Preoperative prediction of lymphovascular and perineural invasion in gastric cancer using spectral computed tomography imaging and machine learning

BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are important prognostic factors for gastric cancer(GC)that indicate an increased risk of metastasis and poor outcomes.Accurate preoperative prediction of LVI/PNI status could help clinicians identify high-risk patients and guide treatment deci-sions.However,prior models using conventional computed tomography(CT)images to predict LVI or PNI separately have had limited accuracy.Spectral CT provides quantitative enhancement parameters that may better capture tumor invasion.We hypothesized that a predictive model combining clinical and spectral CT parameters would accurately preoperatively predict LVI/PNI status in GC patients.AIM To develop and test a machine learning model that fuses spectral CT parameters and clinical indicators to predict LVI/PNI status accurately.METHODS This study used a retrospective dataset involving 257 GC patients(training cohort,n=172;validation cohort,n=85).First,several clinical indicators,including serum tumor markers,CT-TN stages and CT-detected extramural vein invasion(CT-EMVI),were extracted,as were quantitative spectral CT parameters from the delineated tumor regions.Next,a two-step feature selection approach using correlation-based methods and information gain ranking inside a 10-fold cross-validation loop was utilized to select informative clinical and spectral CT parameters.A logistic regression(LR)-based nomogram model was subsequently constructed to predict LVI/PNI status,and its performance was evaluated using the area under the receiver operating characteristic curve(AUC).RESULTS In both the training and validation cohorts,CT T3-4 stage,CT-N positive status,and CT-EMVI positive status are more prevalent in the LVI/PNI-positive group and these differences are statistically significant(P<0.05).LR analysis of the training group showed preoperative CT-T stage,CT-EMVI,single-energy CT values of 70 keV of venous phase(VP-70 keV),and the ratio of standardized iodine concentration of equilibrium phase(EP-NIC)were independent influencing factors.The AUCs of VP-70 keV and EP-NIC were 0.888 and 0.824,respectively,which were slightly greater than those of CT-T and CT-EMVI(AUC=0.793,0.762).The nomogram combining CT-T stage,CT-EMVI,VP-70 keV and EP-NIC yielded AUCs of 0.918(0.866-0.954)and 0.874(0.784-0.936)in the training and validation cohorts,which are significantly higher than using each of single independent factors(P<0.05).CONCLUSION The study found that using portal venous and EP spectral CT parameters allows effective preoperative detection of LVI/PNI in GC,with accuracy boosted by integrating clinical markers.

Preoperative prediction of perineural invasion of rectal cancer based on a magnetic resonance imaging radiomics model:A dual-center study

BACKGROUND Perineural invasion(PNI)has been used as an important pathological indicator and independent prognostic factor for patients with rectal cancer(RC).Preoperative prediction of PNI status is helpful for individualized treatment of RC.Recently,several radiomics studies have been used to predict the PNI status in RC,demonstrating a good predictive effect,but the results lacked generalizability.The preoperative prediction of PNI status is still challenging and needs further study.AIM To establish and validate an optimal radiomics model for predicting PNI status preoperatively in RC patients.METHODS This retrospective study enrolled 244 postoperative patients with pathologically confirmed RC from two independent centers.The patients underwent preoperative high-resolution magnetic resonance imaging(MRI)between May 2019 and August 2022.Quantitative radiomics features were extracted and selected from oblique axial T2-weighted imaging(T2WI)and contrast-enhanced T1WI(T1CE)sequences.The radiomics signatures were constructed using logistic regression analysis and the predictive potential of various sequences was compared(T2WI,T1CE and T2WI+T1CE fusion sequences).A clinical-radiomics(CR)model was established by combining the radiomics features and clinical risk factors.The internal and external validation groups were used to validate the proposed models.The area under the receiver operating characteristic curve(AUC),DeLong test,net reclassification improvement(NRI),integrated discrimination improvement(IDI),calibration curve,and decision curve analysis(DCA)were used to evaluate the model performance.RESULTS Among the radiomics models,the T2WI+T1CE fusion sequences model showed the best predictive performance,in the training and internal validation groups,the AUCs of the fusion sequence model were 0.839[95%confidence interval(CI):0.757-0.921]and 0.787(95%CI:0.650-0.923),which were higher than those of the T2WI and T1CE sequence models.The CR model constructed by combining clinical risk factors had the best predictive performance.In the training and internal and external validation groups,the AUCs of the CR model were 0.889(95%CI:0.824-0.954),0.889(95%CI:0.803-0.976)and 0.894(95%CI:0.814-0.974).Delong test,NRI,and IDI showed that the CR model had significant differences from other models(P<0.05).Calibration curves demonstrated good agreement,and DCA revealed significant benefits of the CR model.CONCLUSION The CR model based on preoperative MRI radiomics features and clinical risk factors can preoperatively predict the PNI status of RC noninvasively,which facilitates individualized treatment of RC patients.

Predicting potential invasion risks of Leucaena leucocephala(Lam.)de Wit in the arid area of Saudi Arabia

The presence of invasive plant species poses a substantial ecological impact,thus comprehensive evaluation of their potential range and risk under the influence of climate change is necessary.This study uses maximum entropy(MaxEnt)modeling to forecast the likelihood of Leucaena leucocephala(Lam.)de Wit invasion in Saudi Arabia under present and future climate change scenarios.Utilizing the MaxEnt modeling,we integrated climatic and soil data to predict habitat suitability for the invasive species.We conducted a detailed analysis of the distribution patterns of the species,using climate variables and ecological factors.We focused on the important influence of temperature seasonality,temperature annual range,and precipitation seasonality.The distribution modeling used robust measures of area under the curve(AUC)and receiver-operator characteristic(ROC)curves,to map the invasion extent,which has a high level of accuracy in identifying appropriate habitats.The complex interaction that influenced the invasion of L.leucocephala was highlighted by the environmental parameters using Jackknife test.Presently,the actual geographic area where L.leucocephala was found in Saudi Arabia was considerably smaller than the theoretical maximum range,suggesting that it had the capacity to expand further.The MaxEnt model exhibited excellent prediction accuracy and produced reliable results based on the data from the ROC curve.Precipitation and temperature were the primary factors influencing the potential distribution of L.leucocephala.Currently,an estimated area of 216,342 km^(2)in Saudi Arabia was at a high probability of invasion by L.leucocephala.We investigated the potential for increased invasion hazards in the future due to climate change scenarios(Shared Socioeconomic Pathways(SSPs)245 and 585).The analysis of key climatic variables,including temperature seasonality and annual range,along with soil properties such as clay composition and nitrogen content,unveiled their substantial influence on the distribution dynamic of L.leucocephala.Our findings indicated a significant expansion of high risk zones.High-risk zones for L.leucocephala invasion in the current climate conditions had notable expansions projected under future climate scenarios,particularly evident in southern Makkah,Al Bahah,Madina,and Asir areas.The results,backed by thorough spatial studies,emphasize the need to reduce the possible ecological impacts of climate change on the spread of L.leucocephala.Moreover,the study provides valuable strategic insights for the management of invasion,highlighting the intricate relationship between climate change,habitat appropriateness,and the risks associated with invasive species.Proactive techniques are suggested to avoid and manage the spread of L.leucocephala,considering its high potential for future spread.This study enhances the overall comprehension of the dynamics of invasive species by combining modeling techniques with ecological knowledge.It also provides valuable information for decision-making to implement efficient conservation and management strategies in response to changing environmental conditions.

Impacts of road on plant invasions in the Middle Mountain region of central Nepal

Biological invasion is triggered by human development activities such as the construction and expansion of road networks.Road verges serve as important habitats and corridors for the distribution of invasive alien plant species(IAPS)between geographically distant habitats.However,the trajectory of plant invasion and the data regarding the impact of roads on IAPS distribution are relatively poor in Nepal.Here,we surveyed two road types(main roads and feeder road)in the Middle Mountain region of central Nepal in order to investigate how different road types are driving the dispersal of IAPS along road verges and the adjacent natural habitats.Systematic sampling was conducted at ca 2.5 km intervals along the roads.At each sampling site,paired plots(25 m×4 m)were sampled:one adjacent to and along the road,and another 20 m away and parallel to it in the interior habitat.Our results revealed that the main road verges had a higher cover(33%)and a larger number of IAPS(14 species)than the feeder road(25%;10 species).The IAPS cover and richness were significantly higher along verges than in the adjacent interior habitats for both road types,indicating that roads are contributing as corridors for the dispersal of IAPS in the Middle Mountain areas of central Nepal.Further,elevation,tree canopy,and disturbances(grazing/mowing/trampling)were found to be the key factors that determine spatial distribution of IAPS along road verges.We emphasize that regular monitoring of vegetation along the road verges can help with the early detection and control of potential IAPS in the region before they become problematic.

Solitary extraovarian primary peritoneal carcinoma with direct invasion into the liver,diaphragm and lung without peritoneal dissemination or distant metastasis

To the Editor:Extraovarian primary peritoneal carcinoma(EOPPC)is an uncommon malignancy with many similarities to epithelial ovarian carcinoma in histological,clinical,and etiological aspects[1].This phenomenon is explained by their common embryonal origin,in which both develop from the coelomic epithelium in the early embryological stage.Despite their similarities,the incidence of EOPPC is significantly lower than that of epithelial ovarian carcinoma(6.78 cases per million vs.120.5 cases per million)[1].

Retraction: Emodin Inhibits Colon Cancer Cell Invasion and Migration by Suppressing Epithelial-Mesenchymal Transition via the Wnt/β-Catenin Pathway

Following the publication,concerns have been raised about a number of figures in this article.The transwell invasion assays shown in Fig.2A were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had already been published.

Retraction:MicroRNA-107 promotes proliferation,migration,and invasion of osteosarcoma cells by targeting tropomyosin 1

Following the publication,concerns have been raised about a number of figures in this article.The western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.The authors were contacted and invited to comment on the concerns raised and to provide the original,unmodified figures,but did not respond.The Editors-in-Chief therefore no longer have confidence in the integrity of the data in this article and decided to retract this article.All authors have not responded to correspondence about this retraction.

Retraction:MicroRNA-520b suppresses proliferation,migration,and invasion of spinal osteosarcoma cells via downregulation of frizzled-8

Following the publication,concerns have been raised about a number of figures in this article.The western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.The authors were contacted and invited to comment on the concerns raised and to provide the original,unmodified figures,but did not respond.The Editors-in-Chief therefore no longer have confidence in the integrity of the data in this article and decided to retract this article.All authors have not responded to correspondence about this retraction.As a responsible publisher,we hold the reliability and integrity of our published content in high regard.We deeply regret any inconvenience caused by this situation to our readers and all concerned parties.

Non-coding RNA as future target for diagnose and treatment of perineural invasion in cancers

Perineural invasion(PNI),a particularly insidious form of tumor metastasis distinct from hematogenous or lymphatic spread,has the capacity to extend well beyond the primary tumor site,infiltrating distant regions devoid of lymphatic or vascular structures.PNI often heralds a decrease in patient survival rates and is recognized as an indicator of an unfavorable prognosis across a variety of cancers.Despite its clinical significance,the underlying molecular mechanisms of PNI remain elusive,complicating the development of specific and efficacious diagnostic and therapeutic strategies.In the realm of cancer research,non-coding RNAs(ncRNAs)have attracted considerable attention due to their multifaceted roles and cancer-specific expression profiles,positioning them as promising candidates for applications in cancer diagnostics,prognostics,and treatment.Among the various types of ncRNAs,microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs)have emerged as influential players in PNI.Their involvement is increasingly recognized as a contributing factor to tumor progression and therapeutic resistance.Our study synthesizes and explores the diverse functions and mechanisms of ncRNAs in relation to PNI in cancer.This comprehensive review aims to shed light on cutting-edge perspectives that could pave the way for innovative diagnostic and therapeutic approaches to address the challenges posed by PNI in oncology.

MAD2L2 overexpression attenuates the effects of TNF-α-induced migration and invasion capabilities in colorectal cancer cells

Background:Colorectal cancer is a major global health concern,exacerbated by tumor necrosis factor-alpha(TNF-α)and its role in inflammation,with the effects of Mitotic Arrest Deficient 2 Like 2(MAD2L2)in this context still unclear.Methods:The colorectal carcinoma cell lines HCT116 and SW620 were exposed to TNF-αfor a period of 24 h to instigate an inflammatory response.Subsequent assessments were conducted to measure the expression of inflammatory cytokines,the activity within the p38 mitogen-activated protein kinase(p38 MAPK)and Phosphoinositide 3-Kinase/AKT Serine/Threonine Kinase pathway(PI3K/AKT)signaling cascades.Transcriptome sequencing and subsequent integrative analysis with the Cancer Genome Atlas(TCGA)program database revealed a significant downregulation of the key factor MAD2L2.Enhancement of MAD2L2 expression was facilitated via lentiviral vector-mediated transfection.The influence of this overexpression on TNF-α-prompted inflammation,intracellular signaling pathways,and the migratory and invasive behaviors of the colorectal cancer cells was then scrutinized.Results:TNF-αtreatment significantly increased the expression of Interleukin-1 beta(IL-1β)and Interleukin-6(IL-6),activated the MAPK p38 and PI3K/AKT signaling pathways,and enhanced cell migration and invasion.A decrease in MAD2L2 expression was observed following TNF-αtreatment.However,overexpression of MAD2L2 reversed the effects of TNF-α,reducing IL-1βand IL-6 levels,attenuating PI3K/AKT pathway activation,and inhibiting cell migration and invasion.Conclusions:Overexpression of MAD2L2 attenuates the pro-inflammatory effects of TNF-α,suggesting that MAD2L2 plays a protective role against TNF-α-induced migration and invasion of colorectal carcinoma cells.Therefore,MAD2L2 holds potential as a therapeutic target in the treatment of colorectal cancer.

Herbivore and native plant diversity synergistically resist alien plant invasion regardless of nutrient conditions

Alien plant invasion success can be inhibited by two key biotic factors:native herbivores and plant diversity.However,few studies have experimentally tested whether these factors interact to synergistically resist invasion success,especially factoring in changing global environments(e.g.nutrient enrichment).Here we tested how the synergy between native herbivores and plant diversity affects alien plant invasion success in various nutrient conditions.For this purpose,we exposed alien plant species in potmesocosms to different levels of native plant diversity(4 vs.8 species),native generalist herbivores,and high and low soil nutrient levels.We found that generalist herbivores preferred alien plants to native plants,inhibiting invasion success in a native community.This inhibition was amplified by highly diverse native communities.Further,the amplified effect between herbivory and native plant diversity was independent of nutrient conditions.Our results suggest that a higher diversity of native communities can strengthen the resistance of native generalist herbivores to alien plant invasions by enhancing herbivory tolerance.The synergistic effect remains in force in nutrient-enriched habitats that are always invaded by alien plant species.Our results shed light on the effective control of plant invasions using multi-trophic means,even in the face of future global changes.

Evaluating microvascular invasion in hepatitis B virus-related hepatocellular carcinoma based on contrast-enhanced computed tomography radiomics and clinicoradiological factors

BACKGROUND Microvascular invasion(MVI)is a significant indicator of the aggressive behavior of hepatocellular carcinoma(HCC).Expanding the surgical resection margin and performing anatomical liver resection may improve outcomes in patients with MVI.However,no reliable preoperative method currently exists to predict MVI status or to identify patients at high-risk group(M2).AIM To develop and validate models based on contrast-enhanced computed tomo-graphy(CECT)radiomics and clinicoradiological factors to predict MVI and identify M2 among patients with hepatitis B virus-related HCC(HBV-HCC).The ultimate goal of the study was to guide surgical decision-making.METHODS A total of 270 patients who underwent surgical resection were retrospectively analyzed.The cohort was divided into a training dataset(189 patients)and a validation dataset(81)with a 7:3 ratio.Radiomics features were selected using intra-class correlation coefficient analysis,Pearson or Spearman’s correlation analysis,and the least absolute shrinkage and selection operator algorithm,leading to the construction of radscores from CECT images.Univariate and multivariate analyses identified significant clinicoradiological factors and radscores associated with MVI and M2,which were subsequently incorporated into predictive models.The models’performance was evaluated using calibration,discrimination,and clinical utility analysis.RESULTS Independent risk factors for MVI included non-smooth tumor margins,absence of a peritumoral hypointensity ring,and a high radscore based on delayed-phase CECT images.The MVI prediction model incorporating these factors achieved an area under the curve(AUC)of 0.841 in the training dataset and 0.768 in the validation dataset.The M2 prediction model,which integrated the radscore from the 5 mm peritumoral area in the CECT arterial phase,α-fetoprotein level,enhancing capsule,and aspartate aminotransferase level achieved an AUC of 0.865 in the training dataset and 0.798 in the validation dataset.Calibration and decision curve analyses confirmed the models’good fit and clinical utility.CONCLUSION Multivariable models were constructed by combining clinicoradiological risk factors and radscores to preoper-atively predict MVI and identify M2 among patients with HBV-HCC.Further studies are needed to evaluate the practical application of these models in clinical settings.

Application of texture signatures based on multiparameter-magnetic resonance imaging for predicting microvascular invasion in hepatocellular carcinoma:Retrospective study

BACKGROUND Despite continuous changes in treatment methods,the survival rate for advanced hepatocellular carcinoma(HCC)patients remains low,highlighting the importance of diagnostic methods for HCC.AIM To explore the efficacy of texture analysis based on multi-parametric magnetic resonance(MR)imaging(MRI)in predicting microvascular invasion(MVI)in preoperative HCC.METHODS This study included 105 patients with pathologically confirmed HCC,categorized into MVI-positive and MVI-negative groups.We employed Original Data Analysis,Principal Component Analysis,Linear Discriminant Analysis(LDA),and Non-LDA(NDA)for texture analysis using multi-parametric MR images to predict preoperative MVI.The effectiveness of texture analysis was determined using the B11 program of the MaZda4.6 software,with results expressed as the misjudgment rate(MCR).RESULTS Texture analysis using multi-parametric MRI,particularly the MI+PA+F dimensionality reduction method combined with NDA discrimination,demonstrated the most effective prediction of MVI in HCC.Prediction accuracy in the pulse and equilibrium phases was 83.81%.MCRs for the combination of T2-weighted imaging(T2WI),arterial phase,portal venous phase,and equilibrium phase were 22.86%,16.19%,20.95%,and 20.95%,respectively.The area under the curve for predicting MVI positivity was 0.844,with a sensitivity of 77.19%and specificity of 91.67%.CONCLUSION Texture analysis of arterial phase images demonstrated superior predictive efficacy for MVI in HCC compared to T2WI,portal venous,and equilibrium phases.This study provides an objective,non-invasive method for preoperative prediction of MVI,offering a theoretical foundation for the selection of clinical therapy.

Sinonasal teratocarcinosarcoma involving the nasal cavity,unilateral paranasal sinuses,and intracranial invasion:A case report

BACKGROUND Sinonasal teratocarcinosarcoma(SNTCS)is a rare and highly invasive neoplasm originating from the nasal cavity and sinuses.Typically,it exhibits an invasive behavior towards adjacent structures;however,in exceptional instances,it may infiltrate the intracranial compartment.Due to the tumor's rarity and lack of distinctive features on computed tomography(CT)and magnetic resonance imaging(MRI)images,SNTCS is often misdiagnosed.CASE SUMMARY In this study,we present a case of SNTCS in a 56-year-old patient who exhibited unexplained cognitive impairment before admission.CT and MRI scans revealed the presence of a mass in the right nasal cavity,with lesions extending to the right ethmoid sinus and right frontal region.Subsequently,the patient underwent pathological examination for confirmation and received surgical intervention to excise the tumor.The future advancement in our understanding of this disease will significantly contribute to the precise diagnosis and treatment of SNTCS.CONCLUSION SNTCS is an exceptionally rare malignant tumor that originates from the nasal cavity and paranasal sinuses,presenting a diagnostic challenge due to its nonspecific imaging findings.MRI accurately delineates the location,morphological characteristics,size,internal structure,extent of surrounding involvement,and metabolic information of the lesion.These aspects play a pivotal role in the precise localization and qualitative assessment of SNTCS.Nevertheless,a definitive diagnosis still requires a pathological biopsy.

Immune-related long noncoding RNA zinc finger protein 710-AS1-201 promotes the metastasis and invasion of gastric cancer cells

BACKGROUND Gastric cancer(GC)is a prevalent malignant tumor of the gastrointestinal system.ZNF710 is a transcription factor(TF),and zinc finger protein 710(ZNF710)-AS1-201 is an immune-related long noncoding RNA(lncRNA)that is upregulated in GC cells.AIM To assess the correlation between ZNF710-AS1-201 and immune microenvir-onment features and to investigate the roles of ZNF710-AS1-201 in the invasion and metastasis processes of GC cells.METHODS We obtained data from The Cancer Genome Atlas and Wujin Hospital.We assessed cell growth,migration,invasion,and programmed cell death using cell counting kit-8,EdU,scratch,Transwell,and flow cytometry assays.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to identify the potential downstream targets of ZNF710-AS1-201.RESULTS In GC tissues with low ZNF710-AS1-201 expression,immunoassays detected significant infiltration of various antitumor immune cells,such as memory CD8 T cells and activated CD4 T cells.In the low-expression group,the half-maximal inhibitory concentrations(IC_(50)s)of 5-fluorouracil,cisplatin,gemcitabine,and trametinib were lower,whereas the IC_(50)s of dasatinib and vorinostat were higher.The malignant degree of GC was higher and the stage was later in the high-expression group.Additionally,patients with high expression of ZNF710-AS1-201 had lower overall survival and disease-free survival rates.In vitro,the overexpression of ZNF710-AS1-201 greatly enhanced growth,metastasis,and infiltration while suppressing cell death in HGC-27 cells.In contrast,the reduced expression of ZNF710-AS1-201 greatly hindered cell growth,enhanced apoptosis,and suppressed the metastasis and invasion of MKN-45 cells.The expression changes in ZNF710 were significant,but the corresponding changes in isocitrate dehydrogenase-2,Semaphorin 4B,ARHGAP10,RGMB,hsa-miR-93-5p,and ZNF710-AS1-202 were not consistent or statistically significant after overexpression or knockdown of ZNF710-AS1-201,as determined by qRT-PCR.CONCLUSION Immune-related lncRNA ZNF710-AS1-201 facilitates the metastasis and invasion of GC cells.It appears that ZNF710-AS1-201 and ZNF710 have potential as effective targets for therapeutic intervention in GC.Nevertheless,it is still necessary to determine the specific targets of the ZNF710 TF.

Correlation between TEX14 and ADAM17 expressions in colorectal cancer tissues of elderly patients and neoplasm staging,invasion,and metastasis

BACKGROUND Colorectal cancer(CRC)is one of the most frequently encountered malignant tumors in clinical settings.Proteins encoded by the testis-expressed gene 14(TEX14)are imperative for spermatogenesis,necessitating intercellular bridges between germ cells.Anomalous expression of TEX14 has also been associated with the proliferation and differentiation of certain tumor cells.Recombinant A disintegrin and metalloprotease 17(ADAM17)is known as a membrane-bound protease that regulates cellular activities and signal transduction by hydrolyzing various substrate proteins on the cell membrane.We hypothesize that TEX14 and ADAM17 may serve as potential biomarkers influencing the staging,invasion,and metastasis of CRC.AIM To probe the correlation between TEX17 and ADAM17 profiles in the CRC tissues of elderly patients and their association with CRC staging,invasion,and metastasis.METHODS We gathered data from 86 elderly patients diagnosed pathologically with CRC between April 2020 and December 2023.For each patient,one sample of cancer tissue and one sample of adjacent normal tissue were harvested.Real-time fluorescence quantitative PCR measured the mRNA profiles of TEX14 and ADAM17.Immunohistochemistry ascertained the positivity rates of TEX14 and ADAM17 expressions.Clinical pathological features of neoplasm staging,invasion,and metastasis were collected,and the association between TEX14 and ADAM17 expressions and clinical pathology was evaluated.RESULTS The mRNA and expression profiles of TEX14 and ADAM17 were significantly elevated in CRC tissues.The positivity rates of TEX14 and ADAM17 proteins in CRC tissues were 70.93%and 77.91%,respectively.There were no significant differences in age,sex,pathological type,and tumor diameter between TEX14 and ADAM17-positive and-negative patients.Patients with higher tumor differentiation degree,deeper infiltration and TNM stages ranging from III to IV exhibited higher positivity rates of TEX14 and ADAM17.Patients with lymph node metastasis and distant metastasis showed higher positivity rates of TEX14 and ADAM17 than those without.Positive expressions of TEX14 and ADAM17 were highly correlated with tumor staging,invasion,and metastasis.CONCLUSION TEX14 and ADAM17 profiles were significantly elevated in the CRC tissues of elderly patients,and their high expressions were associated with tumor staging,invasion,and metastasis.

IL-17 induces NSCLC cell migration and invasion by elevating MMP19 gene transcription and expression through the interaction of p300-dependent STAT3-K631 acetylation and its Y705-phosphorylation

The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.

Histological Risk Factors for Lymph Node Metastasis in pT1 Colorectal Cancer:Does Submucosal Invasion Depth Really Matter?

Objective After endoscopic resection of colorectal cancer with submucosal invasion(pT1 CRC),additional surgical treatment is recommended if deep submucosal invasion(DSI)is present.This study aimed to further elucidate the risk factors for lymph node metastasis(LNM)in patients with pT1 CRC,especially the effect of DSI on LNM.Methods Patients with pT1 CRC who underwent lymph node dissection were selected.The Chi-square test and multivariate logistic regression were used to analyze the relationship between clinicopathological characteristics and LNM.The submucosal invasion depth(SID)was measured via 4 methods and analyzed with 3 cut-off values.Results Twenty-eight of the 239 patients presented with LNM(11.7%),and the independent risk factors for LNM included high histological grade(P=0.003),lymphovascular invasion(LVI)(P=0.004),intermediate to high budding(Bd 2/3)(P=0.008),and cancer gland rupture(CGR)(P=0.008).Moreover,the SID,width of submucosal invasion(WSI),and area of submucosal invasion(ASI)were not significantly different.When one,two,three or more risk factors were identified,the LNM rates were 1.1%(1/95),12.5%(7/56),and 48.8%(20/41),respectively.Conclusion Indicators such as the SID,WSI,and ASI are not risk factors for LNM and are subjective in their measurement,which renders them relatively inconvenient to apply in clinical practice.In contrast,histological grade,LVI,tumor budding and CGR are relatively straightforward to identify and have been demonstrated to be statistically significant.It would be prudent to focus on these histological factors rather than subjective measurements.

Endometrial carcinoma with cervical stromal invasion:Three case reports

BACKGROUND Endometrial cancer is a kind of well-known tumors of female genitourinary system.Cervical stromal invasion is an adverse factor for poor prognosis of endometrial cancer.There is still controversy regarding the use of magnetic resonance imaging(MRI)in the diagnosis of cervical stromal invasion of endometrial cancer.The diagnosis of cervical stromal invasion varies significantly between different observers and institutions.We present a limited case series of the particular pattern of endometrial cancer,which infiltrates the cervical stroma and is often overlooked.CASE SUMMARY We present three cases of endometrial carcinoma with cervical stromal invasion with cancer-free uterine cavity.One patient,a reproductive-aged woman,exhibited irregular menstruation and was diagnosed with endometrial polyps by hysteroscopy and segmental curettage.A MRI scan revealed polypoid nodules within the internal cervical orifice.The other two cases were postmenopausal women who presented with abnormal vaginal bleeding.Hysteroscopy and segmental curettage suggested atypical hyperplasia of the endometrium.MRI scans did not detect any malignant signs in the endometrium.In one case,a nonthickened endometrium was observed,while in another,hyperplasia of the endometrium was seen.Notably,none of these patients had malignant tumors identified in the uterine cavity via MRI scans.However,postoperative pathological results following hysterectomy consistently indicated cervical stromal invasion.CONCLUSION Cervical stromal invasion is easily missed if no cancer is found in the uterine body on MRI.Immunohistochemistry of endoscopic curettage specimens should be conducted to avoid underestimation of the disease.

Regulation of TMEM100 expression by epigenetic modification,effects on proliferation and invasion of esophageal squamous carcinoma

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a prevalent malignancy with a high morbidity and mortality rate.TMEM100 has been shown to be suppressor gene in a variety of tumors,but there are no reports on the role of TMEM100 in esophageal cancer(EC).AIM To investigate epigenetic regulation of TMEM100 expression in ESCC and the effect of TMEM100 on ESCC proliferation and invasion.METHODS Firstly,we found the expression of TMEM100 in EC through The Cancer Genome Atlas database.The correlation between TMEM100 gene expression and the survival of patients with EC was further confirmed through Kaplan-Meier analysis.We then added the demethylating agent 5-AZA to ESCC cell lines to explore the regulation of TMEM100 expression by epigenetic modification.To observe the effect of TMEM100 expression on tumor proliferation and invasion by overexpressing TMEM100.Finally,we performed gene set enrichment analysis using the Kyoto Encyclopaedia of Genes and Genomes Orthology-Based Annotation System database to look for pathways that might be affected by TMEM100 and verified the effect of TMEM100 expression on the mitogen-activated protein kinases(MAPK)pathway.RESULTS In the present study,by bioinformatic analysis we found that TMEM100 was lowly expressed in EC patients compared to normal subjects.Kaplan-meier survival analysis showed that low expression of TMEM100 was associated with poor prognosis in patients with EC.Then,we found that the demethylating agent 5-AZA resulted in increased expression of TMEM100 in ESCC cells[quantitative real-time PCR(qRT-PCR)and western blotting].Subsequently,we confirmed that overexpression of TMEM100 leads to its increased expression in ESCC cells(qRT-PCR and western blotting).Overexpression of TMEM100 also inhibited proliferation,invasion and migration of ESCC cells(cell counting kit-8 and clone formation assays).Next,by enrichment analysis,we found that the gene set was significantly enriched in the MAPK signaling pathway.The involvement of TMEM100 in the regulation of MAPK signaling pathway in ESCC cell was subsequently verified by western blotting.CONCLUSION TMEM100 is a suppressor gene in ESCC,and its low expression may lead to aberrant activation of the MAPK pathway.Promoter methylation may play a key role in regulating TMEM100 expression.