Biological factors driving colorectal cancer metastasis

Approximately 20%of colorectal cancer(CRC)patients present with metastasis at diagnosis.Among Stage I-III CRC patients who undergo surgical resection,18%typically suffer from distal metastasis within the first three years following initial treatment.The median survival duration after the diagnosis of metastatic CRC(mCRC)is only 9 mo.mCRC is traditionally considered to be an advanced stage malignancy or is thought to be caused by incomplete resection of tumor tissue,allowing cancer cells to spread from primary to distant organs;however,increa-sing evidence suggests that the mCRC process can begin early in tumor development.CRC patients present with high heterogeneity and diverse cancer phenotypes that are classified on the basis of molecular and morphological alterations.Different genomic and nongenomic events can induce subclone diversity,which leads to cancer and metastasis.Throughout the course of mCRC,metastatic cascades are associated with invasive cancer cell migration through the circulatory system,extravasation,distal seeding,dormancy,and reactivation,with each step requiring specific molecular functions.However,cancer cells presenting neoantigens can be recognized and eliminated by the immune system.In this review,we explain the biological factors that drive CRC metastasis,namely,genomic instability,epigenetic instability,the metastatic cascade,the cancer-immunity cycle,and external lifestyle factors.Despite remarkable progress in CRC research,the role of molecular classification in therapeutic intervention remains unclear.This review shows the driving factors of mCRC which may help in identifying potential candidate biomarkers that can improve the diagnosis and early detection of mCRC cases.

RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

RARRES2's impact on lipid metabolism in triplenegative breast cancer:a pathway to brain metastasis

Breast cancer brain metastasis(BCBrM)is a crucial and hard area of research which guarantees an urgent need to understand the underlying molecular mechanisms.A recent study by Li et al.[1]published in Military Medical Research investigated the role of retinoic acid receptor responder 2(RARRES2)in regulating lipid metabolism in BCBrM,highlighting the clinical relevance of alterations in lipid metabolites,such as phosphatidylcholine(PC)and triacylglycerols(TAGs),by RARRES2 through the modulation of phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway.This commentary aims to elaborate on the key findings and their relevance to the field.

Gastric metastasis of small cell lung carcinoma:Three case reports and review of literature

BACKGROUND Small cell lung carcinoma(SCLC)is highly susceptible to metastasis in the early stages of the disease.However,the stomach is an uncommon site of metastasis in SCLC,and only a few cases of this type of metastasis have been reported.Therefore,SCLC gastric metastases have not been systematically characterized and are easily missed and misdiagnosed.CASE SUMMARY We report three cases of gastric metastasis from SCLC in this article.The first patient presented primarily with cough,hemoptysis,and epigastric fullness.The other two patients presented primarily with abdominal discomfort,epigastric distension,and pain.All patients underwent gastroscopy and imaging examinations.Meanwhile,the immunohistochemical results of the lesions in three patients were suggestive of small cell carcinoma.Finally,the three patients were diagnosed with gastric metastasis of SCLC through a comprehensive analysis.The three patients did not receive appropriate treatment and died within a short time.CONCLUSION Here,we focused on summarizing the characteristics of gastric metastasis of SCLC to enhance clinicians'understanding of this disease.

Impact of preoperative inflammatory and nutritional markers on the prognosis of patients with peritoneal metastasis of colorectal cancer

BACKGROUND Identifying patients with peritoneal metastasis(PMs)of colorectal cancer(CRC)who will benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is crucial before surgery.Inflammatory and nutritional indicators play essential roles in cancer development and metastasis.AIM To investigate the association of preoperative inflammatory and nutritional markers with prognosis in patients with CRC-PM.METHODS We included 133 patients diagnosed with CRC-PM between July 2012 and July 2018.Patients’demographics,overall survival(OS),and preoperative inflammatory and nutritional markers were evaluated.The Kaplan-Meier method and log-rank test were used to estimate differences.RESULTS Of the 133 patients,94(70.6%)had normal hemoglobin(Hb)and 54(40.6%)had a high neutrophil-to-lymphocyte ratio(NLR).The median OS(mOS)was significantly lower for patients with high NLR(7.9 months)than for those with low NLR(25.4 months;P=0.002).Similarly,patients with normal Hb had a longer mOS(18.5 months)than those with low Hb(6.3 months;P<0.001).Multivariate analysis identified age,carbohydrate antigen 199 levels,NLR,Hb,and peritoneal cancer index as independent predictors of OS.Based on these findings,a nomogram was constructed,which demonstrated a good capacity for prediction,with a C-index of 0.715(95%confidence interval:0.684-0.740).Furthermore,the 1-and 2-year survival calibration plots showed good agreement between predicted and actual OS rates.The areas under the curve for the 1-and 2-year survival predictions of the nomogram were 0.6238 and 0.6234,respectively.CONCLUSION High NLR and low Hb were identified as independent predictive risk factors for poor prognosis in patients with CRC-PM.The established nomogram demonstrated high accuracy in predicting OS for patients with CRC-PM,indicating its potential as a valuable prognostic tool for this patient population.

Inetetamab combined with pyrotinib and chemotherapy in the treatment of breast cancer brain metastasis: A case report

BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In this context,we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb(ine-tetamab)combined with a small molecule tyrosine kinase inhibitor(TKI).CASE SUMMARY The patient was a 58-year-old woman with a 12-year history of type 2 diabetes.She was compliant with regular insulin treatment and had good blood glucose control.The patient was diagnosed with invasive carcinoma of the right breast(T3N1M0 stage IIIa,HER2-positive type)through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019.Immunohistochemistry showed ER(-),PR(-),HER-2(3+),and Ki-67(55-60%+).Preoperative neoadjuvant chemotherapy,i.e.,the AC-TH regimen(epirubicin,cyclophosphamide,docetaxel-paclitaxel,and trastuzumab),was administered for 8 cycles.She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year.Brain metastasis was found 9 mo after surgery.She underwent brain metastasectomy in August 2020.Immunohistochemistry showed ER(-)and PR.(-),HER-2(3+),and Ki-67(10-20%+).In November 2020,the patient experienced headache symptoms.After an examination,tumor recurrence in the original surgical region of the brain was observed,and the patient was treated with inetetamab,pyrotinib,and capecitabine.Whole-brain radiotherapy was recommended.The patient and her family refused radiotherapy for personal reasons.In September 2021,a routine examination revealed that the brain tumor was considerably larger.The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases,followed by regular hospitalization and routine examinations.The patient’s condition is generally stable,and she has a relatively high quality of life.This case report demonstrates that in patients with BCBM and resistance to trastuzumab,inetetamab combined with pyrotinib and chemotherapy can prolong survival.CONCLUSION Inetetamab combined with small molecule TKI drugs,chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.

Gastric cancer liver metastasis will reduce the efficacy of immunotherapy

Immune checkpoint inhibitors augment the antitumor activity of T cells by inhibiting the negative regulatory pathway of T cells,leading to notable efficacy in patients with non-small cell lung cancer,melanoma,and other malignancies through immunotherapy utilization.However,secondary malignant liver tumors not only lower the liver's sensitivity to immunotherapy but also trigger systemic immune suppression,resulting in reduced overall effectiveness of immune therapy.Patients receiving immunotherapy for non-small cell lung cancer and melanoma experience reduced response rates,progression-free survival,and overall survival when secondary malignant tumors develop in the liver.Through Liu's retrospective analysis,valuable insights are provided for the future clinical management of these patients.Therefore,in patients with gastric cancer(GC),the occurrence of liver metastasis might be indicative of reduced efficacy of immuno-therapy.Overcoming liver immune tolerance mechanisms and their negative impacts allows for the potential benefits of immunotherapy in patients with GC and liver metastasis.INTRODUCTION Gastric cancer(GC)ranks among the prevalent malignancies affecting the digestive system globally.Based on the latest epidemiological data[1,2],it holds the fifth position for incidence and the fourth position for mortality among all malignant tumors.GC cases and fatalities in China make up roughly half of the worldwide figures.Earlier investigations[3]have demonstrated that the median overall survival(mOS)among advanced GC patients left untreated typically ranges from 3 to 4 months.Systemic chemotherapy recipients often experience a mOS of around one year,accompanied by a marked improvement in the quality of life among patients with advanced GC.The mainstay of treatment for advanced GC patients involves chemotherapeutic medications such as fluoropyrimidines,platinum compounds,and taxanes.However,their efficacy in tumor control is constrained by acquired resistance and primary resistance.The rise of personalized precision therapy has propelled immunotherapy into the spotlight as a crucial component of comprehensive treatment[4].By blocking the negative regulatory pathways of T cells,immune checkpoint inhibitors(ICIs)boost the anti-tumor effect of T cells.Immunotherapy has brought about significant therapeutic benefits for patients diagnosed with non-small cell lung cancer,melanoma,and related illnesses[5,6],instilling newfound hope in those with advanced GC[7].However,phase III clinical trial data[8-12]reveals that the incorporation of immunotherapy into chemotherapy regimens improves overall survival(OS)outcomes for patients with advanced GC.The liver's immune-exempt nature renders it less responsive to immunotherapy when secondary malignant tumors are present,fostering systemic immune suppression and yielding unfavorable outcomes in immune therapy[13-15].In retrospective research[16-20]pertaining to non-small cell lung cancer and melanoma,it has been observed that the presence of secondary liver malignancies may lower the response rate,progression-free survival(PFS),and OS rates in patients treated with immunotherapy,independent of factors such as tumor mutation burden and PD-L1 expression.Despite this,there is a paucity of studies examining whether the existence of secondary malignant liver tumors affects the effectiveness of immunotherapy in patients diagnosed with advanced HER-2 negative GC.

Radiotherapy for hyoid bone metastasis from lung adenocarcinoma:A case report

BACKGROUND Metastasis to the hyoid bone is an exceptionally rare occurrence,with documented cases limited to breast,liver,colon,skin,lung,and prostate cancers.This report highlights an unusual case involving the metastasis of lung adenocarcinoma to the hyoid bone,accompanied by a distinctive headache.Previous documentation involved surgical resection of the hyoid mass.We present a case displaying the benefits of palliative radiotherapy.CASE SUMMARY A 72-year-old non-smoking,non-alcoholic woman,initially under investigation for a year-long elevation in absolute lymphocyte count,presented with a monthlong history of intermittent throat pain.Despite negative findings in gastroenterological and otolaryngologic examinations,a contrast-enhanced chest computed tomography scan revealed a mediastinal mass and questionable soft tissue thickening in her left anterolateral neck.Subsequent imaging and biopsies confirmed the presence of lung adenocarcinoma metastasis to the hyoid bone.The patient was treated with platinum-based chemo-immunotherapy along with pembrolizumab.Ultimately,the lung cancer was unresponsive.Our patient opted for palliative radiation therapy instead of surgical resection to address her throat pain.As a result,her throat pain was alleviated,and it also incidentally resolved her chronic headaches.This is the second documented case of lung adenocarcinoma metastasizing to the hyoid bone.CONCLUSION Palliative radiotherapy may add to the quality of life in symptomatic patients with cancer metastatic to the hyoid bone.

Prognostic factors of breast cancer brain metastasis

In this editorial we comment on the article by Chen et al published in the recent issue of the World Journal of Clinical Oncology.Brain metastasis is one of the most serious complications of breast cancer and causes high morbidity and mortality.Brain metastases may involve the brain parenchyma and/or leptomeninges.Symptomatic brain metastases develop in 10%-16%of newly recognized cases each year,and this rate increases to 30%in autopsy series.Depending on the size of the metastatic foci,it may be accompanied by extensive vasogenic edema or may occur as small tumor foci.Since brain metastases are a significant cause of morbidity and mortality,early diagnosis can have significant effects on survival and quality of life.The risk of developing brain metastases emerges progressively due to various patient and tumor characteristics.Patient variability may be particularly important in the susceptibility and distribution of brain metastases because malignant blood must cross the brain barrier and move within the brain parenchyma.Some characteristics of the tumor,such as gene expression,may increase the risk of brain metastasis.Clinical growth,tumor stage,tumor grade,growth receptor positivity,HER2 positivity,molecular subtype(such as triple negative status,luminal/nonluminal feature)increase the risk of developing breast cancer metastasis.Factors related to survival due to breast cancer brain metastasis include both tumor/patient characteristics and treatment characteristics,such as patient age,lung metastasis,surgery for brain metastasis,and HER2 positivity.If cases with a high risk of developing brain metastasis can be identified with the help of clinical procedures and artificial intelligence,survival and quality of life can be increased with early diagnosis and treatment.At the same time,it is important to predict the formation of this group in order to develop new treatment methods in cases with low survival expectancy with brain metastases.

Injectable Nanorobot-Hydrogel Superstructure for Hemostasis and Anticancer Therapy of Spinal Metastasis

Surgery remains the standard treatment for spinal metastasis.However,uncontrolled intraoperative bleeding poses a significant challenge for adequate surgical resection and compromises surgical outcomes.In this study,we develop a thrombin(Thr)-loaded nanorobothydrogel hybrid superstructure by incorporating nanorobots into regenerated silk fibroin nanofibril hydrogels.This superstructure with superior thixotropic properties is injected percutaneously and dispersed into the spinal metastasis of hepatocellular carcinoma(HCC)with easy bleeding characteristics,before spinal surgery in a mouse model.Under near-infrared irradiation,the self-motile nanorobots penetrate into the deep spinal tumor,releasing Thr in a controlled manner.Thr-induced thrombosis effectively blocks the tumor vasculature and reduces bleeding,inhibiting tumor growth and postoperative recurrence with Au nanorod-mediated photothermal therapy.Our minimally invasive treatment platform provides a novel preoperative therapeutic strategy for HCC spinal metastasis effectively controlling intraoperative bleeding and tumor growth,with potentially reduced surgical complications and enhanced operative outcomes.

Game-changing insights on vertebral skeletal stem cells in bone metastasis and therapeutic horizons

Greenblatt and his team have unveiled vertebral skeletal stem cells(vSSCs)as a critical player in the landscape of bone metastasis.This commentary delves into the transformative discoveries surrounding vSSCs,emphasizing their distinct role in bone metastasis compared to other stem cell lineages.We illuminate the unique properties and functions of vSSCs,which may account for the elevated susceptibility of vertebral bones to metastatic invasion.Furthermore,we explore the exciting therapeutic horizons opened by this newfound understanding.These include potential interventions targeting vSSCs,modulation of associated signaling pathways,and broader implications for the treatment and management of bone metastasis.By shedding light on these game-changing insights,we hope to pave the way for novel strategies that could revolutionize the prognosis and treatment landscape for cancer patients with metastatic bone disease.

Role of cancer stem cell ecosystem on breast cancer metastasis and related mouse models

Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and microenvironment.Breast cancer stem cells(BCSCs)constitute a small population of cancer cells with unique characteristics,including their capacity for self-renewal and differentiation.Studies have shown that BCSCs not only drive tumorigenesis but also play a crucial role in promoting metastasis in breast cancer.The tumor microenvironment(TME),composed of stromal cells,immune cells,blood vessel cells,fibroblasts,and microbes in proximity to cancer cells,is increasingly recognized for its crosstalk with BCSCs and role in BCSC survival,growth,and dissemination,thereby influencing metastatic ability.Hence,a thorough understanding of BCSCs and the TME is critical for unraveling the mechanisms underlying breast cancer metastasis.In this review,we summarize current knowledge on the roles of BCSCs and the TME in breast cancer metastasis,as well as the underlying regulatory mechanisms.Furthermore,we provide an overview of relevant mouse models used to study breast cancer metastasis,as well as treatment strategies and clinical trials addressing BCSC-TME interactions during metastasis.Overall,this study provides valuable insights for the development of effective therapeutic strategies to reduce breast cancer metastasis.

NUDT5 promotes the growth,metastasis,and Warburg effect of IDH wild-type glioblastoma multiforme cells by upregulating TRIM47

Objective:To explore the regulatory mechanism of NUDT5 in glioblastoma multiforme(GBM).Methods:GEPIA database was used to predict the expressions of NUDT5 and tripartite motif family proteins 47(TRIM47)in GBM patients.RT-qPCR and Western blot analyses were performed to examine NUDT5 expression in GBM cells.LN-229 cell proliferation,migration as well as invasion were estimated by CCK-8,colony formation,wound healing,and Transwell assays following interference with NUDT5.ECAR assay,L-lactic acid kit,glucose detection kit,and ATP detection kit were applied for the detection of glycolysis-related indexes.Co-immunoprecipitation experiment was carried out to verify the relationship between NUDT5 and TRIM47.Results:GEPIA database showed that NUDT5 expression was significantly increased in GBM patients.Inhibiting the expression of NUDT5 in GBM cells significantly suppressed the viability,proliferation,invasion,migration,and glycolysis of GBM cells.Moreover,TRIM47 was highly expressed in GBM cells and interacted with NUDT5.Overexpression of TRIM47 partially reversed the inhibitory effect of NUDT5 downregulation on the proliferation,metastasis,and glycolysis of GBM cells.Conclusions:NUDT5 promotes the growth,metastasis,and Warburg effect of GBM cells by upregulating TRIM47.Both NUDT5 and TRIM47 can be used as targets for GMB treatment.

Highβ-sitosterol-D-glucoside content in sweet potato varieties and its anti-breast cancer potential through multiple metastasis-associated signals

β-Sitosterol-D-glucoside(β-SDG)is a phytosterol compound whose antitumor activity has been confirmed by previous studies.However,its suppression on breast cancer remains unclear.To that purpose,we isolatedβ-SDG from sweet potato and investigated the breast-cancer-inhibiting mechanism using proteomic analysis.The sweet potato species S6 with highβ-SDG content were chosen form 36 species andβ-SDG was isolated by HPLC.Afterwards,an in situ animal model of breast cancer was established,andβ-SDG significantly reduced the tumor volume of MCF-7 xenograft mice.Proteomic analysis of tumor tissues revealed that 127 of these proteins were upregulated and 80 were downregulated.Gene ontology and network analysis showed that regulatory proteins were mainly associated with epithelial-mesenchymal transition(EMT),myogenesis,cholesterol homeostasis,oxidative phosphorylation and reactive oxygen pathways,while Vimentin,NDUF,VDAC1,PPP2CA and SNx9 were the most significant 5 node degree genes.Meanwhile,in vitro and in vivo results showed that the protein expression of PPP2CA and Vimentin,which are markers of EMT,were involved in breast cancer cell metastasis and could be reversed byβ-SDG.This work highlightsβ-SDG as a bioactive compound in sweet potato and the potential therapeutic effect ofβ-SDG for the treatment of breast cancer by inhibiting metastasis.

Fifty-five cases of hepatic alveolar echinococcosis combined with lymph node metastasis:A retrospective study

BACKGROUND Lymph node metastasis is a specific type of metastasis in hepatic alveolar echinococcosis(AE).Currently,there is a scarcity of describing the clinical characteristics and lymph node metastasis rules of patients with hepatic AE combined with lymph node metastasis and its mechanism and management are still controversial.Radical hepatectomy combined with regional lymph node dissection is a better treatment.AIM To analyse the clinical features of hepatic AE combined with lymph node metastasis to explore its treatment and efficacy.METHODS A total of 623 patients with hepatic AE admitted to the First Affiliated Hospital of Xinjiang Medical University from 1 January 2012 to 1 January 2022 were retrospectively analysed.Fifty-five patients with combined lymph node metastasis were analysed for their clinical data,diagnosis and treatment methods,follow-up efficacy,and characteristics of lymph node metastasis.Finally,we comparatively analysed the lymph node metastasis rates at different sites.Categorical variables are expressed as frequencies and percentages,and the analysis of difference was performed using theχ2 test.The Bonferroni method was used for pairwise comparisons when statistical differences existed between multiple categorical variables.RESULTS A lymph node metastasis rate of 8.8%(55/623)was reported in patients with hepatic AE,with a female predilection(69.1%)and a statistically significant sex difference(χ2=8.018,P=0.005).Of the 55 patients with lymph node metastasis,72.7%had a parasite lesion,neighbouring organ invasion,and metastasis stage of P3N1M0 and above,of which 67.3%,78.2%,and 34.5%of hepatic AE lesions invaded the bile ducts,blood vessels,and distant metastases,respectively.Detection rates of lymph node metastasis of 16.4%,21.7%,and 34.2%were reported for a preoperative abdominal ultrasound,magnetic resonance imaging,and computed tomography examinations.All patients were intraoperatively suspected with enlarged lymph nodes and underwent radical hepatectomy combined with regional lymph node dissection.After surgery,a routine pathological examination was conducted on the resected lymph nodes.A total of 106 positive lymph nodes were detected in six groups at various sites,including 51 single-group metastasis cases and four multi-group metastasis cases.When the metastasis rates at different sites were statistically analysed,we observed that the metastasis rate in the para-hepatoduodenal ligament lymph nodes was significantly higher than that of the other sites(χ^(2)=128.089,P=0.000<0.05).No statistical difference was observed in the metastasis rate between the five other groups.Clavien-Dindo grade IIIa complication occurred in 14 cases,which improved after administering symptomatic treatment.Additionally,lymph node dissection-related complications were not observed.Recurrence after 2 years was observed in one patient.CONCLUSION Lymph node metastasis is a rare form of metastasis in hepatic AE,which is more frequent in women.Parahepatoduodenal ligament lymph nodes are commonly observed.Radical hepatectomy combined with regional lymph node dissection is a safe,effective,and feasible treatment for liver AE combined with lymph node metastasis.

MicroRNAs:A novel signature in the metastasis of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma(ESCC)is a malignant epithelial tumor,characterized by squamous cell differentiation,it is the sixth leading cause of cancer-related deaths globally.The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered,coupled with higher risk of metastasis,which is an exceedingly malignant charac-teristic of cancer,frequently leading to a high mortality rate.Unfortunately,there is currently no specific and effective marker to predict and treat metastasis in ESCC.MicroRNAs(miRNAs)are a class of small non-coding RNA molecules,approximately 22 nucleotides in length.miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence,progression,and prognosis of cancer.Here,we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis,and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors.This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis,with the ultimate aim of reducing the mortality rate among patients with ESCC.

Predictive value of CA-153,CA-125 and Apo A for ocular metastasis in menopausal female patients with breast cancer

AIM:To establish a meaningful standard for diagnosing ocular metastasis(OM)in menopausal breast cancer(BC)women,and explore the relationship between CA-153,CA-125,apolipoprotein A,and OM.METHODS:A total of 1362 menopausal female BC patients with OM volunteered to take part in this study between July 2012 and July 2022.Women with BC who are menopausal were found to have an OM incidence of 1.6%.Furthermore,CA-153,CA-125,and apolipoprotein A(Apo A)all contributed to OM in women with BC who are postmenopausal according to binary logistic regression.Receiver operating curve(ROC)analysis was used to assess the diagnostic value of OM in patients with BC.RESULTS:Both CA-153 and CA-153+CA-125 showed a higher sensitivity of 95.45%,whereas CA-153+Apo A illustrated the highest specificity of 99.02%.Moreover,CA-153 and CA-153+CA-125 had higher areas under the curve(AUC)of 0.973.CONCLUSION:The data indicate that the serum concentrations of CA-153 exhibited the most significant predictors of the diagnosis of OM in menopausal women with BC.The current study researches the utility of risk factors in predicting of OM in menopausal BC women and put forward the latest suggestions on their clinical application.

Myocardial metastasis from ZEB1-and TWIST-positive spindle cell carcinoma of the esophagus:A case report

BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on autopsy.Malignant tumors with a relatively high frequency of cardiac metastasis include mesothelioma,melanoma,lung cancer,and breast cancer,whereas reports of esophageal cancer with cardiac metastasis are rare.CASE SUMMARY The case of a 60-year-old man who complained of dysphagia is presented.Upper gastrointestinal endoscopy showed a submucosal tumor-like elevated lesion in the esophagus causing stenosis.Contrast-enhanced computed tomography showed left atrial compression due to the esophageal tumor,multiple liver and lung metastases,and a left pleural effusion.Pathological examination of a biopsy speci-men from the esophageal tumor showed spindle-shaped cells,raising suspicion of esophageal sarcoma.The disease progressed rapidly,and systemic chemotherapy was deemed necessary,however,due to his poor general condition,adminis-tration of cytotoxic agents was considered difficult.Given his high Combined Positive Score,nivolumab was administered,however,the patient soon died from the disease.The autopsy confirmed spindle cell carcinoma(SCC)of the esophagus and cardiac metastasis with similar histological features.Cancer stem cell markers,ZEB1 and TWIST,were positive in both the primary tumor and the cardiac metastasis.CONCLUSION To the best of our knowledge,there have been no prior reports of cardiac metastasis of esophageal SCC.This case highlights our experience with a patient with esophageal SCC who progressed rapidly and died from the disease,with the autopsy examination showing cardiac metastasis.

Deep learning-based automatic pipeline system for predicting lateral cervical lymph node metastasis in patients with papillary thyroid carcinoma using computed tomography:A multi-center study

Objective:The assessment of lateral lymph node metastasis(LLNM)in patients with papillary thyroid carcinoma(PTC)holds great significance.This study aims to develop and evaluate a deep learning-based automatic pipeline system(DLAPS)for diagnosing LLNM in PTC using computed tomography(CT).Methods:A total of 1,266 lateral lymph nodes(LLNs)from 519 PTC patients who underwent CT examinations from January 2019 to November 2022 were included and divided into training and validation set,internal test set,pooled external test set,and prospective test set.The DLAPS consists of an auto-segmentation network based on RefineNet model and a classification network based on ensemble model(ResNet,Xception,and DenseNet).The performance of the DLAPS was compared with that of manually segmented DL models,the clinical model,and Node Reporting and Data System(Node-RADS).The improvement of radiologists’diagnostic performance under the DLAPS-assisted strategy was explored.In addition,bulk RNA-sequencing was conducted based on 12 LLNs to reveal the underlying biological basis of the DLAPS.Results:The DLAPS yielded good performance with area under the receiver operating characteristic curve(AUC)of 0.872,0.910,and 0.822 in the internal,pooled external,and prospective test sets,respectively.The DLAPS significantly outperformed clinical models(AUC 0.731,P<0.001)and Node-RADS(AUC 0.602,P<0.001)in the internal test set.Moreover,the performance of the DLAPS was comparable to that of the manually segmented deep learning(DL)model with AUCs ranging 0.814−0.901 in three test sets.Furthermore,the DLAPSassisted strategy improved the performance of radiologists and enhanced inter-observer consistency.In clinical situations,the rate of unnecessary LLN dissection decreased from 33.33%to 7.32%.Furthermore,the DLAPS was associated with the cell-cell conjunction in the microenvironment.Conclusions:Using CT images from PTC patients,the DLAPS could effectively segment and classify LLNs non-invasively,and this system had a good generalization ability and clinical applicability.

The HOXC10/NOD1/ERK axis drives osteolytic bone metastasis of pan-KRAS-mutant lung cancer

While KRAS mutation is the leading cause of low survival rates in lung cancer bone metastasis patients,effective treatments are still lacking.Here,we identified homeobox C10(HOXC10)as a lynchpin in pan-KRAS-mutant lung cancer bone metastasis.