAs. Increasing evidence shows that the alteration of m6A modification level could regulate tumour proliferation, metastasis, self-renewal, and immune infiltration by regulating the related expression of tumour genes. However, the role of m6A modification in colorectal cancer (CRC) drug resistance is unclear. Here, MeRIP-seq and RNA-seq techniques were utilized to obtain mRNA, lncRNA expression, and their methylation profiles in 5-Fluorouracil (5-FU)-resistant colon cancer HCT-15 cells and control cells. In addition, we performed detailed bioinformatics analysis as well as in vitro experiments of lncRNA to explore the function of lncRNA with differential m6A in CRC progression and drug resistance. In this study, we obtained the m6A methylomic landscape of CRC cells and resistance group cells by MeRIP-seq and RNA-seq. We identified 3698 differential m6A peaks, of which 2224 were hypermethylated, and 1474 were hypomethylated. Among the lncRNAs, 60 were hypermethylated, and 38 were hypomethylated. GO and KEGG analysis annotations showed significant enrichment of endocytosis and MAPK signalling pathways. Moreover, knockdown of lncRNA ADIRF-AS1 and AL139035.1 promoted CRC proliferation and invasive metastasis in vitro. lncRNA- mRNA network showed that ADIRF-AS1 and AL139035.1 May play a key role in regulating drug resistance formation. We provide the first m6A methylation profile in 5-FU resistance CRC cells and analyse the functions of differential m6A-modified mRNAs and lncRNAs. Our results indicated that differential m6A RNAs were significantly associated with MAPK signalling and endocytosis after induction of 5-FU resistance. Knockdown of LncRNA ADIRF-AS1 and AL139035.1 promotes CRC progression and might be critical in regulating drug resistance formation.

We outline the first m6A methylation profile of mRNA and lncRNA in CRC cells involved in 5-FU resistance.This study sought to identify the critical genes that produced 5-FU resistance by analysing the functions of differentially m6A-modified mRNAs and lncRNAs.

Prediction of distant metastasis and specific survival prediction of small intestine cancer patients with metastasis: A population-based study.

BACKGROUND: Small intestine cancer (SIC) is difficult to diagnose early and presents a poor prognosis due to distant metastasis. This study aimed to develop nomograms for diagnosing and assessing the prognosis of SIC with distant metastasis. METHODS: Patients diagnosed with SIC between 2010 and 2015 were included from the Surveillance, Epidemiology and End Results database. Univariate and multifactor analysis determined independent risk factors for distant metastasis and prognostic factors for overall and cancer-specific survival. We then constructed the corresponding three nomograms and assessed the diagnostic accuracy of the nomograms by net reclassification improvement, receiver operating characteristic curves and calibration curves, assessed the clinical utility by decision curve analysis. RESULTS: The cohort consisted of 6697 patients, of whom 1299 had distant metastasis at diagnosis. Tstage, Nstage, age, tumor size, grade, and histological type were independent risk factors for distant metastasis. Age, histological type, T stage, N stage, grade, tumor size, whether receiving surgery, number of lymph nodes removed, and the presence of bone or lung metastases were predictors of both overall survival and cancer-specific survival. The nomograms showed excellent accuracy in predicting distant metastasis and prognosis. CONCLUSION: Nomograms were developed and validated for SIC patients with distant metastasis, aiding physicians in making rational and personalized clinical decisions.

Target tumor therapy in human gastric cancer cells through the combination of docetaxel-loaded cationic lipid microbubbles and ultrasound-triggered microbubble destruction.

It is well accepted that ultrasound-induced microbubble (USMB) cavitation is a promising method for drug delivery. Ultrasound-targeted destruction of cytotoxic drug-loaded lipid microbubbles (LMs) is used to promote the treatment of cancer. This study aimed to investigate the antitumor effects from a combination of docetaxel-loaded cationic lipid microbubbles (DLLM+) and ultrasound (US)-triggered microbubble destruction (UTMD) on gastric cancer (GC). It was found that the functional dose of DOC in this study was 1 × 10-9 mol/L. We found that DLLM combined with the UTMD group showed greater growth inhibition of the cultured human gastric cancer cells (HGCCs) when compared with the other five groups by arresting the G2/M phase in the cell cycle. However, DLLM+ combined with UTMD showed a higher inhibition rate of tumor growth than DLLM combined with UTMD and that of the RC/CMV-p16 combined with UTMD in vitro and in vivo experiments. DLLM+ combined with UTMD significantly suppressed proliferation and promoted the apoptosis of HGCCs with more cells arrested in the G2/M phase. In addition, DLLM+ combined with UTMD suppressed the proliferation and induced apoptosis by arresting cells in the G2/M phase, which led to a great inhibition of GC progression. Thus, our results indicated that the combination of DLLM+ and UTMD might represent a novel and promising approach to chemotherapy for GC.

The double homeobox a pseudogene 8 accelerates cell proliferation, migration, and invasion in colon cancer.

Double homeobox A pseudogene 8 (DUXAP8) is a known tumor promoter in several malignancies. Nonetheless, its function in colon cancer (CC) is indefinite. Herein, we explored the significance of DUXAP8 and its underlying mechanism in CC. Our data indicated that DUXAP8 was upregulated in CC, and it was related to advanced stages and lymph node metastases. Based on our Kaplan-Meier survival analysis, elevated DUXAP8 expression resulted in shorter patient overall survival (OS). Conversely, DUXAP8 silencing strongly suppressed cellular proliferation, migration and invasion in vitro. Based on our western blot analysis, DUXAP8 deficiency strongly inhibited the epithelial-mesenchymal transition (EMT) in vitro. Alternately, DUXAP8 overexpression accelerated cellular proliferation migration and invasion in CC. Finally, silencing DUXAP8 prevented tumorigenesis in a mouse xenograft model in vivo. Collectively, our results demonstrated that DUXAP8 regulates the occurrence and advancement of CC, and may serve as a regulatory hub for this disease.

RNF2 promotes the progression of colon cancer by regulating ubiquitination and degradation of IRF4.

Ring finger protein 2 (RNF2), as a well-known E3 ligase, has an oncogenic role in various cancers. The role of RNF2 in colon cancer is still unknown. The aim of this work is to determine the biological role of RNF2 in colon cancer. We first examined the expression of RNF2 and interferon regulatory factor 4 (IRF4) in colon cancer patients and colon cancer cell lines (SW480 and HCT116). Compared with normal tumor-adjacent tissues, RNF2 was up-regulated whereas IRF4 was down-regulated in the colon cancer tissues. RNF2 was also up-regulated in colon cancer cells with respect to human fetal colon epithelial cells. RNF2 overexpression enhanced the ability of proliferation, migration and invasion of SW480 cells, whereas RNF2 knockdown caused an opposite result in HCT116 cells. Furthermore, a tumor xenograft model was constructed to verify the impact of RNF2 overexpressed-SW480 cells on tumor growth. RNF2 up-regulation elevated Ki-67 proliferation index, accelerated the growth of tumor tissues, and led to severe colon tissue damage in the tumor xenograft mice. In addition, RNF2 interacted with IRF4, and repressed IRF4 protein expression. IRF4 was a substrate of RNF2, and RNF2 promoted the ubiquitination and degradation of IRF4. RNF2 overexpression increased the ability of proliferation, migration and invasion in SW480 cells by promoting the ubiquitination and degradation of IRF4. In conclusion, this work demonstrated that RNF2 promoted tumor growth in colon cancer by regulating ubiquitination and degradation of IRF4. Thus, RNF2 may be served as a potential therapeutic target for colon cancer.

Laparoscopic versus open radical resection for transverse colon cancer: evidence from multi-center databases.

BACKGROUND: The role of laparoscopic approach is still a controversy for transverse colon cancer. Our investigation aimed to evaluate the perioperative and oncologic outcomes of laparoscopic versus open radical resection for transverse colon cancer based on evidence from multi-center databases. METHODS: 416 patients with transverse colon cancer undergoing radical surgery were analyzed including 181 laparoscopic resections and 235 open resections from January 2004 to May 2017 based on multi-center databases. Perioperative and oncologic outcomes were compared. RESULTS: No statistical differences regarding the baseline characteristics were observed between the two groups except the procedure type. Compared with open approach, laparoscopic approach was associated with statistically longer operation time (209.96 vs. 173.31 min, P = 0.002), significantly shorter time to soft food intake (4.73 vs. 6.01 days, P = 0.034), and shorter postoperative hospitalization (12.05 vs. 14.44 days, P = 0.001). In terms of oncologic outcomes, laparoscopic resection was correlated with statistically more lymph node retrieval (13.52 vs. 15.91, P = 0.002) and similar 5-year overall survival (91.2% vs. 89.1%, P = 0.356) and disease-free survival (89.6% vs. 86.0%, P = 0.873), compared with open resection. CONCLUSIONS: For patients with transverse colon cancer, laparoscopic approach can achieve several short-term advantages without decreasing long-term oncologic survival.

KLHL22 Regulates the EMT and Proliferation in Colorectal Cancer Cells in Part via the Wnt/ß-Catenin Signaling Pathway.

BACKGROUND: Colorectal cancer (CRC) is one of the most common aggressive malignancies. KLHL22 functions as a tumor suppressor, and previous findings have demonstrated that KLHL22 can regulate the development of breast cancer and CRC. However, few studies have investigated the role of KLHL22 in CRC cell epithelial-to-mesenchymal transition (EMT) and proliferation. The current study aimed to detect the role of KLHL22 in CRC cell proliferation and EMT and to elucidate the probable molecular mechanisms through which KLHL22 is involved with these processes. MATERIALS AND METHODS: Transwell invasion, MTT, immunohistochemistry and Western blotting assays were performed to evaluate the migration, invasion and proliferation abilities of CRC cells, and the levels of active molecules involved in the Wnt/ß-catenin signaling pathway were examined through Western blotting analysis. In addition, the in vivo function of KLHL22 was assessed using a tumor xenograft model. RESULTS: KLHL22 expression was weaker in CRC tissues than in nonmalignant tissues and could inhibit cell invasion, migration, and proliferation in vitro. Furthermore, the regulatory effects of KLHL22 on EMT were partially attributed to the Wnt/ß-catenin signaling pathway. The in vivo results also showed that KLHL22 modulated CRC tumorigenesis. CONCLUSION: KLHL22 can regulate the activity of GSK-3ß to influence the level of PI3K, and this regulation promotes EMT inhibition partially through the Wnt/ß-catenin signaling pathway.

Safety and feasibility of laparoscopic liver resection for patients with previous upper abdominal surgery: A systematic review and meta-analysis.

BACKGROUND: Laparoscopic hepatectomy (LH) is technical challenge for patients with previous upper abdominal surgery (UAS), especially for those with previous liver resection. The purpose of this meta-analysis is to assess the safety and feasibility of laparoscopic liver resection for patients with previous UAS, in comparison with primary laparoscopic liver resection which means patients without previous upper abdominal surgery (non-UAS). METHODS: All case-matched articles published from date of inception to 15th April 2018 were identified independently by two reviewers. Perioperative outcomes were analyzed. Data were extracted and calculated by random- or fixed-effect models. In addition, subgroup analysis according to patients with history of liver resection was performed. RESULTS: A total of 8 non-randomized observational articles were included, with 1625 patients (430 patients in UAS group and 1195 in non-UAS group). The results showed that there was no significant difference between the two groups in perioperative outcomes. In the subgroup analysis of patients with a history of liver resection, however, LH for patients with previous liver resection had longer operative time comparing with patients without previous liver resection (WMD = 33.03, 95% CI 3.16 to 62.90, P = 0.030); other perioperative outcomes were similar between UAS and non-UAS groups. CONCLUSION: LH is feasible and safe for selected patients with previous UAS comparing with that of primary resection, although LH has longer operative time for patients with previous liver resection.

Systematic review and meta-analysis of laparoscopic versus open repeat hepatectomy for recurrent liver cancer.

BACKGROUND: Repeat hepatectomy plays a key role in recurrent hepatic tumors. However, it is still unknown whether laparoscopic hepatectomy is suitable for recurrent liver cancers. The aim of this meta-analysis is to evaluate the efficacy and feasibility of laparoscopic repeat hepatectomy (LRH) compared with open repeat hepatectomy (ORH). METHODS: Several databases, including Web of Science, PubMed, The Cochrane Library and Ovid, were retrieved from date of inception to 31st March 2018. All articles comparing LRH and ORH were identified. Tumor characteristics and perioperative outcomes including resection type, operation time, blood loss, transfusion, complications and hospital stay were evaluated. Data were extracted and calculated using random- or fixed-effect models. RESULTS: A total of seven non-randomized observational clinical articles including 443 patients were analyzed. LRH was associated with significantly lower blood loss (WMD = -389.09, 95% CI -628.34 to -149.84, P = 0.001), transfusion (OR 0.16, 95% CI 0.03-0.74, P = 0.019) as well as limited hospital stay (WMD = -4.00, 95% CI -6.58 to -1.42, P = 0.002). No statistical difference was found in the field of tumor characteristics and other perioperative outcomes. In the sensitivity analysis of case-match studies, LRH was associated with significant limited hospital stay, but with significant longer operation time. There were 8 (1.8%, range 0-13.3%) cases of conversion in LRH group. CONCLUSIONS: Based on the results of these limited data, LRH is as feasible and efficient as ORH by expert surgeons in selected patients, whose cancer is resectable at the time of surgery and who have Child-Pugh A or B cirrhosis.

Laparoscopic segmental resection of the rectum for upper rectal intussusception caused by a giant rectal lipoma: A case report.

RATIONALE: Colonic lipomas are rare benign tumours, usually without any symptoms, and most occur in the caecum and ascending colon. We describe a patient with upper rectal intussusception caused by a giant rectal lipoma; no similar report of this type of case has been published. PATIENT CONCERNS: We report the case of a patient who suffered from repeated bloody stools. A wide pedicle polyp (size, 6.5 × 4.5 × 3.5 cm) was detected at the 15th centimetre of the anal canal via an electronic colonoscope. At the initial part of the rectum, intussusception caused by a 6.5-cm fat-density mass was observed via abdominal contrast-enhanced computed tomography. DIAGNOSIS: Upper rectal intussusception caused by a giant rectal lipoma. INTERVENTIONS: Due to the large size of the polyp, an endoscopic polypectomy could not be performed. We performed laparoscopic segmental resection of the rectum (with preservation of the left colic artery [LCA]). OUTCOMES: The patient was discharged on the 7th postoperative day without any complications, was monitored on a regular basis at our outpatient department and was free of symptoms at a 3-month follow-up visit. LESSONS: Laparoscopic segmental resection of the rectum with LCA preservation is safe and feasible for the treatment of upper rectal intussusception caused by a giant rectal lipoma.

CDK8 regulates the angiogenesis of pancreatic cancer cells in part via the CDK8-ß-catenin-KLF2 signal axis.

BACKGROUND: CDK8 is associated with the transcriptional Mediator complex and has been shown to regulate several transcription factors implicated in cancer. As a pancreatic cancer oncogene, the role of CDK8 in cancer angiogenesis remains unclear. Here, we investigated the contribution of CDK8 in pancreatic cancer angiogenesis and examined the underlying molecular mechanisms. METHODS: CDK8 expression was evaluated via immunohistochemistry, western blotting, and qRT-PCR in relation to the clinicopathological characteristics of pancreatic cancer patients. The effects of silencing or overexpressing CDK8 on cancer angiogenesis were assessed in vitro by western blotting assays in pancreatic cancer cell lines and in vivo with nude mice xenograft models. RESULTS: Compared with adjacent normal tissues, pancreatic cancer tissues showed upregulation of CDK8 expression, which was inversely correlated with T grade, liver metastasis, size, lymph node metastasis and poor survival. CDK8 overexpression promoted angiogenesis in pancreatic cancer via activation of the CDK8-ß-catenin-KLF2 signaling axis, as demonstrated by the upregulation and downregulation of signals representing the rate-limiting steps in angiogenesis. Silencing CDK8 inhibited angiogenesis in pancreatic cancer in vitro. Additionally, these results were confirmed in nude mice xenograft models in vivo. CONCLUSIONS: CDK8 promotes angiogenesis in pancreatic cancer via activation of the CDK8-ß-catenin-KLF2 signaling axis, thus providing valid targets for the treatment of pancreatic cancer.