Irreversible electroporation for metastatic pancreatic carcinoma with liver metastasis:What does the evidence say

Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies.However,higher quality studies with proper controls and randomization are required to establish its superiority when added with neoadjuvant chemotherapy over the current management of choice,which is chemotherapy alone.Further studies are required before establishment of any survival benefit in metastatic pancreatic carcinoma,and such evidence is lacking at present.

Harnessing the prognostic power of preoperative systemic immuneinflammation index/albumin ratio in hepatocellular carcinoma resection

The recent study by Chen et al,published in the World Journal of Gastroenterology,introduces a groundbreaking assessment tool-the preoperative systemic immuneinflammation index/albumin(SII/ALB)ratio-for patients with hepatocellular carcinoma(HCC)undergoing curative resection.This study not only establishes the independent prognostic significance of the SII/ALB ratio but also incorporates it into a predictive nomogram,enhancing its utility for clinical decision-making.The SII/ALB ratio,by integrating inflammatory and nutritional biomarkers,offers a novel lens through which the prognosis of HCC patients can be viewed,suggesting a more tailored approach to patient management.The development of the nomogram,validated for its accuracy in predicting patient outcomes,marks a pivotal advance,potentially guiding surgical decisions and postoperative care.However,the study's focus on a single-center cohort prompts the need for validation in a broader,more diverse patient population to ensure its applicability across various clinical settings.Moreover,longitudinal studies could elucidate the dynamic changes in SII/ALB post-surgery,offering insights into its potential as a continuous monitor for recurrence and long-term survival.This abstract aim to underscore the critical findings of Chen et al's study while calling for further research to explore the full potential of the SII/ALB ratio in the global management of hepatocellular carcinoma.

Residual gastric cancer with a mixed small cell neuroendocrine and keratinizing squamous cell carcinoma:A case report

BACKGROUND Despite advancements in early detection and treatment,the prognosis and his-tological types for residual gastric cancer(GC)remains poor.CASE SUMMARY This case report presents a rare occurrence of residual GC featuring a combination of small cell neuroendocrine carcinoma(SCNEC)and squamous cell carcinoma(SCC)in a 60-year-old male patient.The patient,with a history of Billroth II gas-trectomy for duodenal ulcer bleeding,presented with gastrointestinal bleeding.Preoperative computed tomography and positron emission tomography-compu-ted tomography indicated adenocarcinoma with tumor and abdominal lymph node metastasis.The patient underwent laparoscopic total gastrectomy and ly-mph node dissection for residual GC.Histological examination of the resected tumor confirmed the presence of both SCNEC and SCC.Postoperatively,the patient underwent adjuvant chemotherapy four times.Two years later,the patient was found to occur esophageal cancer and was performed a small bowel stoma and radical esophagectomy.CONCLUSION In this case report,we detail a rare instance of residual GC with mixed SCNEC and SCC,emphasizing the complexity of diagnosis and treatment,and the need for ongoing research.

Concurrent occurrence of adenocarcinoma and urothelial carcinoma of the prostate:Coexistence mechanisms from multiple perspectives

This article discusses the coexistence of prostate adenocarcinoma and prostate urothelial carcinoma.Combining existing literature and research results,the potential mechanisms of the co-occurrence of these two cancers are explored,including the role of androgen receptor,gene mutations,and their complex interactions in cell signaling pathways,etc.Also,the hypothesis of prostate cancer transformation into urothelial carcinoma is explained from some perspectives,including tumor multipotent stem cell differentiation,epithelial-mesenchymal transition,mesenchymal-epithelial transition,and other mechanisms.Ultimately,the goal is to provide more accurate diagnoses and more personalized treatments in clinical practice,as well as to lay the foundation for improving patient prognoses in the future.

Primary parenchymal squamous cell carcinoma of the kidney:A case report

BACKGROUND Primary squamous cell carcinoma(SCC)of the renal parenchyma is extremely rare,with only nine cases reported.CASE SUMMARY This study reports a 51-year-old man with primary SCC of the renal parenchyma.The patient was admitted with recurrent dull pain and discomfort in the right lumbar region,which had worsened over 2 weeks,accompanied by painful gross hematuria.SCC antigen(SCCA)levels were elevated,and imaging revealed a renal mass with associated calculi.The patient underwent laparoscopic unilateral nephrectomy and lymph node dissection.Postoperative pathology confirmed highly differentiated SCC with necrosis in the right renal parenchyma,with negative renal pelvis and ureter.The pathological stage was Pt3aN1M0.Four months after surgery,the tumor recurred with involvement of the liver,right psoas major muscle,and inferior vena cava.The patient refused chemotherapy and succumbed to the disease 6 months postoperatively due to disease progression.CONCLUSION We report a case of primary SCC of the renal parenchyma,a rare renal malignancy.The clinical symptoms,laboratory tests,and imaging findings are nonspecific,making accurate and timely diagnosis challenging.According to the literature,for patients with renal calculi accompanied by a renal mass,elevated serum SCCA levels,and magnetic resonance imaging showing cystic or cystic-solid masses within the kidney with pseudocapsules and heterogeneous mild enhancement,the possibility of this disease should be considered.

Radiomics and molecular analysis:Bridging the gap for predicting hepatocellular carcinoma prognosis

This editorial examines a recent study that used radiomics based on computed tomography(CT)to predict the expression of the fibroblast-related gene enhancer of zeste homolog 2(EZH2)and its correlation with the survival of patients with hepatocellular carcinoma(HCC).By integrating radiomics with molecular analysis,the study presented a strategy for accurately predicting the expression of EZH2 from CT scans.The findings demonstrated a strong link between the radiomics model,EZH2 expression,and patient prognosis.This noninvasive approach provides valuable insights into the therapeutic management of HCC.

Activin A receptor type 1C single nucleotide polymorphisms associated with esophageal squamous cell carcinoma risk in Chinese population

BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.

Therapeutic potential of kakkatin derivatives against hepatocellular carcinoma

In this article,we commented on the work done by Jiang et al,where they syn-thesized a kakkatin derivative,6-(hept-6-yn-1-yloxy)-3-(4-hydroxyphenyl)-7-me-thoxy-4H-chromen-4-one(HK),and investigated its antitumor activities and me-chanism in gastric cancer MGC803 and hepatocellular carcinoma(HCC)SMMC-7721 cells.HK was evaluated for its antitumor activity as compared to kakkatin and cisplatin.This article focused on various risk factors of HCC,the mechanism of HCC progression and molecular targets of the kakkatin derivative,and limi-tations of available treatment options.HCC is a predominant form of primary liver cancer characterized by the accumulation of multiple gene modifications,overexpression of protooncogenes,altered immune microenvironment,and infilt-ration by immune cells.Puerariae flos(PF)has been used in traditional medicine in China,Korea,and Japan for lung clearing,spleen awakening,and relieving alcohol hangovers.PF exerts antitumor activity by inhibiting cancer cell prolif-eration,invasion,and migration.PF induces apoptosis in alcoholic HCC via the estrogen-receptor 1-extracellular signal-regulated kinases 1/2 signaling pathway.Kakkatin isolated from PF is known as a hepatoprotective bioflavonoid.The ka-kkatin derivative,HK,exhibited anticancer activity against HCC cell lines by in-hibiting cell proliferation and upregulating nuclear factor kappa B subunit 1 and phosphodiesterase 3B.However,further preclinical and clinical studies are required to establish its therapeutic potential against HCC.

Gamma-glutamyl transferase-to-lymphocyte ratio as a prognostic marker in patients with hepatocellular carcinoma undergoing hepatectomy

BACKGROUND We investigated the utility of gamma-glutamyl transferase-to-lymphocyte ratio(GLR)as a predictive indicator for postoperative survival in patients with hepatocellular carcinoma(HCC)across different time periods and developed a predictive model based on this.AIM To evaluate the prognostic accuracy of GLR for overall survival(OS)in patients with HCC and its impact over time.METHODS This study enrolled 301 patients with HCC treated with curative hepatectomy.Exclusion criteria included non-HCC hepatic malignancies,inadequate records,and prior cancer treatments.Baseline demographics,clinical features,and hematological parameters were recorded.Time-dependent receiver operating characteristic curve analysis was used to determine the optimal GLR threshold for survival prediction at 13 months.Statistical analyses included the Kaplan-Meier method,multivariate Cox regression,and the creation of a prognostic nomogram.RESULTS Out of 301 patients,293 were eligible for analysis,with a male predominance(84.6%).High preoperative GLR correlated with several adverse clinical features.Optimal cutoff values for GLR were significantly associated with stratification of 13-month OS.Multivariate analysis identified age,liver enzymes,postoperative transarterial chemoembolization,Child-Pugh grade,and inflammatory markers as independent predictors of OS.Notably,GLR had a significant impact on long-term postoperative OS,with its influence becoming more pronounced over time.CONCLUSION GLR can serve as a potent prognostic tool for postoperative HCC management,particularly in predicting long-term outcomes.

Development and validation of a nomogram model for predicting overall survival in patients with gastric carcinoma

BACKGROUND The prevalence and mortality rates of gastric carcinoma are disproportionately elevated in China,with the disease's intricate and varied characteristics further amplifying its health impact.Precise forecasting of overall survival(OS)is of paramount importance for the clinical management of individuals afflicted with this malignancy.AIM To develop and validate a nomogram model that provides precise gastric cancer prevention and treatment guidance and more accurate survival outcome prediction for patients with gastric carcinoma.METHODS Data analysis was conducted on samples collected from hospitalized gastric cancer patients between 2018 and 2020.Least absolute shrinkage and selection operator,univariate,and multivariate Cox regression analyses were employed to identify independent prognostic factors.A nomogram model was developed to predict gastric cancer patient outcomes.The model's predictability and discriminative ability were evaluated via receiver operating characteristic curves.To evaluate the clinical utility of the model,Kaplan-Meier and decision curve analyses were performed.RESULTS A total of ten independent prognostic factors were identified,including body mass index,tumor-node-metastasis(TNM)stage,radiation,chemotherapy,surgery,albumin,globulin,neutrophil count,lactate dehydrogenase,and platelet-to-lymphocyte ratio.The area under the curve(AUC)values for the 1-,3-,and 5-year survival prediction in the training set were 0.843,0.850,and 0.821,respectively.The AUC values were 0.864,0.820,and 0.786 for the 1-,3-,and 5-year survival prediction in the validation set,respectively.The model exhibited strong discriminative ability,with both the time AUC and time C-index exceeding 0.75.Compared with TNM staging,the model demonstrated superior clinical utility.Ultimately,a nomogram was developed via a web-based interface.CONCLUSION This study established and validated a novel nomogram model for predicting the OS of gastric cancer patients,which demonstrated strong predictive ability.Based on these findings,this model can aid clinicians in implementing personalized interventions for patients with gastric cancer.

Identifying adipocyte-derived exosomal miRNAs as potential novel prognostic markers for radiotherapy of esophageal squamous cell carcinoma

BACKGROUND Radiation resistance limits radiotherapy efficacy in esophageal squamous cell carcinoma(ESCC).The tumor microenvironment,particularly adipocytes,plays a role in promoting cancer progression.Extracellular vesicles and microRNAs(miRNAs)regulate gene expression and hold prognostic potential for esophageal carcinoma.Elucidating radioresistance mechanisms and identifying radiosensitization targets can help enhance radiotherapy efficacy for esophageal cancer.AIM To investigate the potential role of miRNAs derived from adipocyte exosomes as prognostic markers for radiotherapy efficacy in ESCC.METHODS Free adipocytes were isolated from human thoracic adipose tissue.A co-culture model of adipocytes and ESCC cells was established to observe colony formation and cell survival post-irradiation.ESCC cell apoptosis was assessed by flow cytometry.Western Blot and immunofluorescence assays were performed to evaluate DNA damage in ESCC cells post-irradiation.Adipocyte-derived exosomes were isolated by ultracentrifugation and identified by electron microscopy.A similar set of experiments was performed on ESCC cells to analyze cell survival,apoptosis,and DNA damage post-radiation exposure.Exosomes from adipose tissue and serum exosomes from ESCC patients pre-and post-radiotherapy were subjected to high-throughput miRNA-sequencing and validated using real-time quantitative polymerase chain reaction.The correlation between potential target miRNAs and the short-term prognosis of radiotherapy in ESCC was evaluated by receiver operating characteristic curve analysis.RESULTS Co-culturing adipocytes with ESCC cells enhanced radioresistance,as evidenced by increased colony formation.Adipocyte co-culture reduced ESCC cell apoptosis and DNA damage post-radiation.Adipocyte-derived exosomes similarly conferred radioresistance in ESCC cells,decreasing apoptosis and DNA damage post-irradiation.Highthroughput miRNA-sequencing identified miR-660-5p in serum and adipose tissue exosomes.Patients with high expression of serum exosome miR-660-5p showed poor prognosis after radiotherapy.CONCLUSION Adipocyte-derived exosomal miR-660-5p is a potential biomarker for evaluating radiotherapy efficacy in ESCC.

Clinical and endoscopic characteristics of colorectal traditional serrated adenomas with dysplasia/adenocarcinoma in a Korean population

BACKGROUND Traditional serrated adenoma(TSA)is a rare and precancerous lesion of colorectal cancer.The clinical and endoscopic differentiations between TSAs without dysplasia or adenocarcinoma(TSAOs)and TSAs with dysplasia or adenocarcinoma(TSADs)remain unclear.AIM To evaluate the characteristics of colorectal TSAs and compare the characteristics of TSAOs with those of TSADs.METHODS This retrospective study included 193 patients who underwent endoscopic resection and received a pathologic diagnosis of TSA.We reviewed the medical,endoscopic,and histopathologic records of patients who underwent endoscopic resection of TSAs between January 2010 and December 2023.RESULTS TSAs were more frequently located in the rectosigmoid colon.Most TSAs had 0-Ip,0-Isp,or 0-Is morphologies.The TSAD lesions were larger than TSAO lesions.TSAD lesions more commonly had a red color and an irregular border than TSAO lesions.TSAOs were usually treated using conventional endoscopic mucosal resection,whereas TSADs were treated using conventional endoscopic mucosal resection,endoscopic submucosal dissection,and surgery.Post-polypectomy bleeding was more common with TSADs than with TSAOs.Univariate analysis showed that gastrointestinal bleeding,red color,0-IIa,irregular border,and lobular mucosal surface were significantly associated with TSADs.Multivariate analysis showed that gastrointestinal bleeding,an irregular border,and a lobular mucosal surface were significantly associated with TSADs.CONCLUSION TSAs with gastrointestinal bleeding,an irregular border,and a lobular mucosal surface are associated with an increased risk of dysplasia or adenocarcinoma.

Five-year complete remission of super-giant hepatocellular carcinoma with hepatectomy followed by sorafenib plus camrelizumab:A case report

BACKGROUND Cirrhotic patients with super-giant hepatocellular carcinoma(HCC)and portal vein invasion generally have a poor prognosis.This paper presents a patient with super-giant HCC and portal vein invasion,who underwent hepatectomy followed by a combination of sorafenib and camrelizumab,resulting in complete remission(CR)for 5 years.CASE SUMMARY A 40-year-old male with compensated hepatitis B-related cirrhosis was diagnosed with HCC,Barcelona Clinic Liver Cancer stage C.Enhanced computed tomography imaging revealed a 152 mm×171 mm tumor in the right liver,invading the portal vein and hepatic vein.Liver function was normal.The patient successfully underwent hepatectomy on July 18,2019.However,by December 2019,HCC recurrence with lung metastases and portal vein invasion were detected.He started treatment with sorafenib(200 mg twice daily)and camrelizumab(200 mg every 3 weeks).By May 12,2020,the patient was confirmed to have CR.Camrelizumab was adjusted to 200 mg every 12 weeks from June 16,2021,with the last infusion on March 29,2024.Although no further tumor recurrence was observed,he experienced two episodes of gastrointestinal bleeding due to esophagogastric varices,which were managed with endoscopic therapy.To date,the patient has remained in CR for 5 years.CONCLUSION The combination of hepatectomy with sorafenib and camrelizumab can achieve durable CR in patients with supergiant HCC and portal vein invasion.Further research is necessary to address these challenges and improve patient outcomes.

CRAFITY score and nomogram predict the clinical efficacy of lenvatinib combined with immune checkpoint inhibitors in hepatocellular carcinoma

BACKGROUND The CRAFITY score is mainly utilized for hepatocellular carcinoma(HCC)patients receiving atezolizumab and bevacizumab,with little investigation in its predictive capacity for alternative regimens,such as lenvatinib and programmed cell death protein 1(PD-1)inhibitors,which are widely utilized in Chinese clinical practice.AIM To look at the predictive significance of the CRAFITY score in HCC patients taking lenvatinib and PD-1 inhibitors.METHODS The retrospective investigation consisted of 192 patients with incurable HCC who received lenvatinib and PD-1 inhibitors between January 2018 and January 2022.Patients were stratified according to CRAFITY score(based on baseline alphafetoprotein and C-reactive protein levels)into CRAFITY-low,CRAFITY-intermediate,and CRAFITY-high groups.Overall survival(OS)and progressionfree survival(PFS)were assessed using Kaplan-Meier analysis,and independent prognostic factors were identified through Cox regression analysis.Nomograms were created to forecast survival for a year.RESULTS The median PFS and OS were the longest for patients in the CRAFITY-low group,followed by those in the CRAFITY-intermediate and CRAFITY-high groups(median PFS:8.4 months,6.0 months,and 3.1 months,P<0.0001;median OS:33.4 months,19.2 months,and 6.6 months,P<0.0001).Both the objective response rate(5%,19.6%,and 22%,P=0.0669)and the disease control rate(50%,76.5%,and 80%,P=0.0023)were considerably lower in the CRAFITY-high group.The findings from the multivariate analysis showed that a nomogram which included the tumor number,prior transarterial chemoembolization history,and CRAFITY score predicted 12-month survival with an area under the curve of 0.788(95%confidence interval:0.718-0.859),which was in good agreement with actual data.CONCLUSION The CRAFITY score is a valuable predictor of survival and treatment outcomes in patients receiving lenvatinib and PD-1 inhibitors.

Nomogram based on a novel nutritional immune-inflammatory status score to predict postoperative outcomes in esophageal squamous cell carcinoma

BACKGROUND The relationship between patient nutritional,immune,and inflammatory status is linked to tumor progression and prognosis.However,there are limited studies on the prognosis of esophageal squamous cell carcinoma(ESCC)after surgery based on the comprehensive indicators of these factors.AIM To develop and validate a novel nomogram based on a nutritional immuneinflammatory status(NIIS)score for predicting postoperative outcomes in ESCC.METHODS This retrospective study examined 829 patients with ESCC who underwent radical surgery between June 2016 and June 2020,with 568 patients in the training cohort and 261 patients in the validation cohort.We incorporated comprehensive indicators related to nutrition,immunity,and inflammation to develop the NIIS score, using LASSO regression. Subsequently, a nomogram combining the NIIS score and other clinicopathologicalparameters was developed and validated using calibration curves, time-dependent area under curves, and decisioncurve analysis.RESULTSWe identified eight indicators that constitute the NIIS score. High-risk scores emerged as an independent riskfactor for overall survival [training set HR 2.497 (1.802, 3.458), P < 0.001]. A NIIS nomogram for personalizedprognostic prediction was developed by integrating the NIIS score with clinicopathological variables, yieldingenhanced predictive value relative to individual indicators and the UICC/TNM staging system.CONCLUSIONThe NIIS score provides strong predictive value for postoperative outcomes in ESCC, thus offering a valuable toolfor clinical decision-making.

Advancements and challenges in esophageal carcinoma prognostic models:A comprehensive review and future directions

In this article,we comment on the article published by Yu et al.By employing LASSO regression and Cox proportional hazard models,the article identified nine significant variables affecting survival,including body mass index,Karnofsky performance status,and tumor-node-metastasis staging.We firmly concur with Yu et al regarding the vital significance of clinical prediction models(CPMs),including logistic regression and Cox regression for assessment in esophageal carcinoma(EC).However,the nomogram's limitations and the complexities of integrating genetic factors pose challenges.The integration of immunological data with advanced statistics offers new research directions.High-throughput sequencing and big data,facilitated by machine learning,have revolutionized cancer research but require substantial computational resources.The future of CPMs in EC depends on leveraging these technologies to improve predictive accuracy and clinical application,addressing the need for larger datasets,patientreported outcomes,and regular updates for clinical relevance.

Efficacy of sorafenib combined with transarterial chemoembolization in the treatment of advanced hepatocellular carcinoma:A metaanalysis

BACKGROUND The combination of sorafenib with transarterial chemoembolization(TACE)is being investigated for its potential to improve outcomes in advanced hepatocellular carcinoma(HCC).AIM To evaluate the efficacy of this combined treatment strategy in enhancing overall survival(OS)and progression-free survival(PFS)compared to monotherapies.METHODS A systematic review was conducted following the PRISMA guidelines.A comprehensive search was performed across PubMed,EMBASE,Web of Science,and the Cochrane Library up to May 8,2024.Studies were included if they compared sorafenib plus TACE to sorafenib alone or TACE alone in adults with advanced HCC.Primary outcomes were OS,PFS,response rates,and safety profiles.Data extraction and quality assessment were independently performed by two reviewers.Heterogeneity was assessed using the I²statistic,and a random-effects model was applied for pooling data.Sensitivity analysis and publication bias assessment were also conducted.RESULTS A total of twelve studies involving 1174 patients met the inclusion criteria.Significant heterogeneity was observed for both OS(I²=72.6%,P<0.001)and PFS(I²=83.7%,P<0.001).The combined treatment of sorafenib with TACE significantly improved OS[hazard ratio(HR)=0.60,95%confidence interval(CI):0.44-0.76]and PFS(HR=0.54,95%CI:0.38-0.69).Sensitivity analysis confirmed the robustness of these findings.Funnel plots and Egger's test indicated no significant publication bias.CONCLUSION Sorafenib combined with TACE significantly enhances both OS and PFS in patients with advanced HCC compared to monotherapy.This combination therapy represents a promising approach to improving clinical outcomes in advanced liver cancer.

Transmembrane channel-like 5 drives hepatocellular carcinoma progression by regulating epithelial-mesenchymal transition

BACKGROUND Hepatocellular carcinoma(HCC)is a difficult cancer to manage due to its highly invasive and metastatic nature.AIM To investigate the molecular function of transmembrane channel-like 5(TMC5)in vitro and in vivo,with the objective of identifying novel diagnosis and treatment targets for HCC.METHODS The expression of TMC in cancer and normal tissues,along with its correlation with HCC prognosis,was analyzed using the GENT2,GEPIA database,and Human Protein Atlas.COX analysis was conducted to assess the relationship between TMC5 expression and overall survival in TCGA-LIHC patients.Further experiments were conducted to investigate the effect of TMC5 in cancer progression through loss-and gain-of-function assays in vitro and in vivo.RESULTS Bioinformatics revealed that TMC5 expression was generally higher in tumors than in normal tissues,and its expression was associated with poorer patient survival outcomes.TMC5 expression in HCC tissues and cells was consistent with the results of the bioinformatics analysis.Suppression of TMC5 expression reduced migration,invasion,and proliferation,while also decreasing the expression of epithelial-mesenchymal transition(EMT)-associated molecules in MHCC97-LM3 cells.Conversely,higher TMC5 expression significantly increased cell migration,invasion,proliferation,and EMT in MHCC97 L cells.TMC5 knockdown significantly decreased both the formation and spread of nodules in liver tissue,whereas TMC5 overexpression promoted them.CONCLUSION Our study provides compelling evidence that TMC5 is highly expressed in HCC and drives cancer progression through the activation of EMT-mediated invasion.TMC5 could represent a valuable molecular target for the diagnosis and treatment of HCC.

Anticipation for hepatic arterial infusion chemotherapy in the treatment of hepatocellular carcinoma

Hepatic arterial infusion chemotherapy (HAIC) is an advanced targeted therapeuticapproach for hepatocellular carcinoma (HCC), the most common type ofprimary liver cancer. HAIC has demonstrated significant potential in managingadvanced HCC, particularly in regions with high prevalence rates. Despite itspromise, several challenges and areas for future research remain. Clinical studieshave substantiated the efficacy of HAIC in enhancing survival outcomes forpatients with advanced hepatic carcinoma. Notably, combination therapiesinvolving immune checkpoint inhibitors, such as lenvatinib and programmeddeath-1 inhibitors, have shown substantial improvements in median overallsurvival and progression-free survival compared to systemic chemotherapy.These combination therapies have also exhibited superior response rates anddisease control, with manageable and often less severe adverse events relative tosystemic treatments. This article is based on the review by Zhou et al and aims todiscuss the current status and future directions in the treatment of HCC, emphasizingthe role of HAIC and its integration with novel therapeutic agents.

LncRNA PCAT6 promotes progression and metastasis of colonic neuroendocrine carcinoma via MAPK pathway

BACKGROUND Colonic neuroendocrine carcinomas(NECs)are highly malignant and invasive with poor prognosis.Long noncoding RNAs(LncRNAs)participate in the tumorigenesis and metastasis of multiple cancers AIM To detect the roles and mechanisms of lncRNA prostate cancer associated transcript 6(PCAT6)in the progression of colonic NEC.METHODS Human NEC and adjacent normal samples were collected for immunohistochemistry staining of CgA and real-time quantitative polymerase chain reaction(RT-qPCR)of PCAT6 mRNA level.Subcutaneous xenograft tumor model and lung metastasis model were established in nude mice.The lung tissues were stained by hematoxylin and eosin to assess pulmonary metastasis.The expression of epithelial-mesenchymal transition(EMT)-related markers and pathway-related genes was measured by RT-qPCR and western blotting.CD56 expression was assessed by immunofluorescence staining.The biological functions of PCAT6 were examined by cell counting kit-8,colony formation assays,Transwell assays and wound healing assays.The interaction between PCAT6 and its potential downstream target was verified by luciferase reporter assays.RESULTS LncRNA PCAT6 was upregulated in human NEC samples and LCC-18 cells,and its high expression was positively correlated with poor prognosis in patients with colonic NEC.Additionally,the expression of PCAT6 was positively associated with the proliferation,migration,invasion,and EMT of LCC-18 cells.Moreover,PCAT6 facilitated tumor growth,lung metastasis and EMT in xenografts.Mechanistically,PCAT6 promoted the activation of MAPK to enhance the EMT in colonic NEC by targeting miR-326.CONCLUSION In conclusion,lncRNA PCAT6 accelerates the process of colonic NEC by activating ERK/p38 MAPK signaling through targeting miR-326.These results might provide useful information for exploring the potential therapeutic targets in colonic NEC.