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.

CES1 is associated with cisplatin resistance and poor prognosis of head and neck squamous cell carcinoma

Background:Head and neck squamous cell carcinoma(HNSCC)is a prevalent form of cancer globally,with chemoresistance posing a major challenge in treatment outcomes.The efficacy of the commonly used chemotherapeutic agent,cisplatin,is diminished in patients with poor prognoses.Methods:Various bioinformatics databases were utilized to examine Carboxylesterase 1(CES1)gene expression,clinicopathologic features,patient survival analysis,and gene function.An organoid model of HNSCC was established,along with the induction of drug-resistant HNSCC in the organoid model.CES1 expression was assessed using qRT-PCR and Western Blot,and differential markers were identified through transcriptome sequencing.Knockdown and overexpression models of CES1 were created in SCC-9 and patient-derived organoid(PDO)cells using shRNA and lentivirus to investigate the tumor biology and cisplatin resistance associated with CES1.Results:Research in bioinformatics has uncovered a strong correlation between the expression level of CES1 and the prognosis of HNSCC.The data suggests a significant link between CES1 expression and tobacco smoking.RNA-sequencing revealed a notable increase in CES1 expression in HNSCC-PDOcis-R cells compared to the parental PDO cells.Subsequently,we performed in vitro studies by HNSCC-PDO and SCC-9 and found that CES1-overexpressing cells exhibited reduced sensitivity to cisplatin and stronger tumor malignant biological behavior compared with CES1-knockdown cells.Conclusion:The observed association between CES1 expression and tobacco smoking implies a potential influence of smoking on the efficacy of cisplatin-based chemotherapy in HNSCC through the regulation of CES1 expression.

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.

Fibroblast activation protein (FAP) as a prognostic biomarker in multiple tumors and its therapeutic potential in head and neck squamous cell carcinoma

Background:Fibroblast activation protein(FAP),a cell surface serine protease,plays roles in tumor invasion and immune regulation.However,there is currently no pan-cancer analysis of FAP.Objective:We aimed to assess the pan-cancer expression profile of FAP,its molecular function,and its potential role in head and neck squamous cell carcinoma(HNSC).Methods:We analyzed gene expression,survival status,immune infiltration,and molecular functional pathways of FAP in The Cancer Genome Atlas(TCGA)and Genotype Tissue Expression(GTEx)tumors.Furthermore,to elucidate the role of FAP in HNSC,we performed proliferation,migration,and invasion assays post-FAP overexpression or knock-down.Results:FAP expression was elevated in nine tumor types and was associated with poor survival in eight of them.In the context of immune infiltration,FAP expression negatively correlated with CD8+T-cell infiltration infive tumor types and positively with regulatory T-cell infiltration in four tumor types.Our enrichment analysis highlighted FAP’s involvement in the PI3K-Akt signaling pathway.In HNSC cells,FAP overexpression activated the PI3K-Akt pathway,promoting tumor proliferation,migration,and invasion.Conversely,FAP knockdown showed inhibitory effects.Conclusion:Our study unveils the association of FAP with poor tumor prognosis across multiple cancers and highlights its potential as a therapeutic target in HNSC.

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.

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.

Novel defined N7-methylguanosine modification-related lncRNAs for predicting the prognosis of laryngeal squamous cell carcinoma

Objective:Through integrated bioinformatics analysis,the goal of this work was to find new,characterised N7-methylguanosine modification-related long non-coding RNAs(m7G-lncRNAs)that might be used to predict the prognosis of laryngeal squamous cell carcinoma(LSCC).Methods:The clinical data and LSCC gene expression data for the current investigation were initially retrieved from the TCGA database&sanitised.Then,using co-expression analysis of m7G-associated mRNAs&lncRNAs&differential expression analysis(DEA)among LSCC&normal sample categories,we discovered lncRNAs that were connected to m7G.The prognosis prediction model was built for the training category using univariate&multivariate COX regression&LASSO regression analyses,&the model’s efficacy was checked against the test category data.In addition,we conducted DEA of prognostic m7G-lncRNAs among LSCC&normal sample categories&compiled a list of co-expression networks&the structure of prognosis m7G-lncRNAs.To compare the prognoses for individuals with LSCC in the high-&low-risk categories in the prognosis prediction model,survival and risk assessments were also carried out.Finally,we created a nomogram to accurately forecast the outcomes of LSCC patients&created receiver operating characteristic(ROC)curves to assess the prognosis prediction model’s predictive capability.Results:Using co-expression network analysis&differential expression analysis,we discovered 774 m7G-lncRNAs and 551 DEm7G-lncRNAs,respectively.We then constructed a prognosis prediction model for six m7G-lncRNAs(FLG−AS1,RHOA−IT1,AC020913.3,AC027307.2,AC010973.2 and AC010789.1),identified 32 DEPm7G-lncRNAs,analyzed the correlation between 32 DEPm7G-lncRNAs and 13 DEPm7G-mRNAs,and performed survival analyses and risk analyses of the prognosis prediction model to assess the prognostic performance of LSCC patients.By displaying ROC curves and a nomogram,we finally checked the prognosis prediction model's accuracy.Conclusion:By creating novel predictive lncRNA signatures for clinical diagnosis&therapy,our findings will contribute to understanding the pathogenetic process of LSCC.

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.

Metabolic syndrome is associated with better prognosis in patients with tongue squamous cell carcinoma

Introduction:Metabolic syndrome(MS) is associated with several cancers,but it is not clear whether MS affects the prognosis of tongue squamous cell carcinoma(TSCC).This study aimed to evaluate the prognostic value of MS in TSCC.Methods:Clinical data from 252 patients with TSCC who were initially treated at the Sun Yat-sen University Cancer Center between April 1998 and June 2011 were collected,and the associations between MS and ciinicopathologic factors were retrospectively analyzed.Prognostic outcomes were examined by Kaplan-Meier analysis and Cox regression analysis.Results:Of the 252 patients,48 were diagnosed with MS.MS was associated with early N category in TSCC[P< 0.001).The patients with MS showed longer survival than those without MS(P = 0.028).MS was an independent prognostic factor for patients with TSCC Conclusions:MS is associated with early N category in TSCC.It is an independent prognostic factor for better survival in patients with TSCC.

Different types of tumor microvessels in stageⅠ-ⅢA squamous cell lung cancer and their clinical significance

BACKGROUND Lung cancer(LC)is the leading cause of morbidity and mortality among malignant neoplasms.Improving the diagnosis and treatment of LC remains an urgent task of modern oncology.Previously,we established that in gastric,breast and cervical cancer,tumor microvessels(MVs)differ in morphology and have different prognostic significance.The connection between different types of tumor MVs and the progression of LC is not well understood.AIM To evaluate the morphological features and clinical significance of tumor MVs in lung squamous cell carcinoma(LUSC).METHODS A single-center retrospective cohort study examined medical records and archival paraffin blocks of 62 and 180 patients with stage I-IIIA LUSC in the training and main cohorts,respectively.All patients underwent radical surgery(R0)at the Orenburg Regional Cancer Clinic from May/20/2009 to December/14/2021.Tumor sections were routinely processed,and routine Mayer's hematoxylin and eosin staining and immunohistochemical staining for cluster of differentiation 34(CD34),podoplanin,Snail and hypoxia-inducible factor-1 alpha were performed.The morphological features of different types of tumor MVs,tumor parenchyma and stroma were studied according to clinicopathological characteristics and LUSC prognosis.Statistical analysis was performed using Statistica 10.0 software.Univariate and multivariate logistic regression analyses were performed to identify potential risk factors for LUSC metastasis to regional lymph nodes(RLNs)and disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with and without metastases in RLNs and those with and without disease recurrence.The effectiveness of the predictive models was assessed by the area under the curve.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.A value of P<0.05 was considered to indicate statistical significance.RESULTS Depending on the morphology,we classified tumor vessels into the following types:normal MVs,dilated capillaries(DCs),atypical DCs,DCs with weak expression of CD34,"contact-type"DCs,structures with partial endothelial linings,capillaries in the tumor solid component and lymphatic vessels in lymphoid and polymorphocellular infiltrates.We also evaluated the presence of loose,fine fibrous connective tissue(LFFCT)and retraction clefts in the tumor stroma,tumor spread into the alveolar air spaces(AASs)and fragmentation of the tumor solid component.According to multivariate analysis,the independent predictors of LUSC metastasis in RLNs were central tumor location(P<0.00001),the presence of retraction clefts(P=0.003),capillaries in the tumor solid component(P=0.023)and fragmentation in the tumor solid component(P=0.009),whereas the independent predictors of LUSC recurrence were tumor grade 3(G3)(P=0.001),stage N2(P=0.016),the presence of LFFCT in the tumor stroma(P<0.00001),fragmentation of the tumor solid component(P=0.0001),and the absence of tumor spread through the AASs(P=0.0083).CONCLUSION The results obtained confirm the correctness of our previously proposed classification of different types of tumor vessels and may contribute to improving the diagnosis and treatment of LUSC.

Comprehensive bioinformatics analysis and experimental validation:An anoikis-related gene prognostic model for targeted drug development in head and neck squamous cell carcinoma

We analyzed RNA-sequencing(RNA-seq)and clinical data from head and neck squamous cell carcinoma(HNSCC)patients in The Cancer Genome Atlas(TCGA)Genomic Data Commons(GDC)portal to investigate the prognostic value of anoikis-related genes(ARGs)in HNSCC and develop new targeted drugs.Differentially expressed ARGs were screened using bioinformatics methods;subsequently,a prognostic model including three ARGs(CDKN2A,BIRC5,and PLAU)was constructed.Our results showed that the model-based risk score was a good prognostic indicator,and the potential of the three ARGs in HNSCC prognosis was validated by the TISCH database,the model’s accuracy was validated in two independent cohorts of the Gene Expression Omnibus database.Immune correlation analysis and half-maximal inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to predict immuno-and chemo-therapeutic responses.Potential small-molecule drugs for HNSCC were subsequently predicted using the L1000FWD database.Finally,in vitro experiments were used to verify the database findings.The relative ARG mRNA expression levels in HNSCC and surrounding normal tissues remained consistent with the model results.BIRC5 knockdown inhibited anoikis resistance in WSU-HN6 and CAL-27 cells.Molecular docking,real-time PCR,cell counting kit-8(CCK-8),plate clone,and flow cytometry analyses showed that small-molecule drugs predicted by the database may target the ARGs in the prognostic model,inhibit HNSCC cells survival rate,and promote anoikis in vitro.Therefore,we constructed a new ARG model for HNSCC patients that can predict prognosis and immune activity and identify a potential small-molecule drug for HNSCC,paving the way for clinically targeting anoikis in HNSCC.

Identification of a three-gene prognostic signature for radioresistant esophageal squamous cell carcinoma

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is causing a high mortality rate due to the lack of efficient early prognosis markers and suitable therapeutic regimens.The prognostic role of genes responsible for the acquisition of radioresistance in ESCC has not been fully elucidated.AIM To establish a prognostic model by studying gene expression patterns pertinent to radioresistance in ESCC patients.METHODS Datasets were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases.The edgeR,a Bioconductor package,was used to analyze mRNA expression between different groups.We screened genes specifically responsible for radioresistance to estimate overall survival.Pearson correlation analysis was performed to confirm whether the expression of those genes correlated with each other.Genes contributing to radioresistance and overall survival were assessed by the multivariate Cox regression model through the calculation ofβi and risk score using the following formula:∑^(n)_(i=1)βi×PSI.RESULTS We identified three prognostic mRNAs(cathepsin S[CTSS],cluster of differentiation 180[CD180],and SLP adapter and CSK-interacting membrane protein[SCIMP])indicative of radioresistance.The expression of the three identified mRNAs was related to each other(r>0.70 and P<0.05).As to 1-year and 3-year overall survival prediction,the area under the time-dependent receiver operating characteristic curve of the signature consisting of the three mRNAs was 0.716 and 0.841,respectively.When stratifying patients based on the risk score derived from the signature,the high-risk group exhibited a higher death risk and shorter survival time than the low-risk group(P<0.0001).Overall survival of the low-risk patients was significantly better than that of the highrisk patients(P=0.018).CONCLUSION We have developed a novel three-gene prognostic signature consisting of CTSS,CD180,and SCIMO for ESCC,which may facilitate the prediction of early prognosis of this malignancy.

Co-existing squamous cell carcinoma and chronic myelomonocytic leukemia with ASXL1 and EZH2 gene mutations:A case report

BACKGROUND Chronic myelomonocytic leukemia(CMML),a rare clonal hematopoietic stem cell disorder characterized by myelodysplastic syndrome and myeloproliferative neoplasms,has a generally poor prognosis,and easily progresses to acute myeloid leukemia.The simultaneous incidence of hematologic malignancies and solid tumors is extremely low,and CMML coinciding with lung malignancies is even rarer.Here,we report a case of CMML,with ASXL1 and EZH2 gene mutations,combined with non-small cell lung cancer(lung squamous cell carcinoma).CASE SUMMARY A 63-year-old male,suffering from toothache accompanied by coughing,sputum,and bloody sputum for three months,was given a blood test after experiencing continuous bleeding resulting from a tooth extraction at a local hospital.Based on morphological results,the patient was diagnosed with CMML and bronchoscopy was performed in situ to confirm the diagnosis of squamous cell carcinoma in the lower lobe of the lung.After receiving azacitidine,programmed cell death protein 1,and platinum-based chemotherapy drugs,the patient developed severe myelosuppression and eventually fatal leukocyte stasis and dyspnea.CONCLUSION During the treatment and observation of CMML and be vigilant of the growth of multiple primary malignant tumors.

Correlation of plasma miR-21 and miR-93 with radiotherapy and chemotherapy efficacy and prognosis in patients with esophageal squamous cell carcinoma

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the main causes of human death.It is usually already in middle or advanced stage when diagnosed due to its hidden symptoms in early stage.Therefore,patients have already lost the best surgical timing when diagnosed.Radiotherapy and chemotherapy are standard treatment methods for ESCC clinically,but the efficacy and prognosis of patients from them are still unsatisfactory.Therefore,it is of great clinical significance to seek for biomarkers that can predict the radiotherapy and chemotherapy response and prognosis of ESCC patients.AIM To explore the clinical value of plasma miR-21 and miR-93 in ESCC.METHODS A total of 128 ESCC patients admitted to the First Affiliated Hospital of Zhenzhou University were enrolled as a study group and treated with concurrent radiotherapy and chemotherapy,and other 45 healthy people during the same period were enrolled as a control group.The expression of plasma miR-21 and miR-93 was determined using quantitative real-time polymerase chain reaction,and the correlation of expression of plasma miR-21 and miR-93 with clinical pathological parameters about the patients was analyzed.The receiver operating characteristic(ROC)curve was adopted to assess the diagnostic value of plasma miR-21 and miR-93 for clinical pathological features of ESCC patients,the Logistic regression analysis adopted to analyze the risk factors for radiotherapy and chemotherapy efficacy in ESCC patients,and the Cox regression analysis to identify the prognostic factors for ESCC patients.RESULTS The study group showed significantly higher relative expression of plasma miR-21 and miR-93 than the control group(P<0.01).The area under the ROC curve(AUC)of plasma miR-21 for diagnosing T stage,N stage,M stage,and pathological differentiation of ESCC was 0.819,0.758,0.824,and 0.725,respectively,and that of plasma miR-93 for diagnosing T stage,N stage,and M stage of ESCC was 0.827,0.815,and 0.814,respectively.The AUC of combined plasma miR-21 and miR-93 for predicting radiotherapy and chemotherapy efficacy before radiotherapy and chemotherapy was 0.894,and the AUCs of them for predicting the 3-year overall survival(OS)were 0.861 and 0.807,respectively.T stage(P<0.05),M stage(P<0.05),miR-21(P<0.01),and miR-93(P<0.05)were independent risk factors for radiotherapy and chemotherapy efficacy,and T stage(P<0.01),N stage(P<0.05),M stage(P<0.01),miR-21(P<0.01),and miR-93(P<0.01)were independent prognostic factors for ESCC patients.CONCLUSION MiR-21 and miR-93 can be adopted as effective biomarkers for predicting radiotherapy and chemotherapy efficacy in ESCC and the 3-year OS of ESCC patients.

Vasculogenic Mimicry and Aberrant Expression of HIF-lα/E-cad Are Associated with Worse Prognosis of Esophageal Squamous Cell Carcinoma

Summary： This study aims to find good markers for predicting the prognosis of patients with eso- phageal squamous cell carcinoma （ESCC）. Vasculogenic mimicry （VM） and the expression of hy- poxia inducible factor-1α（HIF-1α）/E-cad protein in ESCC were investigated by immunostaining. The association between VM, HIF-1α/E-cad and clinicopathologic characteristics and 5-year-survival rate of patients with ESCC was analyzed. A total of 160 ESCC specimens were involved in this study and 28 specimens of normal esophageal mucosa served as controls. VM channels were identified in 78 （48.75%） of the 160 ESCC specimens and none of the normal esophageal mucosa was found to have VM. The rates of high-expression of HIF-1αand E-cad in ESCC were 43.75% and 38.75%, while the rates in control were 17.86% and 71.43%, respectively （P〈0.05 for all）. VM and the expression levels of HIF-1α and E-cad were significantly related to lymph node metastasis, serosa infiltration, PTNM staging and 5-year-survival rates of patients with ESCC （P〈0.05 for all）. VM was positively corre- lated with HIF-1α but negatively with E-cad, and HIF-let was negatively correlated with E-cad （P〈0.001 for all）. The 5-year-survival rate of patients with ESCC was 6.41% （5/78） in VM group and 65% （52/82） in non-VM group, 7.14% （5/70） in high HIF-1α expression group and 57.78% （52/90） in low HIF-1α expression group. Oppositely, the 5-year-survival rate in high E-cad expression group was 80.65% （50/62） and that in low E-cad expression group was 7.37% （7/98） （P〈0.05 for all）. Cox multifactor regression analysis indicated that lymph node metastasis, PTNM stage, VM and expres- sion levels of HIF-1α and E-cad were independent risk factors of patients with ESCC （P〈0.05 for all）. Combined detection ofVM, HIF-1α and E-cad plays an important role in predicting the invasion, me- tastasis and prognosis of patients with ESCC.

Significance of preoperative C-reactive protein as a parameter of the perioperative course and long-term prognosis in squamous cell carcinoma and adenocarcinoma of the oesophagus

AIM： C-reactive protein （CRP） is an acute-phase reactant and a known indicator of the malignant potential of the tumour. The aim of this study was to investigate the significance of preoperative CRP as a parameter of the perioperative course and long-term prognosis in patients with squamous cell carcinoma and aclenocarcinoma of the oesophagus. METHODS： Serum CRP was determined preoperatively in 291 of 371 patients undergoing oesophagectomy for cancer from December 1989 to March 2004. Median patient age was 59 （28-79） year, 82.5% of patients were males. Squamous cell carcinoma was diagnosed in 151 （51.9%） and aclenocarcinoma in 122 patients. Transhiatal oesophagectomy was clone in 151 （51.9%） patients and 134 （46.0%） patients underwent the abclominothoracic procedure. RESULTS： In 127 （43.6%） patients the preoperative serum CRP concentration was within the normal range （〈 5 mg/clL）, elevated CRP levels were measured in 164 （56.4%） patients. Tumour extension （P 〈 0.0005） and the number of lymph nodes affected by metastatic spread （P = 0.015） were significantly increased in the group with elevated CRP levels. Among the perioperative parameters both the number of blood transfusions （P = 0.006） and the general complication rate （P = 0.002） were higher in patients with elevated preoperative CRP levels. The long-term survival rate of 13.6 （0-109.8） mo was poorer in the group with elevated CRP levels compared to 18.9 （0-155.4） mo in the group with normal CRP levels （log-rank test： P = 0.107）. Multivariateanalysis with backward variables selection identified preoperative CRP as an independent prognostic factor of the long-term prognosis in patients with oesophageal carcinoma, with a hazard ratio of 1.182 （95% confidence interval： 1.030-1.356）. CONCLUSION： The preoperative serum CRP-level is an easily determined independent prognostic marker in patients with squamous cell carcinoma and adenocarcinoma of the oesophagus.

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.

Genetic Variants in EGFR/PLCE1 Pathway Are Associated with Prognosis of Esophageal Squamous Cell Carcinoma after Radical Resection

Esophageal cancer (EC) is one of the most deadly malignant diseases. Several studies revealed that variations of the phospholipase C epsilon 1 (PLCE1) gene were associated with EC susceptibility. PLCE1 is located downstream of the epidermal growth factor receptor (EGFR) pathway. Presently, the single nucleotide polymorphisms (SNPs) of EGFR/PLCE1 genes and their associations with EC survival remain unclea匚 In this study, the associations between genetic variants in the EGFR/PLCE1 pathway and prognosis in 124 esophageal squamous cell carcinoma (ESCC) patients with radical resection were explored. The results showed that CC genotype of both PLCE1 rsl7109671 and EGFR rs2072454 was associated with ESCC prognosis. Multivariate analysis revealed that patients with the two unfavorable genotypes had the worst overall survival (OS) or disease-free survival (DFS)(HR=6.099, 95%CI=1.903-19.552;HR=3.994, 95%CI=1.49-10.702, respectively). Additionally, combination of SNPs and tumor stage could better predict OS (for AUC, 0.774 vs. 0.709) and PFS (for AUC, 0.773 vs. 0.704) than tumor stage alone.In conclusion, genetic variants of the EGFR/PLCE1 may be predictors of the prognosis of ESCC after surgery. The individuals with the CC genotype of PLCE1 rsl7109671 and EGFR rs2072454 should receive more aggressive treatments.

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.