The activation of adenosine monophosphate–activated protein kinase inhibits the migration of tongue squamous cell carcinoma cells by targeting Claudin-1 via epithelial–mesenchymal transition

Background:The role of Claudin-1 in tongue squamous cell carcinoma(TSCC)metastasis needs further clarification,particularly its impact on cell migration.Herein,our study aims to investigate the role of Claudin-1 in TSCC cell migration and its underlying mechanisms.Methods:36 TSCC tissue samples underwent immunohistochemical staining for Claudin-1.Western blotting and immunofluorescence analyses were conducted to evaluate Claudin-1 expression and distribution in TSCC cells.Claudin-1 knockdown cell lines were established using short hairpin RNA transfection.Migration effects were assessed through wound healing assays.Furthermore,the expression of EMTassociated molecules was measured via western blotting.Results:Claudin-1 expression decreased as TSCC malignancy increased.Adenosine monophosphate–activated protein kinase(AMPK)activation led to increased Claudin-1 expression and membrane translocation,inhibiting TSCC cell migration and epithelial–mesenchymal transition(EMT).Conversely,Claudin-1 knockdown reversed these inhibitory effects on migration and EMT caused by AMPK activation.Conclusions:Our results indicated that AMPK activation suppresses TSCC cell migration by targeting Claudin-1 and EMT pathways.

Acute severe hypokalemia caused by treatment of tongue squamous cell carcinoma with docetaxel and cisplatin:A case report

BACKGROUND The tongue squamous cell carcinoma(TSCC)is an oral malignant tumor arising from the squamous epithelium of the tongue mucosa,characterized by a high malignant degree,invasive growth,early lymph node metastasis,and poor prognosis.Paclitaxel,represented by docetaxel,is now the standard first-line treatment for head and neck squamous cell carcinoma.Docetaxel,which belongs to the class of drugs known as paclitaxel,is an antitumor drug that inhibits cell mitosis and proliferation.Its adverse effects include myelosuppression,hair loss,gastrointestinal reactions,fluid retention,and allergic reactions.However,hypokalemia is rare,most cases are mild or moderate,and severe hypokalemia is seldom reported.symptoms of adverse effects early.It is necessary to be considerate regarding individual differences between patients when selecting chemotherapy regimens and adhere to the principle of individualized treatment.Following multiple cycles of chemotherapy,patients should be aware of the accumulation of toxic side effects and receive blood tests reviewed within 24 hours of completion.It is essential to monitor electrolyte levels in patients suffering from severe gastrointestinal reactions to avoid complications that may result in death.

Current Research Status of MicroRNAs in Squamous Cell Carcinoma of the Tongue

Tongue squamous cell carcinoma (TSCC) is the most invasive type of oral malignant tumor, posing a serious threat to human life and health. Its pathogenesis is complex and has a high degree of malignancy. Recurrence and metastasis often lead to poor prognosis. MicroRNAs are a type of single stranded small molecule RNA with only 18 - 25 nucleotides, which can regulate the expression of various genes and participate in the occurrence and development of tumors. Studies have found that microRNA expression profiling can serve as a reliable and stable biological indicator for early diagnosis and prognosis of tumors. This article provides a review of the research status of MicroRNAs in squamous cell carcinoma of the tongue.

In vitro effect of iASPP on cell growth of oral tongue squamous cell carcinoma

iASPP is an inhibitory member of the apoptosis-stimulating proteins of P53 （ASPP） family. iASPP is over expressed in several malignant tumors and potentially affects cancer progression. However, the expression and potential role of iASPP in oral tongue squamous cell carcinoma （OTSCC） have not been addressed. In our study, we detected iASPP expression in OTSCC by immunohistochemistry, iASPP expression is up-regulated in OTSCC tissues. Moreover, in clinical pathology specimens, we found that increased iASPP expression correlates with poor differentiation and lymph node metastasis. Using multicellular tumor spheroids （MTS） and flow cytometry, we demonstrated that iASPP down-regulation arrests OTSCC cells at the G0/G1 phase, induces OTSCC cell apoptosis and inhibits OTSCC cell proliferation. These results indicate that iASPP plays a significant role in the progression of OTSCC and may serve as a biomarker or therapeutic target for OTSCC patients.

MiR-25-3p attenuates the proliferation of tongue squamous cell carcinoma cell line Tca8113

Objective:To investigate the effects of miR-25-3p on the occurrence,development and proliferation of tongue squamous cell carcinoma cells.Methods:To establish tongue squamous cell carcinoma cell line Tca8113 that stably and highly express miR-25-3p using recombinant reiroviral vector-mediated gene transfer method.The proliferation of transfected Tca8113 was detected by thiazolyl blue tetrazolium bromide(MTT)and cell colony formation assays.eyclnD1,p21^(cipt)and p27^(kipt)mRNA expressions in the transfected Tca-8113 were detected by quantitative PCR.cyclinD1,p21^(cipt),p27^(kipt),AKT,p-AKT,FOXOt and p-FOX01 expressions in the transfected Tca8113 were detected by western blot analysis.In addition,miR-25-3p expression in the tongue squamous cell carcinoma cell line and tissue specimen was also detected by quantitative PCR.Results:Quantitative PCR showed that mitt-25-3p expression in the tongue squamous cell carcinoma cell lines and tissue specimen was significantly lower than that in the adjacent tissue.MTT and cell colony formation assays showed that after miR-25-3p overexpression,the proliferation of transfected Tca8113 was obviously attenuated.Western blot analysis and quantitative PCR showed that after miR-25-3p overexpression.p21^(cipt)and p27^(kipt)expressions were upregulated,while cyclinD1,AKT,FOXO1 expressions were downregulated,and AKT and FOXO1 phosphorylation was inactivated in the transfected Tca8113 cells.Conclusions:MiR-25-3p inhibited the proliferation of tongue squamous cell carcinoma cells and regulated cell cycle-related protein expression,playing an important role in the occurrence and development of squamous cell carcinoma of the tongue.

OCCULT CERVICAL METASTASIS OF SQUAMOUS CELL CARCINOMA OF TONGUE AMONG CN0 PATIENTS AND ITS TREATMENT

Objective： To explore the treatment of clinically negative neck （CN0） patients with squamous cell carcinoma of the tongue. Methods： 165 CN0 patients with squamous cell carcinoma of the tongue from 1985 to 2002 were investigated retrospectively. Parts of the patients staged at T1, T2 and T3 underwent resection of primary lesion followed by neck observation, and other patients staged above T2 or at T1 but without follow-up were treated with elective neck dissection （END）. All patients were followed up for more than 3 y or until their death. Results： Lymphatic metastasis was identified histologically after operation in 33 of 120 patients treated with END, and 9 of 45 patients treated with resection of primary lesion alone. The overall rate of occult lymphatic metastasis was 25.45%, which increased with the elevating of clinical T stage. The overall rate of neck uncontrolled death was 20.00% for observation group and 5.00% for END group, and significant difference was found between them （P〈0.05）. For T~ patients in the two groups, the rate of neck uncontrolled death was 7.71% and 4.00% respectively, and no significance was found between them （P〉0.05）. When stage T2 and T3 were considered as middle stage together, significant difference （P〈0.05） could be obtained between observation （70.00%） and END group （0%）. Conclusion： The occult metastasis rate of squamous cell carcinoma of tongue increases with the elevating of clinical stage, and elective neck dissection could be considered for NO patients staged over T2 to improve neck control and survival rate; and regional resection alone of primary lesion could be considered for T1N0 patients to improve quality of life if closely followed up is conducted.

Molecular signaling in cancer stem cells of tongue squamous cell carcinoma:Therapeutic implications and challenges

Head and neck squamous cell carcinoma is the seventh most common cancer worldwide with high mortality rates.Amongst oral cavity cancers,tongue carcinoma is a very common and aggressive oral cavity carcinoma.Despite the implementation of a multimodality treatment regime including surgical intervention,chemo-radiation as well as targeted therapy,tongue carcinoma shows a poor overall 5-year survival pattern,which is attributed to therapy resistance and recurrence of the disease.The presence of a rare population,i.e.,cancer stem cells(CSCs)within the tumor,are involved in therapy resistance,recurrence,and distant metastasis that results in poor survival patterns.Therapeutic agents targeting CSCs have been in clinical trials,although they are unable to reach into therapy stage which is due to their failure in trials.A more detailed understanding of the CSCs is essential for identifying efficient targets.Molecular signaling pathways,which are differentially regulated in the CSCs,are one of the promising targets to manipulate the CSCs that would provide an improved outcome.In this review,we summarize the current understanding of molecular signaling associated with the maintenance and regulation of CSCs in tongue squamous cell carcinoma in order to emphasize the need of the hour to get a deeper understanding to unravel novel targets.

Neoneurogenesis in Squamous Cell Carcinoma of Tongue: A New Mechanism for Its Development

Objectives: To explore the role of the growth of new nerves (neo-neurogenesis) in the tumorogenesis of squamous cell carcinoma of tongue. Materials and Methods: 10 formalin-fixed specimens were gained from patients diagnosed with tongue squamous cell carcinoma. Animal models were made by subcutaneous injection in the dorsal midline with Tca-8113 cell line. Mice were sacrificed 2, 4, 6 weeks after cell injection, and tumor tissues were fixed in 4% paraformaldehyde, embedded in paraffin, sectioned. Detection of neo-neurogenesis was stained by Neurofila-ment-L antibody (NF-L) using immunohistochemistry method (IHC) in biopsy from both human body and animal model. Results: IHC staining of NF-L is positive in all 10 paraffins of tongue squamous cell carcinoma sections which suggest that newly formed nerves are observed in tumor microenvironment. NF-L staining is also positive in the paraffins from animal models indicating that the tongue cancer recruits newly formed nerves in its tumorogenesis. Conclusions: Tumor neo-neurogenesis may play an important role in the pathogenesis and development of tongue cancer. From a therapeutic perspective, further studies on the topic may provide new clinical opportunity.

EXPRESSION OF c-erbB-2, p53, p16 IN SQUAMOUS CELL CARCINOMA OF ANTERIOR TONGUE IN CHINA POPULATION

Objective: Aberrant expression of c-erbB-2, p53, p16 has been found in oral squamous cell carcinoma. We therefore examined expression of these proteins in squamous cell carcinoma of the anterior tongue and compared their relationship with clinical stages and prognosis. Methods: Seventy-six patients with squamous cell carcinoma of the anterior tongue never treated before were obtained from Cancer Hospital, CAMS. Archive tissues of carcinoma and paracarcinoma were examined for c-erbB-2, p53 and p16 expression by immunohistochemistry. Results: The rates of immunopositive staining of c-erbB-2, p53 and p16 were 64.5%, 61.8% and 23.7% respectively; the positive rates in paracarcinoma mucosa were 19.7%, 22.6% and 55.3% respectively. Overexpression of c-erbB-2 was significantly correlated with short overall survival, metastasis and staging. Overexpression of paracarcinoma p53 was significantly correlated with local recurrence. Conclusion. c-erbB-2 may be used as a prognosis marker for the patients with squamous cell carcinoma of the anterior tongue and p53 as a recurrence marker.

Expression and Significance of IL-6 and bFGF in Human Tongue Squamous Cell Carcinoma

Objective: To detect the expression and pathological significances of Interleukin-6 (IL-6) and basic fibroblast growth factor (bFGF) in tongue squamous cell carcinoma (TSCC). Methods: A tissue array was analyzed immunohistochemically. The expression levels of IL-6 and bFGF in tissues were recorded semi-quantitatively. Results: The positive expression of IL-6 in normal, benign tumor, and carcinoma groups was 12.50% ± 5.575%, 39.00% ± 1.41%, 77.26% ± 17.07% respectively, and the expression among the three groups showed significant differences (P P P Conclusion: It indicates that combining immunohistochemical examination of IL-6 and bFGF has an important reference value on the pathological diagnosis of tongue squamous cell carcinoma.

KIF18A is a potential prognostic factor and promotes tumor progression in oral tongue squamous cell carcinoma

The kinesin family member 18A protein was dysregulated in several human cancers and involved in cancer progression.However,the significance in oral tongue squamous cell carcinoma(OTSCC)has not been studied.The present study was intended to explore the functions of KIF18A in oral tongue squamous cell carcinoma.The immunohistochemistry(IHC)assay was performed to assess the relationships between the KIF18A protein expression level and clinical-pathological features of the patients.The biological functions of KIF18A in OTSCC cells were investigated by the experiments in vitro and in vivo.Based on immunohistochemistry,we found that KIF18A was correlated with the clinical-pathological features of OTSCC patients.High expression of KIF18A was associated with the lymph node metastasis,and clinical stages.In vitro experiments revealed that silencing of KIF18A significantly inhibited the expression of the proliferation and migration related proteins such as Ki67,proliferating cell nuclear antigen,matrix metalloproteinase-7 and matrix metalloproteinase-9,and thereby inhibiting the proliferation,migration and invasion of tumor cells.In vivo,knocking-down of KIF18A could inhibit the tumor growth in nude mice.In conclusion,we found KIF18A promoted tumor progression in vivo and in vitro and might become an effective target for the treatment of OTSCC.

Inhibitory effect of celecoxib combined with cisplatin on growth of human tongue squamous carcinoma Tca8113 cell xenograft tumor

Objective:The aim of this study was to observe the inhibitory effect of application of COX-2 inhibitor,celecoxib,combined with cisplatin on the growth of human tongue squamous carcinoma Tca8113 cell xenograft by animal experiment.Methods:The nude mice were transplanted subcutaneously with Tca 8113 cells,and then were administrated with celecoxib,cisplatin or celecoxib combined with cisplatin respectively,and were sacrificed after 35 days.The weight of xenograft was measured to calculate the tumor inhibition rate.The histological change was studied under light and electron microscope.The COX-2 protein expression was observed by immunohistological staining.And the COX-2 mRNA expression was determined by RT-PCR.Results:Celecoxib,the COX-2 inhibitor,could not only inhibit the growth of Tca8113 cell xenograft tumor and COX-2 protein expression,but also enhance the inhibitory effect cisplatin on xenograft tumor growth significantly.The tumor inhibition rates of celecoxib group,cisplatin group and celecoxib plus cisplatin group were 15.63%,37.50% and 82.81% respectively that was statistically significant compared to control group(P < 0.01).The combined application of celecoxib and cisplatin could inhibit tumor growth more significantly than that of separated application(P < 0.01).The inhibitory effect of celecoxib on COX-2 mRNA expression of Tca 8113 cell was weaker and not significant(P = 0.073).Conclusion:Celecoxib can not only inhibit xenograft tumor growth in nude mice,but also enhance the inhibitory effect of CDDP on Tca 8113 transplanted tumor growth in nude mice.The mechanism maybe related to inhibition of COX-2 protein expression,which offers beneficial reference to further explore the mechanism between inhibition of COX-2 enzyme activity and prevention of head and neck tumor.

Development and validation of novel nomograms to predict survival of patients with tongue squamous cell carcinoma

BACKGROUND There is no unified standard to predict postoperative survival in patients with tongue squamous cell carcinoma(TSCC),hence the urgency to develop a model to accurately predict the prognosis of these patients.AIM To develop and validate nomograms for predicting overall survival(OS)and cancer-specific survival(CSS)of patients with TSCC.METHODS A cohort of 3454 patients with TSCC from the Surveillance,Epidemiology,and End Results(SEER)database was used to develop nomograms;another independent cohort of 203 patients with TSCC from the Department of Oral and Maxillofacial Surgery,First Affiliated Hospital of Zhejiang University School of Medicine,was used for external validation.Univariate and multivariate analyses were performed to identify useful variables for the development of nomograms.The calibration curve,area under the receiver operating characteristic curve(AUC)analysis,concordance index(C-index),net reclassification index(NRI),and decision curve analysis(DCA)were used to assess the calibration,discrimination ability,and clinical utility of the nomograms.RESULTS Eight variables were selected and used to develop nomograms for patients with TSCC.The Cindex(0.741 and 0.757 for OS and CSS in the training cohort and 0.800 and 0.830 in the validation cohort,respectively)and AUC indicated that the discrimination abilities of these nomograms were acceptable.The calibration curves of OS and CSS indicated that the predicted and actual values were consistent in both the training and validation cohorts.The NRI values(training cohort:0.493 and 0.482 for 3-and 5-year OS and 0.424 and 0.402 for 3-and 5-year CSS;validation cohort:0.635 and 0.750 for 3-and 5-year OS and 0.354 and 0.608 for 3-and 5-year CSS,respectively)and DCA results indicated that the nomograms were significantly better than the tumor-node-metastasis staging system in predicting the prognosis of patients with TSCC.CONCLUSION Our nomograms can accurately predict patient prognoses and assist clinicians in improving decision-making concerning patients with TSCC in clinical practice.

miR-23a Promoting Cell Proliferation of Human Tongue Squamous Cell Carcinoma Cell through Regulating PPP2R5E

[Objectives]To investigate the mechanism of miR-23a in the proliferation of human tongue squamous cell carcinoma cells.[Methods]Clinical tissue samples of tongue squamous cell carcinoma were collected and Tca8113 and CAL27 were cultured.Real-time quantitative PCR was performed to detect the expressions of miR-23a and PPP2R5E in clinical tissue samples of tongue squamous cell carcinoma.MTT assay,colony formation assay and growth curve assay were used to detect the effect of miR-23a and PPP2R5E on the proliferation of human tongue squamous carcinoma cell.Luciferase reporter assay verified the regulatory relationship between miR-23a and PPP2R5E.[Results]The expression of miR-23a in tongue squamous cell carcinoma was significantly up-regulated(P<0.01).miR-23a promoted the proliferation of tongue squamous cell carcinoma cells.Bioinformatics prediction and luciferin reporting experiments showed that PPP2R5E was a direct target gene of miR-23a.The expression of PPP2R5E was decreased in tongue squamous cell carcinoma.PPP2R5E inhibited the proliferation of tongue squamous cell carcinoma cells.Overexpression of PPP2R5E can reverse the proliferation promoting effect of miR-23a on tongue squamous cell carcinoma cells.[Conclusions]miR-23a can promote the proliferation of tongue squamous cell carcinoma cells through PPP2R5E and miR-23a plays an oncogene role in the occurrence and development of tongue squamous cell carcinoma.

Excision margins in squamous cell carcinoma of the tongue: A retrospective audit and review of the literature

The incidence of close and involved tongue resection margins for squamous cell carcinoma (SCC) were reviewed with the aim to identify any possible need for change in the surgical approach to glossectomies. The histopathological reports of 101 partial glossectomies for SCC between 2006 and 2012 were retrospectively reviewed. Results: Overall 52 (51.5%) patients had one or more close or involved margin and 9 (8.9%) had both close and involved margins. 42 (41.5%) patients had close margins and 11 (10.9%) had involved margins. The inferior/lateral muscoal margin was most frequently close/involved (32%) followed by deep margin (27%). The anterior margin was least close/involved (5%). The posterior and superior/medical margins were close/involved in 12% and 11% of cases respectively. Conclusions: 52.5% of patients had close or involved margins following surgery, potentially requiring further treatment to avoid an increased risk of tumour recurrence and the associated increase in morbidity and mortality. The inferior/lateral and deep margins were most frequently involved possible due to the anatomical difficulties visualising and dissecting these margins. The potential explanations for these disparities and possible solutions are discussed.

Multiple distant metastasis of tongue squamous cell carcinoma after surgical operation and radiotherapy——a case report and literature review

This article reported a 36-year male patient with tongue squamous cell carcinoma who showed negative cervical lymphadenopathy by clinical examination but cervical lymph node metastases diagnosed by pathological examination. The patient underwent tongue tumor resection and left forearm radial skin flap repair, and then received 50 Gy 3-D conformal radiotherapy and chemotherapy combining 5-fluorouracil with carboplatin. One year after the operation, although the patient showed no tumor recurrence in primary site and no metastasis of cervical lymph nodes, metastasis occurred in several tissues including spine, ribs, mandible, skeletal muscles of upper extremity as well as lymph nodes of the mediastinum and lung hilum, which caused the patient to die quickly. According to the literature, we conclude that distant metastasis of tongue squamous cell carcinoma was less common, but once it occurs, the prognosis of the patient is extremely poor.

Effects of hsa-circ-0001862 on Phenotype of Tongue Squamous Cell Carcinoma Cells

[Objectives]To investigate the molecular mechanism of hsa_circ_0001862 on the proliferation,migration,invasion and apoptosis of tongue squamous cell carcinoma Tca-8113 cells.[Methods]hsa_circ_0001862 plasmid was constructed,and the interaction relationship between hsa_circ_0001862 and miR-23a-3p was verified by dual luciferase reporter gene and qRT-PCR.CCK8 assay,colony formation assay,scratch assay and Transwell assay were used to detect the proliferation,migration and invasion ability of Tca-8113 cells.Western blot was used to detect the expression level of apoptosis-related protein molecules.The effects of hsa_circ_0001862 on the apoptosis of Tca-8113 cells was detected.[Results]hsa_circ_0001862 and miR-23a-3p could interact,and their expression was negatively correlated in tongue squamous cell carcinoma cells.In Tca-8113 cells,hsa_circ_0001862 inhibited cell proliferation,migration,and invasion(P<0.01),and promoted cell apoptosis(P<0.01).[Conclusions]The hsa_circ_0001862 interacts with miR-23a-3p,and hsa_circ_0001862 plays an inhibitory role in the development of tongue squamous cell carcinoma.The hsa_circ_0001862 may be a new biomarker and target for the treatment of tongue squamous cell carcinoma.

Effects of lentinan and thymopentin combined with adjuvant chemotherapy on immunity, oxidative stress, matrix metalloproteinases and related factors in patients with tongue squamous cell carcinoma

Objective:To investigate the effects of lentinan and thymopentin combined with adjuvant chemotherapy on immunity, oxidative stress, matrix metalloproteinases and related factors in patients with tongue squamous cell carcinoma.Methods: Retrospective analysis of 78 patients with tongue squamous cell carcinoma admitted to our hospital from February 2013 to November 2017, according to the postoperative chemotherapy scheme, the patients were divided into control group (n=42) and observation group (n=36). The patients in control group were given PF chemotherapy scheme (cisplatin + compound fluorouracil injection), on this basis, the patients in observation group were given lentinan and thymopentin injection combined treatment. The immune index, oxidative stress, matrix metalloproteinase, cyclin D1 (CyclinD1) and B lymphocyte tumor-2 (BCL-2) were detected and analyzed before and after treatment.Results:After treatment, the immunoglobulin level in the control group was not statistically significant compared with that before treatment (P>0.05);the levels of IgA, IgG and IgM in the observation group were significantly higher than those before treatment (P<0.05), and the levels of IgA, IgG and IgM in the observation group were significantly higher than those in the control group (P<0.05);the level of SOD in control group was significantly lower than that before treatment (P<0.05), and the level of MDA was significantly higher than that before treatment (P<0.05);the observation group was the opposite, and its SOD level was significantly higher than that of the control group (P<0.05), and the MDA level was significantly lower than the control group (P<0.05);the levels of MMP-2 and MMP-9 in the two groups were significantly lower than those before treatment (P<0.05), and the levels of MMP-2 and MMP-9 in the observation group were significantly lower than those in the control group (P<0.05);the levels of CyclinD1 and BCL-2 in the two groups were significantly lower than those before treatment (P<0.05), and the levels of CyclinD1 and BCL-2 in the observation group were significantly lower than those in the control group (P<0.05).Conclusions:Lentinan and thymopentin assisted PF chemotherapy regimen can enhance the immune function of patients with tongue squamous cell carcinoma after radical surgery, improve oxidative stress response, inhibit tumor cell proliferation and metastasis. It has the significance of clinical popularization.

Sternocleidomastoid flap for reconstruction of tongue small cell carcinoma: A case report

BACKGROUND The management of tongue carcinoma is excision and radical neck dissection followed with reconstruction.This is a case report of a patient with tongue squamous cell carcinoma(SCC)who underwent the procedure with sternocleidomastoid(SCM)flap reconstruction.CASE SUMMARY A 52-year-old woman without smoking history complained tongue ulcer since 3 years ago.Based on the histopathological examination,the patient was diagnosed with T2N2M0 right tongue SCC and underwent wide excision of tumor;right mandibular;neck dissection and were reconstructed with SCM flap.CONCLUSION SCC of the tongue requires wide excision and dissection of the neck and mandible if infiltration into the surrounding lymph nodes has been found.The SCM flap reconstruction could be used post-surgery.

Relationship between COX-2 and cell cycle-regulatory proteins in patients with esophageal squamous cell carcinoma

AIM: To investigate the correlation between cyclooxygenase-2 (COX-2) and cell cycle-regulatory proteins in patients with esophageal squamous cell carcinoma (ESCC). METHODS: One hundred and two surgically obtained specimens of ESCC were randomly collected. All specimens were obtained from patients who had not received chemoor radiotherapy prior to surgical resection.Twenty-eight specimens of normal squamous epithelium served as controls. The expression of COX-2, Ki-67, cyclin A and p27 was examined by immunohistochemistry. The Pearson test was used to analyze the relationship between groups. RESULTS: The protein level of COX-2, Ki-67 and cyclin A was significantly higher in ESCC than in normal squamous epithelium (74.7±61.2 vs 30.2 ± 43.4, 64.0 ± 51.6 vs 11.6 ± 2.3, 44.2 ± 32.2 vs 11.7 ± 5.0, respectively, all P<0.01). In contrast, the protein level of p27 was signifi cantly lower in ESCC than in normal squamous epithelium (182.0 ±69.0 vs 266.4±28.0, P<0.01). In ESCC, COX-2 expression was correlated with T stage, the score of T1-T2 stage was lower than that of T3-T4 stage (55.0±42.3 vs 83.0 ± 66.5, P<0.05), and Ki-67, cyclin A and p27 expressions were correlated with the tumor differentiation (43.8±31.7 vs 98.4± 84.8, 32.0 ± 19.0 vs 54.1 ±53.7,206.2±61.5 vs 123.5±68.3, respectively, all P<0.01). COX-2 expression was positively correlated to Ki-67, cyclin A and negatively correlated to p27 expression in ESCC (r=0.270, 0.233 and-0.311, respectively, all P<0.05).CONCLUSION: The expression of COX-2 is correlated with tumor cell invasion and is closely related to the cell proliferation in patients with ESCC.