The Journal retracts the article “Inhibition of AKT2 Enhances Sensitivity to Gemcitabine via Regulating PUMA and NF-κB Signaling Pathway in Human Pancreatic Ductal Adenocarcinoma” [...]

BackgroundNeoadjuvant radiotherapy represents a conventional approach for managing locally advanced rectal carcinoma. Although this regimen has many benefits, radiation injury is associated with intestinal mucosal injury and gut microbiota dysbiosis. The long-term dynamics of inflammation and microbial recovery, including oral microbiota alterations, remain unclear.MethodsIntestinal mucosal specimens were obtained from patients with rectal cancer who underwent surgical treatment without radiotherapy or at predetermined time intervals (4 ± 1 weeks, 8 ± 1 weeks and 12 ± 1 weeks) after radiotherapy. The levels of TNF-α, IL-4 and IL-6 in the intestinal mucosa were determined using ELISA. Meanwhile, the intestinal mucosa and saliva of 18 recruited rectal cancer patients were subjected to 16S rRNA gene sequencing (radiotherapy group, n=9; non-radiotherapy group, n=9) for analysis of the gut and oral microbial communities.ResultsMucosal IL-4 levels were still significantly elevated at 12 weeks post-radiotherapy with respect to the non-radiotherapy group (p<0.05), while TNF-α and IL-6 were back at baseline levels. The gut microbiota composition of radiotherapy patients differed from that of non-radiotherapy patients, with a significant reduction in Chao1 diversity index (p<0.01) and distinct β-diversity clustering (ANOSIM R = 0.614, p=0.001). These differences were still present at 12 weeks post radiotherapy. The oral microbiota changes were limited, with only a few taxa that showed significant differences (ANOSIM R = 0.38, p=0.009).ConclusionNeoadjuvant radiotherapy is associated with persistent intestinal mucosa inflammation and prolonged disruption of gut microbiota and this dysbiosis does not fully normalize within 12 weeks after treatment. Changes in oral microbiota appeared less pronounced. These findings provide the biological context for understanding intestinal recovery after radiotherapy and indicate that more studies are needed to direct future efforts towards the peri-operative manipulation of gut microbiota.

BACKGROUND:In a bridging study of INTRIGUE, second-line ripretinib demonstrated comparable progression-free survival (PFS) and favorable safety versus sunitinib in Chinese patients with advanced gastrointestinal stromal tumor. Overall survival (OS) was highly immature at the time of primary analysis. This updated analysis assessed long-term OS of ripretinib versus sunitinib. METHODS:This phase 2, multicenter, randomized, open-label study in China enrolled patients with gastrointestinal stromal tumor previously treated with imatinib, randomized (1:1) to ripretinib 150 mg once daily by continuous dosing in 42-day cycles or sunitinib 50 mg once daily in 42-day cycles (four weeks on/two weeks off). The updated analysis assessed OS and PFS on third-line therapy in all-patient intention-to-treat and KIT exon 11-mutated intention-to-treat (Ex11 ITT) populations. RESULTS:Of 108 patients randomized, 54 received ripretinib and 54 sunitinib; 70 had a primary KIT exon 11 mutation (ripretinib, n = 35; sunitinib, n = 35; Ex11 ITT). By December 30, 2024, in all-patient intention-to-treat population, median OS was 43.3 months with ripretinib and 29.9 months with sunitinib (hazard ratio, 0.681; 95% CI, 0.411-1.126; nominal p = .134). In the Ex11 ITT population, median OS was 43.3 months with ripretinib and 28.6 months with sunitinib (hazard ratio, 0.552; 95% CI, 0.291-1.047; nominal p = .065). PFS on third-line therapy was comparable between treatment arms in both populations. CONCLUSIONS:After two additional years of follow-up, ripretinib showed a trend toward clinically meaningful OS benefit versus sunitinib in the Ex11 ITT population. Second-line ripretinib does not appear to affect third-line treatment efficacy.

Purpose:Colorectal cancer (CRC) is still one of the most common malignant tumors, with gradual increase in its annual morbidity and mortality. But most cases are diagnosed in the late stage. For stage II-III cancer, clinical guidelines recommend surgery following neoadjuvant radiation therapy at ≥6 weeks after the last radiotherapy is completed. However, radiotherapy may impair intestinal mucosal barrier function, especially the biological and immune barriers, accompanied by perioperative complications. This study was conducted to investigate the changes, repair patterns, and potential mechanisms in patients after radiotherapy. Methods:This study detected inflammatory factors in postoperative intestinal mucosal tissue and serum, as well as metabolites in saliva samples, and collected hematoxylin-eosin (HE)-stained pathological images in CRC patients who had received and did not receive radiotherapy. Results:The results showed that after radiotherapy, there were significantly impaired intestinal mucosal tissue structure; obviously elevated inflammatory factors in intestinal mucosal tissue and blood; as well as upregulation/downregulation of metabolites in saliva samples. Conclusion:In conclusion, findings in this study may provide potential reference for predicting the recovery of intestinal mucosa and selecting the optimal timing for surgery after radiotherapy. In addition, this study will benefit the understanding and reduction of perioperative complications caused by intestinal barrier damage.

IntroductionColorectal cancer (CRC) is the third most common malignant tumor, and neoadjuvant chemo-radiotherapy is usually recommended for advanced stage colorectal cancer. Radiotherapy can cause damage to intestinal mucosal barrier, which may be related to perioperative complications. Intestinal microbiota is one of the constituents of the intestinal mucosal biological barrier, and literature reports that patients with CRC have changes in corresponding oral microbiota. This study aims to analyze the levels of immunoglobulin SIgA, inflammatory factors, lymphocyte subsets quantity, and proportion in surgical specimens of intestinal mucosa at different time intervals after radiotherapy, in order to seek investigation for the optimal surgical time after radiotherapy and to provide evidence for finding probiotics or immunomodulators through high-throughput sequencing of bacterial 16s rRNA in patients' saliva microbiota. Ultimately, this may provide new ideas for reducing perioperative complications caused by radiotherapy-induced intestinal damage.MethodsWe selected intestinal mucosal tissue and saliva samples from over 40 patients in our center who did not undergo radiotherapy and underwent surgery at different time intervals after radiotherapy. Detection of SIgA was performed using ELISA assay. Western Blotting was used to detect IL-1β, IL-6, and IL-17 in the intestinal mucosal tissue. Flow cytometry was used to detect CD4 and CD8. And the microbial community changes in saliva samples were detected through 16s rRNA sequencing.ResultsAfter radiotherapy, changes in SIgA, various cytokines, CD4CD8 lymphocyte subsets, and oral microbiota in the intestinal mucosal tissue of rectal cancer patients may occur. Over time, this change may gradually recover.DiscussionIn colorectal cancer, oncological aspects often receive more attention, while studies focusing on the intestinal mucosal barrier are less common. This study aims to understand the repair mechanisms of the intestinal mucosal barrier and reduce complications arising from radiotherapy-induced damage. The relationship between oral microbiota and systemic diseases has gained interest in recent years. However, the literature on the oral microbiota after radiotherapy for rectal cancer remains scarce. This study addresses this gap by analysing changes in the salivary microbiota of rectal cancer patients before and after radiotherapy, shedding light on microbiota changes. It aims to lay the groundwork for identifying suitable probiotics or immunomodulators to alleviate perioperative complications and improve the prognosis of CRC.

The heterogeneous nature of tumors presents a considerable obstacle in addressing imatinib resistance in advanced cases of gastrointestinal stromal tumors (GIST). To address this issue, we conducted single-cell RNA-sequencing in primary tumors as well as peritoneal and liver metastases from patients diagnosed with locally advanced or advanced GIST. Single-cell transcriptomic signatures of tumor microenvironment (TME) were analyzed. Immunohistochemistry and multiplex immunofluorescence staining were used to further validate it. This analysis revealed unique tumor evolutionary patterns, transcriptome features, dynamic cell-state changes, and different metabolic reprogramming. The findings indicate that in imatinib-resistant TME, tumor cells with activated immune and cytokine-mediated immune responses interacted with a higher proportion of Treg cells via the TIGIT-NECTIN2 axis. Future immunotherapeutic strategies targeting Treg may provide new directions for the treatment of imatinib-resistant patients. In addition, IDO1+ dendritic cells (DC) were highly enriched in imatinib-resistant TME, interacting with various myeloid cells via the BTLA-TNFRSF14 axis, while the interaction was not significant in imatinib-sensitive TME. Our study highlights the transcriptional heterogeneity and distinct immunosuppressive microenvironment of advanced GIST, which provides novel therapeutic strategies and innovative immunotherapeutic agents for imatinib resistance.

Objective The objective of this study was compare the effects of robot-assisted and laparoscopic-assisted surgery on lymph node dissection and quality of life in upper third gastric cancer patients undergoing radical total gastrectomy. Methods The clinical and follow-up data of 409 patients with upper third gastric cancer who underwent total gastrectomy from July 2016 to May 2021 were enrolled. The patients were divided into a robotic group (n = 106) and a laparoscopic group (n = 303). Age, sex, body mass index, American Society of Anesthesiologists score, tumor size and location, pathological type, cT, cN, and cTNM were adjusted to offset selection bias. The patient characteristics, operative procedures, surgical outcomes, oncologic and pathologic outcomes, number of lymph node dissections, quality of life assessment, and nutritional status were compared between the two groups. Results After propensity score matching, 61 cases were included in the robotic group and 122 cases were included in the laparoscopic group. The number of dissected lymph nodes (37.3 ± 13.5 vs. 32.8 ± 11.8, P = 0.022) significantly differed between the two groups. The number of lower mediastinal and subphrenic lymph nodes in the robotic group was greater than that in the laparoscopic group, and the difference was statistically significant (P < 0.001). Compared with the laparoscopic group, the total score of physical symptoms in the robotic group was significantly lower at 6 and 12 months after surgery (P = 0.03 and P = 0.001, respectively). The total social function score at 6 and 12 months after surgery was higher in the robotic group (P = 0.006 and P = 0.022). The quality of life scores were statistically significant only at 3 months after the operation (P = 0.047). A higher patient-generated subjective global assessment (PG-SGA) score is when the score significantly correlated (P < 0.001) with a higher related physical symptoms score, lower social function score, and lower quality of life score. Conclusion Compared with laparoscopic radical gastrectomy, robotic radical gastrectomy is safe and feasible. Compared with laparoscopic radical gastrectomy, robotic radical gastrectomy was more refined, was associated with less surgical bleeding, and increased the quality of lymph node dissection. In addition, patients in the robotic group showed better postoperative quality of life.

AbstractBackgroundAnlotinib is a multi-target tyrosine kinase inhibitor that can effectively inhibit tumor cell proliferation after receptor kinase activation caused by KIT gene mutation.MethodsWe tested the inhibitory effect of anlotinib in GIST cell lines with different gene mutations and evaluated the efficacy of anlotinib for patients with metastatic GIST after imatinib failure in a multicenter, single-arm, phase II study.ResultsIn vitro, V654A mutation encoded by KIT exon 13 was intermediately sensitive to anlotinib. Moreover, anlotinib was able to partly suppress the activation loop mutation D820A from exon 17 while another activation loop mutation N822K, also from exon 17, was resistant to anlotinib. From September 2018 to October 2020, 64 patients from 9 Chinese medical centers were enrolled in this study. Seven patients had partial response and 39 patients had stable disease. The median PFS was 8.0 months. There was no statistical significance comparing with PFS of sunitinib second-line therapy at the same period. The most common adverse events related to anlotinib treatment were hypertension, neutropenia, and fatigue.ConclusionAnlotinib showed moderate antitumor activity in drug-resistant GIST cell lines in vitro, and good PFS and better tolerance in second-line therapy study.

Background Proximal gastrectomy with gastric tubular reconstruction is a surgical procedure that can preserve function in patients with proximal gastric cancer. However, whether gastric tubular reconstruction with proximal gastrectomy has certain advantage in some aspects over total gastrectomy is controversial. To evaluate the benefit of gastric tubular reconstruction after proximal gastrectomy, we compared gastric tubular reconstruction with total gastrectomy for proximal gastric cancer. Method A total of 351 patients were enrolled. Concurrent total gastrectomy patients matched with the Proximal gastrectomy group in age, sex, body mass index, clinical stage, and ASA score were selected by propensity score matching. Preoperative basic information, perioperative indicators, histopathological features, postoperative complications and nutritional status, reflux were compared between the two groups. Results There was no significant difference in the incidence of reflux between two groups (14.8% and 6.5% respectively, P = 0.085). There were significant differences between the two groups in bowel function recovery (2.29 ± 1.16 vs. 3.01 ± 1.22; P = 0.039) and start of soft diet (4.06 ± 1.81 vs. 4.76 ± 1.69; P = 0.047). There were no significant differences between the two groups in nutritional status one year after surgery. However, the decrease in serum hemoglobin in the TG group at 3 and 6 months after surgery was significantly higher than that in the PG group ( P = 0.032 and 0.046, respectively). One month after surgery, %BW loss in TG group was significantly lower than that in the PG group ( P = 0.024). Conclusion The Proximal gastrectomy group has better clinical outcome and gastric tubular reconstruction is simple, similar complications and reflux rates, gastric tubular reconstruction may be more suitable for proximal gastric cancer.

BackgroundColon cancer is a highly heterogeneous disease, and identifying molecular subtypes can provide insights into deregulated pathways within tumor subsets, which may lead to personalized treatment options. However, most prognostic models are based on single-pathway genes.MethodsIn this study, we aimed to identify three clinically relevant subtypes of colon cancer based on multiple signaling pathways-related genes. Integrative multi-omics analysis was used to explain the biological processes contributing to colon cancer aggressiveness, recurrence, and progression. Machine learning methods were employed to identify the subtypes and provide medication guidance for distinct subtypes using the L1000 platform. We developed a robust prognostic model (MKPC score) based on gene pairs and validated it in one internal test set and three external test sets. Risk-related genes were extracted and verified by qPCR.ResultsThree clinically relevant subtypes of colon cancer were identified based on multiple signaling pathways-related genes, which had significantly different survival state (Log-Rank test, p<0.05). Integrative multi-omics analysis revealed biological processes contributing to colon cancer aggressiveness, recurrence, and progression. The developed MKPC score, based on gene pairs, was robust in predicting prognosis state (Log-Rank test, p<0.05), and risk-related genes were successfully verified by qPCR (t test, p<0.05). An easy-to-use web tool was created for risk scoring and therapy stratification in colon cancer patients, and the practical nomogram can be extended to other cancer types.ConclusionIn conclusion, our study identified three clinically relevant subtypes of colon cancer and developed a robust prognostic model based on gene pairs. The developed web tool is a valuable resource for researchers and clinicians in risk scoring and therapy stratification in colon cancer patients, and the practical nomogram can be extended to other cancer types.

803 Background: Ripretinib is a switch-control tyrosine kinase inhibitor approved for the fourth-line therapy for GIST. In the INTRIGUE study (NCT03673501), ripretinib as second-line (2L) treatment demonstrated similar progression-free survival (PFS) and fewer Grade 3/4 treatment-emergent adverse events (TEAEs) compared to sunitinib in the overall population. It showed a numerically longer PFS and a nominally higher objective response rate (ORR) than sunitinib in patients (pts) with KIT exon 11 mutations. This study aims to evaluate the efficacy and safety of ripretinib vs sunitinib as 2L treatment in GIST pts in China. Methods: This multicenter, randomized, open-label phase 2 study (NCT04633122) enrolled adults with GIST who progressed on or had intolerance to imatinib. Pts were randomized 1:1 to ripretinib 150 mg once daily (QD) or sunitinib 50 mg QD (4 weeks on/2 weeks off) in 42-day cycles. Randomization was stratified by KIT mutational status. The primary endpoint was PFS by independent radiologic review (IRR) using modified RECIST version 1.1. Secondary endpoints included ORR by IRR, overall survival (OS) and safety. Efficacy analysis was performed in all-patients intent-to-treat (AP ITT) and KIT exon 11 mutation intent-to-treat (Ex11 ITT) populations. This study was designed to bridge the global trial (INTRIGUE) to show consistency in the efficacy of ripretinib between the two studies. No statistical testing was pre-specified and nominal p-values were presented for descriptive purpose. Results: Overall, 108 pts were randomized to ripretinib (AP ITT n= 54; Ex11 ITT n=35) or sunitinib (AP ITT n= 54; Ex11 ITT n=35). Median age was 59.0 years (range 25–82); 63.9% of pts were male and 57.4% had ECOG PS≥1. By primary data cut-off (20 Jul 2022), PFS by IRR was similar between ripretinib and sunitinib in AP ITT population (HR 0.99, 95% CI 0.57, 1.69; p=0.92; median PFS [mPFS] 10.3 vs 8.3 months). ORR by IRR was numerically higher for ripretinib than sunitinib (29.6% vs 20.4%). Median OS was not reached in either arm. In Ex11 ITT population, a longer PFS by IRR (HR 0.46, 95% CI 0.23, 0.92; p=0.03; mPFS not reached for ripretinib and 4.9 months for sunitinib) and a numerically higher ORR by IRR (37.1% vs 22.9%) were observed for ripretinib vs sunitinib. Fewer Grade 3/4 treatment-related TEAEs were reported with ripretinib than with sunitinib (16.7% vs 55.6%), as were treatment-related TEAEs leading to dose interruption (7.4% vs 42.6%), dose reduction (20.4% vs 29.6%) and treatment discontinuation (1.9% vs 7.4%). Conclusions: Similar to the INTRIGUE trial, ripretinib demonstrated comparable overall efficacy and favorable safety vs sunitinib as 2L therapy in Chinese pts with advanced GIST. 2L GIST pts harboring a KIT exon 11 mutation may benefit from ripretinib vs sunitinib. Clinical trial information: NCT04633122 .

This publication has been retracted by the Editor due to the identification of falsified figure images and manuscript content that raise concerns regarding the credibility of the study and the manuscript. Reference: Vemurafenib Hao Song, Jinna Zhang, Liang Ning, Honglai Zhang, Dong Chen, Xuelong Jiao, Kejun Zhang. The MEK1/2 Inhibitor AZD6244 Sensitizes BRAF-Mutant Thyroid Cancer to Vemurafenib. Med Sci Monit, 2018; 24: 3002-3010. DOI: 10.12659/MSM.910084.

BackgroundAdjuvant imatinib therapy has been shown to improve overall survival (OS) of gastrointestinal stromal tumor (GIST) significantly. Few nomograms combining the use of adjuvant imatinib and clinicopathological characteristics estimate the outcome of patients. We aimed to establish a more comprehensive nomogram for predicting OS in patients with GIST.MethodsIn total, 1310 GIST patients undergoing curative resection at four high-volume medical centers between 2001 and 2015 were enrolled. Independent prognostic factors were identified by multivariate Cox analysis. Eligible patients were randomly assigned in a ratio of 7:3 into a training set (916 cases) and a validation set (394 cases). A nomogram was established by R software and its predictive power compared with that of the modified National Institutes of Health (NIH) classification using time-dependent receiver operating characteristic (ROC) curves and calibration plot.ResultsAge, tumor site, tumor size, mitotic index, postoperative imatinib and diagnostic delay were identified as independent prognostic parameters and used to construct a nomogram. Of note, diagnostic delay was for the first time included in a prognostic model for GIST. The calibrated nomogram resulted in predicted survival rates consistent with observed ones. And the decision curve analysis suggested that the nomogram prognostic model was clinically useful. Furthermore, time-dependent ROC curves showed the nomogram exhibited greater discrimination power than the modified NIH classification in 3- and 5-year survival predictions for both training and validation sets (all P < 0.05).ConclusionsPostoperative adjuvant imatinib therapy improved the survival of GIST patients. We developed and validated a more comprehensive prognostic nomogram for GIST patients, and it could have important clinical utility in improving individualized predictions of survival risks and treatment decision-making.

miR-199a-5p suppresses epithelialmesenchymal-transition in anaplastic thyroid carcinoma cells via targeting Snail signals Fengyun Haoa, Ya-Nan Bib, Lei Wangc, Yubing Wangc, Jilei Mac, Ping Cuic, Xuhua Lic, Shukai Sund, Liang Ninge, Yichuan Huanga, Xuelong Jiaoe,* and Dong Chene,* aDepartment of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China bOperating Room, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China cThyroid Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China dClinical Lab, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China eGeneral Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China

BACKGROUND Nomograms for prognosis prediction in colorectal cancer patients are few, and prognostic indicators differ with age. AIM To construct a new nomogram survival prediction tool for middle-aged and elderly patients with stage III rectal adenocarcinoma. METHODS A total of 2773 eligible patients were divided into the training cohort (70%) and the validation cohort (30%). Optimal cutoff values were calculated using the X-tile software for continuous variables. Univariate and multivariate Cox proportional hazards regression analyses were used to determine overall survival (OS) and cancer-specific survival (CSS)-related prognostic factors. Two nomograms were successfully constructed. The discriminant and predictive ability and clinical usefulness of the model were also assessed by multiple methods of analysis. RESULTS The 95%CI in the training group was 0.719 (0.690-0.749) and 0.733 (0.702-0.74), while that in the validation group was 0.739 (0.696-0.782) and 0.750 (0.701-0.800) for the OS and CSS nomogram prediction models, respectively. In the validation group, the AUC of the three-year survival rate was 0.762 and 0.770, while the AUC of the five-year survival rate was 0.722 and 0.744 for the OS and CSS nomograms, respectively. The nomogram distinguishes all-cause mortality from cancer-specific mortality in patients with different risk grades. The time-dependent AUC and decision curve analysis showed that the nomogram had good clinical predictive ability and decision efficacy and was significantly better than the tumor-node-metastases staging system. CONCLUSION The survival prediction model constructed in this study is helpful in evaluating the prognosis of patients and can aid physicians in clinical diagnosis and treatment.

Cancer is the leading cause of death worldwide. The absence of obvious symptoms and insufficiently sensitive biomarkers in early stages of carcinoma limits early diagnosis. Cancer therapy agents and targeted therapy have been used extensively against tissues or organs of specific cancers. However, the intrinsic and/or acquired resistance to the agents or targeted drugs as well as the serious toxic side effects of the drugs would limit their use. Therefore, identifying biomarkers involved in tumorigenesis and progression represents a challenge for cancer diagnosis and therapeutic strategy development. The eukaryotic translation factor 5A (eIF5A), originally identified as an initiation factor, was later shown to promote translation elongation of iterated proline sequences. There are two eIF5A isoforms (eIF5A1 and eIF5A2). eIF5A2 protein consists of 153 residues, and shares 84% amino acid identity with eIF5A1. However, the biological functions of these two isoforms may be significantly different. Recently, it was demonstrated that eIF5Ais widely involved in the pathogenesis of a number of diseases, including cancers. In particular, eIF5A plays an important role in regulating tumor growth, invasion, metastasis and tumor microenvironment. It was also shown to serve as a potential biomarker and target for the diagnosis and treatment of cancers. The present review briefly discusses the latest findings of eIF5A in the pathogenesis of certain malignant cancers and evolving clinical applications.

目的:观察γ射线照射对Slug敲除C57BL/6小鼠肠粘膜上皮细胞损伤的影响及机制.方法:Slug敲除C57BL/6小鼠和非Slug敲除C57BL/6小鼠各12只,以8Gy60Coγ射线全身一次性照射制作动物模型,分别在照射后第1、3、8天处死小鼠,取小肠组织4％多聚甲醛液固定作病理学检查;取非Slug基因敲除小鼠和Slug基因敲除小鼠各24只,予以8Gy60Coγ射线全身一次性照射,分别在照射后第2、4和24 h处死,采用免疫组化法检测肠道细胞PUMA表达,TUNEL染色检测细胞凋亡.结果:8Gy60Coγ射线照射后,Slug基因敲除小鼠死亡率91.67％,明显高于非基因敲除小鼠的25.00％,差异有统计学意义(P=0.004).Slug敲除小鼠肠道细胞凋亡指数、PUMA阳性表达细胞数以及肠道损伤的严重程度均明显高于非敲除组.结论:Slug基因敲除加重γ射线引起的放射性肠道损伤.

Anaplastic thyroid carcinoma (ATC) is resistant to standard therapies and has no effective treatment. Eukaryotic translation initiation factor 5A2 (EIF5A2) has shown to be upregulated in many malignant tumors and proposed to be a critical gene involved in tumor metastasis. In this study, we aimed to investigate the expression status of EIF5A2 in human ATC tissues and to study the role and mechanisms of EIF5A2 in ATC tumorigenesis in vitro and in vivo. Expression of EIF5A2 protein was analyzed in paraffin-embedded human ATC tissues and adjacent nontumorous tissues (ANCT) ( n =24) by immunochemistry. Expressions of EIF5A2 mRNA and protein were analyzed in fresh-matched ATC and ANCT ( n =23) and ATC cell lines by real-time polymerase chain reaction (PCR) and Western blotting. The effect of targeting EIF5A2 with short hairpin RNA (shRNA) or EIF5A2 overexpression on the ATC tumorigenesis and TGF-/Smad2/3 signals in vitro and in vivo was investigated. Expression of EIF5A2 was significantly upregulated in ATC tissues and cell lines compared with ANCT and normal follicular epithelial cell line. Functional studies found that targeting EIF5A2 induced SW1736 cell death in vitro and in vivo, followed by significantly downregulated phosphorylation of Smad2/3 (p-Smad2/3) in SW1736 cells at the protein level. Ectopic expression of EIF5A2 could promote 8505C cell growth in vitro and in vivo, followed by significantly upregulated p-Smad3 at the protein level. Recombinant human TGF-1 (hTGF-1) treatment decreased the antiproliferative activity of the EIF5A2 downexpressing 8505C cells through reversing pSmad2/3. Using the specific inhibitor SB431542 to block TGF- pathway or Smad3 siRNA to knock down Smad3 increased the antiproliferative activity of the EIF5A2-overexpressing 8505C cells through inhibiting pSmad2/3. Our findings indicated that EIF5A2 controled cell growth in ATC cells, and EIF5A/TGF-/Smad2/3 signal may be a potential therapeutic target for ATC treatment.