Comprehensive analysis of clinical and biological value of ING family genes in liver cancer

BACKGROUND Liver cancer(LIHC)is a malignant tumor that occurs in the liver and has a high mortality in cancer.The ING family genes were identified as tumor suppressor genes.Dysregulated expression of these genes can lead to cell cycle arrest,senescence and/or apoptosis.ING family genes are promising targets for anticancer therapy.However,their role in LIHC is still not well understood.AIM To have a better understanding of the important roles of ING family members in LIHC.METHODS A series of bioinformatics approaches(including gene expression analysis,genetic alteration analysis,survival analysis,immune infiltration analysis,prediction of upstream microRNAs(miRNAs)and long noncoding RNAs(lncRNAs)of ING1,and ING1-related gene functional enrichment analysis)was applied to study the expression profile,clinical relationship,prognostic significance and immune infiltration of ING in LIHC.The relationship between ING family genes expression and tumor associated immune checkpoints was investigated in LIHC.The molecular mechanism of ING1 mediated hepatocarcinogenesis was preliminarily discussed.RESULTS mRNA/protein expression of different ING family genes in LIHC was analyzed in different databases,showing that ING family genes were highly expressed in LIHC.In 47 samples from 366 LIHC patients,the ING family genes were altered at a rate of 13%.By comprehensively analyzing the expression,clinical pathological parameters and prognostic value of ING family genes,ING1/5 was identified.ING1/5 was related to poor prognosis of LIHC,suggesting that they may play key roles in LIHC tumorigenesis and progression.One of the target miRNAs of ING1 was identified as hsa-miR-214-3p.Two upstream lncRNAs of hsa-miR-214-3p,U91328.1,and HCG17,were identified.At the same time,we found that the expression of ING family genes was correlated with immune cell infiltration and immune checkpoint genes.CONCLUSION This study lays a foundation for further research on the potential mechanism and clinical value of ING family genes in the treatment and prognosis of LIHC.

MiRNA-145-5p inhibits gastric cancer progression via the serpin family E member 1-extracellular signal-regulated kinase-1/2 axis

BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.

Effect of screening colonoscopy frequency on colorectal cancer mortality in patients with a family history of colorectal cancer

BACKGROUND Colorectal cancer is a common malignant tumor in China,and its incidence in the elderly is increasing annually.Inflammatory bowel disease is a group of chronic non-specific intestinal inflammatory diseases,including ulcerative colitis and Crohn’s disease.We included the clinicopathological and follow-up data of patients with colorectal cancer who underwent laparoscopic colectomy or open colectomy at our Gastrointestinal Department between January 2019 and December 2022.Surgical indicators,oncological indicators,and survival rates were compared between the groups.The results of 104 patients who met the above criteria were extracted from the database(laparoscopic colectomy group=63,open colectomy group=41),and there were no statistically significant differences in the baseline data or follow-up time between the two groups.RESULTS Intraoperative blood loss,time to first ambulation,and time to first fluid intake were significantly lower in the laparoscopic colectomy group than in the open colectomy group.The differences in overall mortality,tumor-related mortality,and recurrence rates between the two groups were not statistically significant,and survival analysis showed that the differences in the cumulative overall survival,tumor-related survival,and cumulative recurrence-free rates between the two groups were not statistically significant.CONCLUSION In elderly patients with colorectal cancer,laparoscopic colectomy has better short-term outcomes than open colectomy,and laparoscopic colectomy has superior long-term survival outcomes compared with open colectomy.

Comprehensive analysis of distal-less homeobox family gene expression in colon cancer

BACKGROUND The distal-less homeobox(DLX)gene family plays an important role in the development of several tumors.However,the expression pattern,prognostic and diagnostic value,possible regulatory mechanisms,and the relationship between DLX family genes and immune infiltration in colon cancer have not been systematically reported.AIM We aimed to comprehensively analyze the biological role of the DLX gene family in the pathogenesis of colon cancer.METHODS Colon cancer tissue and normal colon tissue samples were collected from the Cancer Genome Atlas and Gene Expression Omnibus databases.Wilcoxon rank sum test and t-test were used to assess DLX gene family expression between colon cancer tissue and unpaired normal colon tissue.cBioPortal was used to analyze DLX gene family variants.R software was used to analyze DLX gene expression in colon cancer and the relationship between DLX gene family expression and clinical features and correlation heat map.The survival package and Cox regression module were used to assess the prognostic value of the DLX gene family.The pROC package was used to analyze the diagnostic value of the DLX gene family.R software was used to analyze the possible regulatory mechanisms of DLX gene family members and related genes.The GSVA package was used to analyze the relationship between the DLX gene family and immune infiltration.The ggplot2,the survminer package,and the clusterProfiler package were used for visualization.RESULTS DLX1/2/3/4/5 were significantly aberrantly expressed in colon cancer patients.The expression of DLX genes were associated with M stage,pathologic stage,primary therapy outcome,residual tumor,lymphatic invasion,T stage,N stage,age,perineural invasion,and history of colon polyps.DLX5 was independently correlated with the prognosis of colon cancer in multivariate analysis.DLX1/2/3/4/5/6 were involved in the development and progression of colon cancer by participating in immune infiltration and associated pathways,including the Hippo signaling pathway,the Wnt signaling pathway,several signaling pathways regulating the pluripotency of stem cells,and Staphylococcus aureus infection.CONCLUSION The results of this study suggest a possible role for the DLX gene family as potential diagnostic or prognostic biomarkers and therapeutic targets in colon cancer.

Diagnostic value of methylated branched chain amino acid transaminase 1/IKAROS family zinc finger 1 for colorectal cancer

BACKGROUND The diagnostic value of combined methylated branched chain amino acid transaminase 1(BCAT1)/IKAROS family zinc finger 1(IKZF1)in plasma for colorectal cancer(CRC)has been explored since 2015.Recently,several related studies have published their results and showed its diagnostic efficacy.AIM To analyze the diagnostic value of methylated BCAT1/IKZF1 in plasma for screening and postoperative follow-up of CRC.METHODS The candidate studies were identified by searching the PubMed,Embase,Cochrane Library,CNKI,and Wanfang databases from May 31,2003 to June 1,2023.Sensitivity,specificity,and diagnostic accuracy were calculated by merging ratios or means.RESULTS Twelve eligible studies were included in the analysis,involving 6561 participants.The sensitivity of methylated BCAT1/IKZF1 in plasma for CRC diagnosis was 60%[95%confidence interval(CI)53-67]and specificity was 92%(95%CI:90-94).The positive and negative likelihood ratios were 8.0(95%CI:5.8-11.0)and 0.43(95%CI:0.36-0.52),respectively.Diagnostic odds ratio was 19(95%CI:11-30)and area under the curve was 0.88(95%CI:0.85-0.91).The sensitivity and specificity for CRC screening were 64%(95%CI:59-69)and 92%(95%CI:91-93),respectively.The sensitivity and specificity for recurrence detection during follow-up were 54%CONCLUSION The detection of methylated BCAT1/IKZF1 in plasma,as a non-invasive detection method of circulating tumor DNA,has potential CRC diagnosis,but the clinical application prospect needs to be further explored.

Effectiveness of family psychosocial intervention on mental health and family function of caregivers of children with cancer:a meta-analysis

Objective:To evaluate the effect of family psychosocial intervention on the mental health and family function of caregivers of children with cancer.Methods:A comprehensive literature search of CNKI,Wanfang,VIP,CMB,PubMed,Web of Science,MEDLINE,Embase,Cochrane Library,and PsycARTICLES was conducted to retrieve randomized controlled trials of family psychosocial intervention from database inception until 19 September 2021.RevMan(version 5.4.1)was used to analyze the data.Results:A total of 894 caregivers participated in 11 studies.The analysis showed that anxiety(standardized mean difference[SMD]=−0.22,95%confidence interval[CI]=−0.37 to−0.07,P=0.004)and depression(SMD=−0.33,95%CI=−0.57 to−0.08,P=0.01)were significantly reduced,while family function(SMD=−0.86,95%CI=−1.28 to−0.45,P<0.001)was significantly improved by the family psychosocial intervention compared with the controls.According to subgroup analysis,family psychosocial interventions were found to reduce posttraumatic stress disorder(PTSD)symptoms when the follow-up time was>1 month(SMD=−0.48,95%CI=0.68 to−0.27,P<0.00001).Conclusions:Current evidence supports the use of family psychological intervention to reduce depression and anxiety and improve family function.However,its effect on PTSD symptoms requires further study.Future studies should further identify the role of specific family psychosocial interventions on families and caregivers of children with cancer.

Prioritizing the efforts:lived experiences of family when taking care of people with cancer

Objective:Cancer has one of the highest disease mortality rates.Families are very important in the treatment of people with cancer.By using a phenomenological design,this study aimed to explore the experience of families in caring for a person with cancer and to identify the needs of these families.Methods:First,eight interviews were under taken with family members selected through a purposive sampling method.Then,another three interviews were conducted for data validation.The collected data were analyzed using the framework method of analysis.Results:The core theme,“Prioritizing the efforts:Being aware of the best we could do for our family,”reflected family’s experiences of caring for a person with cancer and was underpinned by five themes:“Decisions to make,”“Keeping up the good support,”“Acknowledging the others’contributions,”“Assisting my family to alleviate the disease,”and“Adapting to the current situation.”Conclusions:The results suggest that building mutual trust and communication between family and healthcare professionals is vital in decision-making for people with cancer.Family may also work with the person in fulfilling their needs,without disregarding the needs of the family.When suppor ting the needs of people with diabetes,the family requires appropriate information,and thus,healthcare professionals wisely select which information can help the family make a decision regarding the treatment.After administering the treatment and providing information for people with cancer and their family,asking for feedback is required for evaluation.

Digestive and breast cancer patients managed during the first wave of COVID-19 pandemic:Short and middle term outcomes

BACKGROUND The first wave of coronavirus disease 2019(COVID-19)pandemic in Spain lasted from middle March to the end of June 2020.Spanish population was subjected to lockdown periods and scheduled surgeries were discontinued or reduced during variable periods.In our centre,we managed patients previously and newly diagnosed with cancer.We established a strategy based on limiting perioperative social contacts,preoperative screening(symptoms and reverse transcriptionpolymerase chain reaction)and creating separated in-hospital COVID-19-free pathways for non-infected patients.We also adopted some practice modifications(surgery in different facilities,changes in staff and guidelines,using continuously changing personal protective equipment…),that supposed new inconveniences.AIM To analyse cancer patients with a decision for surgery managed during the first wave,focalizing on outcomes and pandemic-related modifications.METHODS We prospectively included adults with a confirmed diagnosis of colorectal,oesophago-gastric,liver-pancreatic or breast cancer with a decision for surgery,regardless of whether they ultimately underwent surgery.We analysed short-term outcomes[30-d postoperative morbimortality and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection]and outcomes after 3 years(adjuvant therapies,oncological events,death,SARS-CoV-2 infection and vaccination).We also investigated modifications to usual practice.RESULTS From 96 included patients,seven didn’t receive treatment that period and four never(3 due to COVID-19).Operated patients:28 colon and 21 rectal cancers;laparoscopy 53.6%/90.0%,mortality 3.57%/0%,major complications 7.04%/25.00%,anastomotic leaks 0%/5.00%,3-years disease-free survival(DFS)82.14%/52.4%and overall survival(OS)78.57%/76.2%.Six liver metastases and six pancreatic cancers:no mortality,one major complication,three grade A/B liver failures,one bile leak;3-year DFS 0%/33.3%and OS 50.0%/33.3%(liver metastases/pancreatic carcinoma).5 gastric and 2 oesophageal tumours:mortality 0%/50%,major complications 0%/100%,anastomotic leaks 0%/100%,3-year DFS and OS 66.67%(gastric carcinoma)and 0%(oesophagus).Twenty breast cancer without deaths/major complications;3-year OS 100%and DFS 85%.Nobody contracted SARS-CoV-2 postoperatively.COVID-19 pandemic–related changes:78.2%treated in alternative buildings,43.8%waited more than 4 weeks,two additional colostomies and fewer laparoscopies.CONCLUSION Some patients lost curative-intent surgery due to COVID-19 pandemic.Despite practice modifications and 43.8%delays higher than 4 weeks,surgery was resumed with minimal changes without impacting outcomes.Clean pathways are essential to continue surgery safely.

Clinical and prognostic significance of expression of phosphoglycerate mutase family member 5 and Parkin in advanced colorectal cancer

BACKGROUND Drugs targeting mitochondria can induce mitophagy and restrain proliferation in colorectal cancer(CRC)cells.Phosphoglycerate mutase family member 5(PGAM5)activates serine/threonine PTEN-induced putative kinase 1/Parkin pathway-mediated mitophagy.However,there are few studies on the clinical and prognostic significance of expression of PGAM5 protein and mitophagy-related protein Parkin in patients.AIM To assess the clinical significance of PGAM5 and Parkin proteins,as biomarkers for diagnosis and prognosis of CRC,by studying their expression in advanced CRC tissues and their association with clinicopathological parameters.METHODS The expression of PGAM5 and Parkin in CRC tissues from 100 patients was determined by immunohistochemistry.Each case was evaluated by using a combined scoring method based on signal intensity staining(scored 0-3)and the proportion of positively stained cancer cells(scored 0-4).The final staining score was calculated as the intensity score multiplied by the proportion score.Specimens were categorized as either high or low expression according to the Youden index,and the association between the expression of PGAM5 or Parkin and clinicopathological factors was ascertained.Additionally,we employed western blot to measure PGAM5 and Parkin protein expression in six matched pairs of CRC and adjacent non-tumor tissues.RESULTS Immunohistochemical and western blot findings showed that both PGAM5 and Parkin protein expression in tumor tissues was significantly higher than that in the adjacent tissues:PGAM5 and Parkin were mainly expressed in the cytoplasm of colonic epithelial cells.PGAM5 and Parkin protein levels were significantly positively correlated in advanced CRC tissues.Moreover,reduced Parkin protein expression was an independent prognostic factor for overall survival and progression-free survival in CRC patients as evinced by multivariate analysis.CONCLUSION The expression of PGAM5 protein and mitophagy-related protein Parkin has diagnostic significance for CRC and may become new biomarkers.Parkin may be a potential marker for the survival of CRC patients.

Diagnostic value evaluation of trefoil factors family 3 for the early detection of colorectal cancer

AIM The purpose of this study was to evaluate the diagnostic value of trefoil factor family 3(TFF3) for the early detection of colorectal cancer(CC). METHODS Serum TFF3 and carcino-embryonic antigen(CEA) were detected in 527 individuals, including 115 healthy control(HC), 198 colorectal adenoma(CA), and 214 CC individuals in the training group. RESULTS Serum TFF3 showed no significant correlation with age, gender, or tumor location but showed significant correlation with the tumor stage. Serum TFF3 in the CC group was significantly higher than in the HC or CA group. The AUC values of TFF3 for discriminating between HC and CC and between CA and CC were 0.930(0.903, 0.958) and 0.834(0.796, 0.873). A multivariate model combining TFF3 and CEA was built. Compared to TFF3 or CEA alone, the multivariate model showed significant improvement(P < 0.001). For discriminating between HC and CC, HC and early stage CC, HC and advanced stage CC, CA and CC, CA and early stage CC, and CA and advanced stage CC in the training group, the sensitivities were 92.99%, 91.46%, 93.18%, 73.83%, 76.83%, and 81.82%, and the specificities were 91.30%, 91.30%, 93.91%, 88.38%, 77.27%, and 88.38%, respectively. After validation, the sensitivities were 89.39%, 85.71%, 90.79%, 72.73%, 71.43%, and 78.95%, and the specificities were 87.85%, 87.85%, 2.52%, 87.85%, 80.77%, and 87.50%, respectively. CONCLUSION The multivariate diagnostic model that included TFF3 and CEA showed significant improvement over the conventional biomarker CEA and might provide a potential method for the early detection of CC.

CMTM family proteins 1–8:roles in cancer biological processes and potential clinical value

The CKLF-like MARVEL transmembrane domain containing(CMTM)family of genes comprises CKLF and CMTM1–8(previously called chemokine-like factor superfamily 1–8,CKLFSF1–8).The CMTM family proteins contain a structurally conserved MAL and related proteins for vesicle trafficking and membrane linking(MARVEL)domain.Dysregulated expression of multiple CMTM family members is a common feature in many human cancer types.CMTM proteins control critical biological processes in cancer development,including growth factor receptor activation and recycling,cell proliferation,apoptosis,metastasis,and immune evasion.Emergingin vivo andin vitro evidence indicates that the mechanisms of action of most CMTM proteins are complex and multifactorial.This review highlights new findings regarding the roles of CMTM1–8 in cancer,particularly in tumor growth,metastasis,and immune evasion.Additionally,the potential clinical value of CMTMs as novel drug targets or biomarkers is discussed.

Treatment of Precancerous Lesions of the Cervix of the Uterus by Leep: Experience of the Principal Clinic of the Togolese Association of Family Well-Being Planning Center (ATBEF)

Objectives: Describe the socio-demographic characteristics, describe the main indications for LEEP and present the main complications. Methodology: This was a cross-sectional and descriptive study with consecutive recruitment of the study population through cervical cancer screening campaigns throughout the country during the period July 1, 2017 to April 30, 2019. Included were all patients eligible for LEEP and having benefited from this therapeutic method during our study period. Data were collected from a registry and recorded on a questionnaire developed for this study. These data were analyzed using Epi info 3.5.1 software. The following parameters were studied: patient age, indication for LEEP, intraoperative and postoperative complications, histological examination of the specimens, and postoperative surveillance and screening follow-up one year after LEEP. Results: During the study period, 12,595 women were screened for precancerous cervical lesions. A total of 474 women had precancerous lesions. Of these women, 227 had undergone loop resection, a rate of 47.9%. The main indications for LEEP were extensive lesions (68.7%), lesions penetrating the internal cervical os (12.8%). Incidents occurred in 7.5% of patients during the procedure. Post-operative complications occurred in 14.7% of cases. Conclusion: LEEP is a better way to treat precancerous lesions but is not well known by medical staff. The equipment of health facilities and the training of medical staff will make it possible to popularize the practice throughout the country. This extension will contribute to the fight against cervical cancer.

Family resilience of cancer patients:a concept analysis

Objective:The concept of family resilience of cancer patients was discussed through literature review,which provided reference for nursing of cancer patients.Methods:China National Knowledge Infrastructure(CNKI),Wanfang Database,SinoMed,PubMed,Web of Science,and Embase were systematically searched,and the concept analysis method proposed by Walker and Avant was adopted.Results:In this study,we defined the concept of family resilience,identified attributes,and analyzed the antecedents and consequences.The proposed operational definition of family resilience was:After a family member is diagnosed with cancer,the whole family can actively explore its own unique internal and external resources and advantages,strengthen self-regulation,jointly cope with the crisis by establishing close family relationships,providing mutual support to family members,and interacting with the outside world.Conclusions:The definition of family resilience of cancer patients is conducive to the development of measurement tools and the improvement of family outcomes of adult cancer patients by intervening family resilience factors.

Secretome-microRNA and anti-proliferative APRO family proteins as cancer prevention and stem cell research strategies

Stemness of cancer cells contains limitless self-renewal proliferation.For the purpose of proliferation,secretome might exert its effects via the paracrine signaling.Specific microRNAs enclosed in the secretome of cancer stem cells could regulate the expression of anti-proliferative APRO family proteins.The biological functions of APRO family proteins seems to be quite intricate,however,which might be a key modulator of microRNAs,then could regulate the proliferation of cancer cells.In addition to affecting proliferation/differentiation during cellular development,APRO family proteins might also play an imperious role on keeping homeostasis in healthy stem cells under a physiological condition.Therefore,relationship between the microRNAs and the APRO family proteins has attracted much attention in the field of cancer research and regenerative medicine.Here,we have described the molecular mechanism behind this interplay that have a potential role in the future promising tools with targeting APRO family proteins for the medical applications.

MiR-16-5p plays an inhibitory role in human non-small cell lung cancer through Fermitin family member 2

Increasing evidence indicates that aberrant expressions of some microRNAs are associated with cancer progression.However,the roles and biological mechanisms of miRNA-16-5p in human non-small cell lung cancer(NSCLC)are not to be well studied.Here,we validated that the expression of miR-16-5p was decreased significantly in NSCLC samples and cell lines.The correlation between the clinicopathological features of NSCLC and the miR-16-5p expression showed that the expression of miR-16-5p in non-small cell lung cancer was linked with the advanced TNM stage,positive lymph node metastasis,with short overall survival(OS).Also,a negative correlation between miR-16-5p and Fermitin family member 2(FERMT2)was observed,implying there may be a potential link about their regulation.The hypothesis was further confirmed by in-silico analysis and dual-luciferase reporter assay.Moreover,we demonstrated that the transfections of miR-16-5p mimics could alter some biological characteristics of NSCLC cells remarkably accomplished by the expression variance of FERMT2 in vitro and in vivo assays.Summarily,this study demonstrated that miR-16-5p,as a tumor suppression factor in NSCLC by targeting FERMT2,could serve as one promising biomarker in the prediction for NSCLC patients.

Understanding the role of transmembrane 9 superfamily member 1 in bladder cancer pathogenesis

In this editorial we comment on the article by Wei et al,published in the recent issue of the World Journal of Clinical Oncology.The authors investigated the role of Transmembrane 9 superfamily member 1(TM9SF1)protein in bladder cancer(BC)carcinogenesis.Lentiviral vectors were used to achieve silencing or overexpression of TM9SF1 gene in three BC cell lines.These cell lines were then subject to cell counting kit 8,wound-healing assay,transwell assay,and flow cytometry.Proliferation,migration,and invasion of BC cells were increased in cell lines subjected to TM9SF1 overexpression.TM9SF1 silencing inhibited proliferation,migration and invasion of BC cells.The authors conclude that TM9SF1 may be an oncogene in bladder cancer pathogenesis.

Treatment-induced neuroendocrine prostate cancer and de novo neuroendocrine prostate cancer:Identification,prognosis and survival,genetic and epigenetic factors

Neuroendocrine prostate cancer(NEPC)shows an aggressive behavior compared to prostate cancer(PCa),also known as prostate adenocarcinoma.Scanty foci in PCa can harbor genetic alternation that can arise in a heterogeneity of prostate cancer.NEPC may arise de novo or develop following androgen deprivation therapy(ADT).NEPC that arise following ADT has the nomenclature“treatmentemerging/induced NEPC(t-NEPC)”.t-NEPC would be anticipated in castration resistant prostate cancer(CRPC)and metastatic PCa.t-NEPC is characterized by low or absent androgen receptor(AR)expression,independence of AR signaling,and gain of neuroendocrine phenotype.t-NEPC is an aggressive metastatic tumor,develops from PCa in response to drug induced ADT,and shows very short response to conventional therapy.t-NEPC occurs in 10%-17%of patients with CRPC.De novo NEPC is rare and is accounting for less than 2%of all PCa.The molecular mechanisms underlying the trans-differentiation from CRPC to t-NEPC are not fully elucidated.Sphingosine kinase 1 plays a significant role in t-NEPC development.Although neuroendocrine markers:Synaptophysin,chromogranin A,and insulinoma associated protein 1(INSM1)are expressed in t-NEPC,they are non-specific for diagnosis,prognosis,and follow-up of therapy.t-NEPC shows enriched genomic alteration in tumor protein P53(TP53)and retinoblastoma 1(RB1).There are evidences suggest that t-NEPC might develop through epigenetic evolution.There are genomic,epigenetic,and transcriptional alterations that are reported to be involved in development of t-NEPC.Knock-outs of TP53 and RB1 were found to contribute in development of t-NEPC.PCa is resistant to immunotherapy,and at present there are running trials to approach immunotherapy for PCa,CRPC,and t-NEPC.

Quantitative risk of positive family history in developing colorectal cancer: A meta-analysis

BACKGROUND Positive family history is a risk factor for development of colorectal cancer.Despite numerous studies on the topic,the absolute risk in patients with a positive family history remains unclear and therefore studies are lacking to validate non-invasive screening methods in individuals with positive family history.AIM To quantify the risk of colorectal cancer in individuals with a positive family history.METHODS A comprehensive electronic literature search was performed using PubMed from January 1955 until November 2017,EMBASE from 1947 until 2018,and Cochrane Library without date restrictions.Two independent reviewers conducted study selection,data extraction and quality assessment.A meta-analysis of Mantel-Haenzel relative risks was performed using the random effects model.Newcastle-Ottawa scale was used to score the quality of selected papers.Funnel plot and Egger’s regression test was performed to detect publication bias.Subgroup analysis was performed comparing Asian and non-Asian studies.Sensitivity analyses were performed to rule out the effect of the timing of the study,overall quality,the main outcome and the effect of each individual study in overall result.RESULTS Forty-six out of 3390 studies,including 906981 patients were included in the final analysis.41 of the included studies were case-control and 5 were cohort.A positive family history of colorectal cancer in first-degree relatives was associated with significantly increased risk of colorectal cancer with a relative risk of 1.87(95%CI:1.68-2.09;P<0.00001).Cochrane Q test was significant(P<0.00001,I2=90%).Egger’s regression test showed asymmetry in the funnel plot and therefore the Trim and Fill method was used which confirmed the validity of the results.There was no difference between Asian versus non-Asian studies.Results remained robust in sensitivity analyses.CONCLUSION Individuals with a positive family history of colorectal cancer are 1.87 times more likely to develop colorectal cancer.Screening guidelines should pay specific attention to individuals with positive family history and further studies need to be done on validating current screening methods or developing new modalities in this high-risk population.

Global whole family based-Helicobacter pylori eradication strategy to prevent its related diseases and gastric cancer

Helicobacter pylori (H.pylori) infects approximately 50% of the world population.The multiple gastrointestinal and extra-gastrointestinal diseases caused by H.pylori infection pose a major healthcare threat to families and societies;it is also a heavy economic and healthcare burden for countries that having high infection rates.Eradication of H.pylori is recommended for all infected individuals.Traditionally,"test and treat"and"screen and treat"strategies are available for various infected populations.However,clinical practice has noticed that these strategies have some shortfalls and may need refinement,mostly due to the fact that they are not easily manageable,and are affected by patient compliance,selection of treatment population and cost-benefit estimations.Furthermore,it is difficult to control infections from the source,therefore,development of additional,compensative strategies are encouraged to solve the above problems and facilitate bacteria eradication.H.pylori infection is a family-based disease,but few studies have been performed in a whole family-based approach to curb its intra-familial transmission and the development of related diseases.In this work,a third,novel whole family-based H.pylori eradication strategy is introduced.This approach screens,identifies,treats and follows up on all H.pylori-infected individuals in entire families to control H.pylori infection among family members,and reduce its long-term complications.This strategy is high-risk population-oriented,and able to reduce H.pylori spread among family members.It also has good patient-family compliance and,importantly,is practical for both high and low H.pylori-infected communities.Future efforts in these areas will be critical to initiate and establish healthcare policies and management strategies to reduce H.pylori-induced disease burden for society.

Vestigial like family member 3 is a novel prognostic biomarker for gastric cancer

BACKGROUND Vestigial like family member 3(VGLL3)is associated with the prognosis of epithelial ovarian cancer and soft tissue sarcoma,but its role in gastric cancer(GC)is unclear.AIM To explore the expression pattern and clinical significance of VGLL3 in GC.METHODS Integrative analysis was performed on the GC transcriptome profiles and survival information deposited in the ONCOMINE,GEPIA,and ONCOLNC databases.The expression levels of VGLL3 mRNA and protein were analyzed in the freshly resected tumor and normal gastric tissues from GC patients by quantitative RT-PCR and Western blot,respectively.In addition,the in situ expression of VGLL3 in the GC tissues was determined by immunohistochemistry(IHC),and the patients were accordingly classified into the high and low expression groups.The correlation of VGLL3 expression status with patient prognosis was then determined by univariate and multivariate Cox regression analyses.RESULTS Analysis of the ONCOMINE and GEPIA databases showed that VGLL3 was significantly up-regulated in GC tissues(P=0.003),and associated with the tumor TNM stage(P=0.0163).The high VGLL3 expression group had a significantly worse prognosis compared to the low expression group,as per both GEPIA(P=0.0057)and ONCOLNC(P=0.01).The bioinformatics results were validated by the significantly higher VGLL3 mRNA and protein levels in the GC tissues compared to the adjacent normal tissues(P<0.001)in a cohort of 30 GC patients.Furthermore,high in situ expression of VGLL3 protein was associated with more advanced N and TNM stages and HER2 mutation(P<0.05)in a cohort of 172 patients.Kaplan-Meier analysis showed that the high VGLL3 expression group had a worse prognosis compared to the low expression group(P=0.019).Multivariate analysis showed that VGLL3 expression status was an independent risk factor for prognosis.In addition,the prognostic risk model nomogram showed that VGLL3 was the most important indicator,with an area under the receiver operating characteristic(ROC)curve(AUC)of 0.613 for 3-year survival and 0.706 for 5-year survival.Finally,the protein interaction network analysis revealed that VGLL3 is likely involved in the Hippo signaling pathway.CONCLUSION VGLL3 is overexpressed in GC tissues and associated with a poor prognosis,indicating its potential as a novel prognosis biomarker and therapeutic target for GC.