Suppression of pancreatic cancer proliferation through TXNIP-mediated inhibition of the MAPK signaling pathway.

Thioredoxin-interacting protein (TXNIP) is a crucial thioredoxin-binding protein that is recognized as a tumor suppressor in diverse malignancies, such as breast cancer, lung cancer, hepatocellular carcinoma, and thyroid cancer. However, the specific role and molecular mechanisms of TXNIP in the pathogenesis and progression of pancreatic cancer cells have not been determined. In this study, we investigate the relationship between TXNIP expression and overall survival prognosis in pancreatic cancer patients. Mechanistic studies are conducted to reveal the role of TXNIP in pancreatic cancer cell proliferation, migration, and regulation during malignancy. Our findings indicate that patients with high TXNIP expression have a more favorable prognosis. In vitro experiments with pancreatic cell lines show that overexpression of TXNIP suppresses the proliferation and migration of pancreatic cancer cells. Furthermore, we find that TXNIP inhibits the activation of the MAPK signaling pathway, thereby decreasing the malignant potential of pancreatic cancer. In conclusion, our study reveals TXNIP as a promising new predictive marker and therapeutic target for pancreatic cancer.

Tissue-resident CXCR4+ macrophage as a poor prognosis signature promotes pancreatic ductal adenocarcinoma progression.

Macrophage is an essential part of the tumor immune microenvironment of pancreatic ductal adenocarcinoma. In our study, we explored the CXCR4+ macrophages subset on its prognosis value, immune profile and distinct function in pancreatic cancer progression. Specimens from 102 postoperative pancreatic patients were analyzed by flow cytometry or immune-fluorescence, and the prognostic value of CXCR4+ macrophages infiltration was further determined by Cox regression. In silico analysis on TCGA, ICGC database and single-cell sequencing of pancreatic ductal adenocarcinoma further validated our findings. We found that high CXCR4+ macrophages infiltration was associated with poor overall survival (P < .01) and disease-free survival (P < .05) as an independent factor. CXCR4+ macrophages exhibited an M2 protumor phenotype with high expression of CD206. The function of CXCR4+ macrophages was further analyzed in the murine orthotopic PDAC model with its tumor promotion effect and inhibition of CD8+ T cells. Mechanistic and RNA-seq analysis showed that CXCR4+ macrophages participated in extracellular matrix remodeling procedures and especially secreted SPARC through CXCR4/PI3K/Akt pathway promoting tumor proliferation and migration. Our study reveals that CXCR4+ macrophages infiltration is an indicator of poor prognosis of PDAC and targeting these cells was potentially crucial in immunotherapy of PDAC.

Novel strategy for oncogenic alteration-induced lipid metabolism reprogramming in pancreatic cancer.

The pathogenesis of pancreatic cancer involves substantial metabolic reprogramming, resulting in abnormal proliferation of tumor cells. This tumorigenic reprogramming is often driven by genetic mutations, such as activating mutations of the KRAS oncogene and inactivating or deletions of the tumor suppressor genes SMAD4, CDKN2A, and TP53, which play a critical role in the initiation and development of pancreatic cancer. As a normal cell gradually develops into a cancer cell, a series of signature characteristics are acquired: activation of signaling pathways that sustain proliferation; an ability to resist growth inhibitory signals and evade apoptosis; and an ability to generate new blood vessels and invade and metastasize. In addition to these features, recent research has revealed that metabolic reprogramming and immune escape are two other novel characteristics of tumor cells. The effect of the interactions between tumor and immune cells on metabolic reprogramming is a key factor determining the antitumor immunotherapy response. Lipid metabolism reprogramming, a feature of many malignancies, not only plays a role in maintaining tumor cell proliferation but also alters the tumor microenvironment by inducing the release of metabolites that in turn affect the metabolism of normal immune cells, ultimately leading to the attenuation of the antitumor immune response and resistance to immunotherapy. Pancreatic cancer has been found to have substantial lipid metabolism reprogramming, but the mechanisms remain elusive. Therefore, this review focuses on the mechanisms regulating lipid metabolism reprogramming in pancreatic cancer cells to provide new therapeutic targets and aid the development of new therapeutic strategies for pancreatic cancer.

TGF-ß1-induced RAP2 regulates invasion in pancreatic cancer.

Pancreatic cancer is highly lethal due to its aggressive invasive properties and capacity for metastatic dissemination. Additional therapeutic targets and effective treatment options for patients with tumours of high invasive capacity are required. Ras-related protein-2a (RAP2) is a member of the GTP-binding proteins. RAP2 has been reported to be widely upregulated in many types of cancers via regulating cytoskeleton reorganization, cell proliferation, migration, and adhesion, as well as inflammation. As a member of the RAS oncogene family, which has been demonstrated to drive pancreatic cancer oncogenesis and many other malignancies, the physiological roles of RAP2 in pancreatic cancer have seldom been discussed. In the present study, we explored the correlation between RAP2 expression and the prediction of overall survival of pancreatic cancer patients. Mechanistic studies were carried out to shed light on the role of RAP2 in pancreatic cancer invasion and how RAP2 is regulated in the invasive process. Our results demonstrated that patients with higher RAP2 expression showed unfavourable prognoses. studies demonstrated that silencing of inhibited the invasion of pancreatic cancer cells. Moreover, our results demonstrated that transforming growth factor-ß1 (TGF-ß1), an inducer of the metastatic potential of pancreatic cancer cells, regulates the expression of RAP2 via the transcription factor c-Myc. In conclusion, the present study uncovered RAP2 as a novel predictive marker and therapeutic target for pancreatic cancer.

Innate Lymphoid Cells: Emerging Players in Pancreatic Disease.

Common pancreatic diseases have caused significant economic and social burdens worldwide. The interstitial microenvironment is involved in and plays a crucial part in the occurrence and progression of pancreatic diseases. Innate lymphoid cells (ILCs), an innate population of immune cells which have only gradually entered our visual field in the last 10 years, play an important role in maintaining tissue homeostasis, regulating metabolism, and participating in regeneration and repair. Recent evidence indicates that ILCs in the pancreas, as well as in other tissues, are also key players in pancreatic disease and health. Herein, we examined the possible functions of different ILC subsets in common pancreatic diseases, including diabetes mellitus, pancreatitis and pancreatic cancer, and discussed the potential practical implications of the relevant findings for future further treatment of these pancreatic diseases.

Indocyanine green real-time-guided laparoscopic duodenum-preserving pancreatic head resection.

Duodenum-preserving pancreatic head resection (DPPHR) is very complicated due to its difficulty to find the lower common bile duct (CBD), and to preserve the blood supply of the duodenum and CBD. Recently, indocyanine green (ICG) has been widely applied for navigation during biliary system and liver surgery. However, the application of ICG-guided laparoscopic DPPHR has not been established. Herein, we report an intraoperative angiography technique using ICG fluorescence imaging to visualise blood flow, tissue perfusion, CBD navigation and bile leakage assessment.

How to Perform Total Laparoscopic Duodenum-Preserving Pancreatic Head Resection Safely and Efficiently with Innovative Techniques.

BACKGROUND: Although rapid progress has been achieved in laparoscopic pancreaticoduodenectomy (PD) over the last decade, laparoscopic duodenum-preserving pancreatic head resection (LDPPHR) remains a challenging surgery that has been rarely reported due to not only requiring complicated pancreaticojejunostomy (PJ) but also ensuring sufficient blood supplies to duodenum and common bile duct (CBD). We completed LDPPHR for 22 patients safely and efficiently with innovative techniques. PATIENTS AND METHODS: Clinical outcomes, including rate of conversion to laparotomy, time of residual pancreatic duct reconstruction, incidence of postoperative complications, and time of hospital stay, were collected for 22 consecutive patients who underwent LDPPHR with innovative techniques as follows: application of indocyanine green (ICG) to visualize and preserve CBD and the vessels supplying the duodenum and CBD, Hong's PJ, and pancreatic duct end-to-end anastomosis (ETEA) for the residual pancreas. RESULTS: All surgeries were performed successfully under laparoscopy except for one case. The duration of ETEA was significantly shorter than PJ (18.2 ± 5.1 min versus 27.5 ± 8.3 min, p < 0.05). There was no significant difference in incidence of postoperative complications between the Hong's PJ and ETEA group. The overall incidence of postoperative pancreatic fistula (POPF) in the Hong's PJ and ETEA group was 23.5% and 20%, respectively, without grade C fistula. All complications were resolved after conservative treatment. CONCLUSIONS: By utilizing intraoperative ICG navigation, LDPPHR is a minimally invasive, safe, and efficient approach for chronic pancreatitis with pancreatic head stones by using pancreatic duct ETEA and benign or low-grade malignant tumors of the pancreatic head by using Hong's PJ.

High GFPT1 expression predicts unfavorable outcomes in patients with resectable pancreatic ductal adenocarcinoma.

BACKGROUND: Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) is the first rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP), which plays a pivotal role in the progression of pancreatic ductal adenocarcinoma (PDAC). Therefore, we investigated the prognostic significance of GFPT1 expression in patients with resectable PDAC. METHODS: We analyzed public datasets to compare GFPT1 expression in tumor tissues and normal/adjacent pancreatic tissues. We measured the relative GFPT1 expression of 134 resected PDAC specimens in our institution, using real-time polymerase chain reaction (PCR). Survival was compared between high and low GFPT1 expression groups using Kaplan-Meier curves and log-rank tests. Multivariate analyses were estimated using Cox regression and logistic regression models. RESULTS: GFPT1 is generally upregulated in PDAC tissues, according to the analysis of public datasets. The data from our institution shows that high GFPT1 expression was correlated with a high rate of lymph node (LN) metastasis (p = 0.038) and was an independent risk factor for LN metastasis (odds ratio (OR) = 3.14, 95% confidence interval (CI) = 1.42 to 6.90, P = 0.005). High GFPT1 expression was significantly associated with poor overall survival (OS; P = 0.019) in patients with resected PDAC. The multivariable-adjusted hazard ratio (HR) for mortality when comparing patients with high and low GFPT1 expression was 2.54 (95% CI = 1.35 to 4.79, P = 0.004). CONCLUSIONS: GFPT1 is generally upregulated in PDAC tissue and is associated with a high risk of LN metastasis and an unfavorable outcome in patients with resectable PDAC, suggesting its crucial role in PDAC progression.

Silencing of LAMC2 Reverses Epithelial-Mesenchymal Transition and Inhibits Angiogenesis in Cholangiocarcinoma via Inactivation of the Epidermal Growth Factor Receptor Signaling Pathway.

Cholangiocarcinoma (CCA) is a malignant cancer that is associated with high mortality rates. The relationship between laminin γ 2 chain gene (LAMC2) and epidermal growth factor receptor (EGFR) has been previously documented in gastric cancer and oral squamous cell carcinoma. This study investigates the role of LAMC2 in epithelial-mesenchymal transition (EMT) and angiogenesis in CCA and explores the underlying mechanism(s). Differentially expressed genes related to CCA were initially screened using a microarray analysis, and the interaction between LAMC2 and the EGFR signaling pathway was identified. To determine the regulatory effects of LAMC2 on CCA progression, LAMC2 was silenced or overexpressed and the EGFR signaling pathway was activated or blocked. Subsequently, the regulation effects of LAMC2 were evaluated on the expression of EMT markers, invasion and migration of CCA cells, as well as microvessel density in nude mice. Microarray analysis demonstrated that highly expressed LAMC2 is linked to CCA development, which involves the EGFR signaling pathway. When LAMC2 expression was increased, the EGFR signaling pathway and EMT were activated in CCA tissues. Silencing of LAMC2 as well as EGFR signaling pathway inhibition led to suppression of EMT, cell invasion, and migration abilities in vitro, as well as angiogenesis in vivo. This study demonstrates that LAMC2 silencing suppresses the activity of the EGFR signaling pathway, thus functioning as a tumor suppressor in CCA.

Methyl-CpG Binding Domain Protein 2 Inhibits the Malignant Characteristic of Lung Adenocarcinoma through the Epigenetic Modulation of 10 to 11 Translocation 1 and miR-200s.

It has been reported that disorders of epigenetic modulation play a critical role in carcinogenesis. Methyl-CpG binding domain protein 2 (MBD2) is known to act as an epigenetic modulator in various types of tumors; however, the role of MBD2 in lung adenocarcinoma (LUAD) remains unclear. Herein, we demonstrated the down-regulation of MBD2 in LUAD compared with adjacent nontumor tissues. The down-regulation of MBD2 in LUAD was correlated with metastasis and poor survival. In addition, MBD2 inhibited tumor metastasis by maintaining the expression of the miR-200s, which suppressed the invasive properties of tumors. Also, MBD2 positively correlated with 5-hydroxymethylcytosine content in the promoter of miR-200s. The conventional view is that MBD2 acts as a transcriptional suppressor. However, the data revealed that MBD2 may act as a transcriptional activator by recruiting 10 to 11 translocation 1 (TET1) and forming a chromatin-remodeling complex. The MBD2-TET1 complex locates to the TET1 promoter and removes the methyl residues in this region, thereby activating TET1 transcription. TET1 also acted as a tumor suppressor in LUAD. Taken together, the data demonstrate the correlation between MBD2, miR-200s, and TET1, and tumor suppressive effect of MBD2 through up-regulation of TET1 and the miR-200s.

Total laparoscopic versus open radical resection for hilar cholangiocarcinoma.

BACKGROUND: Radical resection is the only curative option for patients with hilar cholangiocarcinoma (HCCA) to achieve long-term survival. However, due to the fact that radical resection of HCCA has high technical requirements, the safety and efficacy of laparoscopic resection for HCCA remains controversial. METHOD: From January 2015 to December 2018, 23 cases of HCCA underwent radical resection in our center. Clinical data of those patients were collected and analyzed retrospectively. RESULTS: 14 patients underwent laparoscopic resection and 9 cases received open resection. 2 patients in laparoscopic group were converted to laparotomy. Operation time in laparoscopic group was significantly longer than that in open group (519.4 ± 155.4 min vs 366.7 ± 93.1 min). Estimated blood loss (620.0 ± 681.2 ml vs 821.4 ± 713.8 ml) and incidence of intraoperative blood transfusion (5/9 vs 8/14) did not differ significantly between two groups. Pathological outcomes were comparable between two groups. Length of postoperative hospital stay (23.4 ± 13.4 days vs 17.8 ± 7.1 days), severe postoperative morbidity (3/9 vs 5/14), bile leakage of Grade A or B (5/9 vs 5/14), intra-abdominal bleeding (0/9 vs 1/14), intra-abdominal abscess (1/9 vs 0/14), wound infection (0/9 vs 1/14), pulmonary infection (2/9 vs 0/14), and liver failure (0/9 vs 0/14) did not differ significantly between two groups. One patient in laparoscopic group died (1/14) at 21 postoperative days due to intra-abdominal bleeding, while no 30-day mortality was observed in open group. CONCLUSION: Our results demonstrate that laparoscopic radical resection of HCCA is safe and feasible in experienced hands. Although laparoscopic resection for HCCA, which is still in initial and exploratory stage, fails to show any advantage over open resection in this study, we are optimistic with its wide application in future with the improvement of surgical techniques and experience.

WITHDRAWN: Individualized and pancreatic duct diameter-based strategy for pancreaticoenteric anastomosis during pancreaticoduodenectomy.

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Indocyanine green retention is a potential prognostic indicator after splenectomy and pericardial devascularization for cirrhotic patients.

BACKGROUND: Splenectomy and pericardial devascularization (SPD) is an effective treatment of upper gastrointestinal bleeding and hypersplenism in cirrhotic patients with portal hypertension. Indocyanine green retention at 15 minutes (ICGR15) was reported to offer better sensitivity and specificity than the Child-Pugh classification in hepatectomy, but few reports describe ICGR15 in SPD. The present study was to evaluate the prognostic value of ICGR15 for cirrhotic patients with portal hypertension who underwent SPD. METHODS: From January 2012 to January 2015, 43 patients with portal hypertension and hypersplenism caused by liver cirrhosis were admitted in our center and received SPD. The ICGR15, Child-Pugh classification, model for end-stage liver disease (MELD) score, and perioperative characteristics were analyzed retrospectively. RESULTS: Preoperative liver function assessment revealed that 34 patients were Child-Pugh class A with ICGR15 of 13.6%-43.0% and MELD score of 7-20; 8 patients were class B with ICGR15 of 22.8%-40.7% and MELD score of 7-17; 1 patient was class C with ICGR15 of 39.7% and MELD score of 22. The optimal ICGR15 threshold for liver function compensation was 31.2%, which offered a sensitivity of 68.4% and a specificity of 70.8%. Univariate analysis showed preoperative ICGR15, MELD score, surgical procedure, intraoperative blood loss, and autologous blood transfusion were significantly different between postoperative liver function compensated and decompensated groups. Multivariate regression analysis revealed that ICGR15 was an independent risk factor of postoperative liver function recovery (P=0.020). CONCLUSIONS: ICGR15 has outperformed the Child-Pugh classification for assessing liver function in cirrhotic patients with portal hypertension. ICGR15 may be a suitable prognostic indicator for cirrhotic patients after SPD.

Comparison of two laparoscopic splenectomy plus pericardial devascularization techniques for management of portal hypertension and hypersplenism.

OBJECTIVE: Our research was conducted to analyze the outcomes of two laparoscopic splenectomy plus pericardial devascularization (LSPD) techniques in the management of portal hypertension (PTH) and hypersplenism. METHODS: Between May 2012 and May 2013, 41 patients with PTH and hypersplenism undergoing LSPD were retrospectively analyzed. Of them, 29 patients received LSPD by LigaSure Vessel Sealing System (LVSS) and Endo-GIA universal endoscopic vascular linear staplers (Endo-GIA) (EG Group) and 12 patients received LSPD by LVSS and Hem-o-Lock (HL Group). Operating time, intraoperative blood loss, postoperative course, and hospitalization costs were compared between the two LSPD combination techniques. RESULTS: There were no significant differences in preoperative patient characteristics of the two groups. Significantly less operating time, intraoperative blood loss, and postoperative complications were observed in EG Group. The incidence of portal vein thrombosis was lower in the EG Group (3.4 vs. 8.3%), as well as the incidence of pancreatic fistula (0 vs. 8.3%). Upper gastrointestinal hemorrhage was not observed in either group. Uncontrolled bleeding warranted conversion to open surgery in one case in EG Group (conversion rate 3.4%) and in two cases in HL Group (conversion rate 16.7%). Two patients (16.7%) in HL Group underwent successful emergency exploratory laparotomy due to uncontrolled intraabdominal bleeding postoperatively. No re-operation was needed in EG Group. Two patients experienced liver failure after surgery in each group. Of those, three patients were managed successfully and one patient refused further therapy. While the overall complication rate was significantly lower in EG Group (17.2 vs. 58.3%, P < 0.05), overall hospitalization costs remained significantly higher for EG Group. CONCLUSION: The results suggest that the modified Endo-GIA and LVSS technique is a safe and effective combination approach to LSPD with shorter operative time, less intraoperative blood loss, lower conversion rate to laparotomy, shorter hospital stay, better recovery, and lower postoperative complication rate compared with the Hem-o-Lock and LVSS approach. Higher hospitalization expenses associated with the Endo-GIA and LVSS approach.

Partial hepatectomy for primary hepatic melanoma: a report of two cases and review of the literature.

Malignant melanoma is an extremely aggressive cancer arising from melanocytes, associated with the development of metastases in up to 20% of patients. Although the liver is a frequent metastatic site of malignant melanoma, primary hepatic melanoma (PHM) is rare. The treatment of PHM is controversial, and the prognosis for affected patients remains poor. We present two PHM patients who underwent partial hepatectomy at our institution and review the clinical and pathological data from these cases. Our results suggest that it is difficult to make a preoperative diagnosis of PHM without pathological results. For patients with resectable PHM, surgical resection is a potentially curative treatment.

Cordycepin down-regulates multiple drug resistant (MDR)/HIF-1α through regulating AMPK/mTORC1 signaling in GBC-SD gallbladder cancer cells.

Gallbladder cancer is the most common malignancy of the bile duct, with low 5-year survival rate and poor prognosis. Novel effective treatments are urgently needed for the therapy of this disease. Here, we showed that cordycepin, the bioactive compound in genus Cordyceps, induced growth inhibition and apoptosis in cultured gallbladder cancer cells (Mz-ChA-1, QBC939 and GBC-SD lines). We found that cordycepin inhibited mTOR complex 1 (mTORC1) activation and down-regulated multiple drug resistant (MDR)/hypoxia-inducible factor 1α (HIF-1α) expression through activating of AMP-activated protein kinase (AMPK) signaling in gallbladder cancer GBC-SD cells. Contrarily, AMPKα1-shRNA depletion dramatically inhibited cordycepin-induced molecular changes as well as GBC-SD cell apoptosis. Further, our results showed that co-treatment with a low concentration cordycepin could remarkably enhance the chemosensitivity of GBC-SD cells to gemcitabine and 5-fluorouracil (5-FU), and the mechanism may be attributed to AMPK activation and MDR degradation. In summary, cordycepin induces growth inhibition and apoptosis in gallbladder cancer cells via activating AMPK signaling. Cordycepin could be a promising new drug or chemo-adjuvant for gallbladder cancer.

The GFPT2-O-GlcNAcylation-YBX1 axis promotes IL-18 secretion to regulate the tumor immune microenvironment in pancreatic cancer.

The immunosuppressive microenvironment caused by several intrinsic and extrinsic mechanism has brought great challenges to the immunotherapy of pancreatic cancer. We identified GFPT2, the key enzyme in hexosamine biosynthesis pathway (HBP), as an immune-related prognostic gene in pancreatic cancer using transcriptome sequencing and further confirmed that GFPT2 promoted macrophage M2 polarization and malignant phenotype of pancreatic cancer. HBP is a glucose metabolism pathway leading to the generation of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), which is further utilized for protein O-GlcNAcylation. We confirmed GFPT2-mediated O-GlcNAcylation played an important role in regulating immune microenvironment. Through cellular proteomics, we identified IL-18 as a key downstream of GFPT2 in regulating the immune microenvironment. Through CO-IP and protein mass spectrum, we confirmed that YBX1 was O-GlcNAcylated and nuclear translocated by GFPT2-mediated O-GlcNAcylation. Then, YBX1 functioned as a transcription factor to promote IL-18 transcription. Our study elucidated the relationship between the metabolic pathway of HBP in cancer cells and the immune microenvironment, which might provide some insights into the combination therapy of HBP vulnerability and immunotherapy in pancreatic cancer.

Focus on mast cells in the tumor microenvironment: Current knowledge and future directions.

Mast cells (MCs) are crucial cells participating in both innate and adaptive immune processes that play important roles in protecting human health and in the pathophysiology of various diseases, such as allergies, cardiovascular diseases, and autoimmune diseases. In the context of tumors, MCs are a non-negligible population of immune cells in the tumor microenvironment (TME). In most tumor types, MCs accumulate in both the tumor tissue and the surrounding tissue. MCs interact with multiple components of the TME, affecting TME remodeling and the tumor cell fate. However, controversy persists regarding whether MCs contribute to tumor progression or trigger an anti-tumor immune response. This review focuses on the context of the TME to explore the specific properties and functions of MCs and discusses the crosstalk that occurs between MCs and other components of the TME, which affect tumor angiogenesis and lymphangiogenesis, invasion and metastasis, and tumor immunity through different mechanisms. We also anticipate the potential role of MCs in cancer immunotherapy, which might expand upon the success achieved with existing cancer therapies.

Knockdown of TACC3 inhibits tumor cell proliferation and increases chemosensitivity in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant digestive tract tumor with limited clinical treatments. Transforming acidic coiled-coil-containing protein 3 (TACC3) is a component of the centrosome axis and a member of the TACC family, which affect mitosis and regulate chromosome stability and are involved in tumor development and progression. However, the role of TACC3 in PDAC remains elusive. In this study, by exploiting the TCGA database, we found that high TACC3 expression in PDAC is associated with poor prognosis. shRNA-mediated TACC3 knockdown caused S phase arrest of the cell cycle and inhibited proliferation in PDAC cell lines. Through RNA sequencing and protein co-immunoprecipitation combined with mass spectrometry, KIF11 was identified as a protein that interacts with TACC3. TACC3 stabilizes and regulates KIF11 protein expression levels in PDAC cells through physical interaction. Knockdown of TACC3 or KIF11 resulted in abnormal spindle formation during cell division both in vitro and in vivo. Pharmacological inhibition of TACC3 or KIF11 can suppress tumor cell proliferation and promote apoptosis. Our studies further demonstrated that high expression of TACC3 and KIF11 mediated the resistance of PDAC to gemcitabine, and deficiency of TACC3 or KIF11 increased the sensitivity of PDAC cells to chemotherapy. In conclusion, our study reveals the fundamental role of TACC3 expression in PDAC cell proliferation and chemoresistance, suggesting that TACC3 can be used as a molecular marker to evaluate the prognosis of PDAC.