Transcriptome sequencing reveals novel biomarkers and immune cell infiltration in esophageal tumorigenesis

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the critical regulators and underlying molecular mechanisms remain largely unknown.AIM To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention.METHODS A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide(4NQO)to C57BL/6 mice.Moreover,we established a control group without 4NQO treatment of mice.Then,transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses,including low-grade IN(LGIN),high-grade IN(HGIN),and CA,and controlled normal tissue(NOR)samples.Differentially expressed genes(DEGs)were identified in the LGIN,HGIN,and CA groups,and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The CIBERSORT algorithm was used to detect the pattern of immune cell infilt-ration.Immunohistochemistry(IHC)was also conducted to validate our results.Finally,the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice.RESULTS Compared with those in the NOR group,a total of 681541,and 840 DEGs were obtained in the LGIN,HGIN,and CA groups,respectively.Using the intersection of the three sets of DEGs,we identified 86 genes as key genes involved in the development of ESCC.Enrichment analysis revealed that these genes were enriched mainly in the keratinization,epidermal cell differentiation,and interleukin(IL)-17 signaling pathways.CIBERSORT analysis revealed that,compared with those in the NOR group,M0 and M1 macrophages in the 4NQO group showed stronger infiltration,which was validated by IHC.Serum cytokine analysis revealed that,compared with those in the NOR group,IL-1βand IL-6 were upregulated,while IL-10 was downregulated in the LGIN,HGIN,and CA groups.Moreover,the expression of the representative key genes,such as S100a8 and Krt6b,was verified in external human samples,and the results of immunohistochemical staining were consistent with the findings in mice.CONCLUSION We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions.In addition,we found that macrophage infiltration and abnormal alterations in the levels of inflam-mation-associated cytokines,such as IL-1β,IL-6,and IL-10,in the peripheral blood may be closely associated with the development of ESCC.

Ferroptosis biomarkers predict tumor mutation burden's impact on prognosis in HER2-positive breast cancer

BACKGROUND Ferroptosis has recently been associated with multiple degenerative diseases.Ferroptosis induction in cancer cells is a feasible method for treating neoplastic diseases.However,the association of iron proliferation-related genes with prognosis in HER2+breast cancer(BC)patients is unclear.AIM To identify and evaluate fresh ferroptosis-related biomarkers for HER2+BC.METHODS First,we obtained the mRNA expression profiles and clinical information of HER2+BC patients from the TCGA and METABRIC public databases.A four gene prediction model comprising PROM2,SLC7A11,FANCD2,and FH was subsequently developed in the TCGA cohort and confirmed in the METABRIC cohort.Patients were stratified into high-risk and low-risk groups based on their median risk score,an independent predictor of overall survival(OS).Based on these findings,immune infiltration,mutations,and medication sensitivity were analyzed in various risk groupings.Additionally,we assessed patient prognosis by combining the tumor mutation burden(TMB)with risk score.Finally,we evaluated the expression of critical genes by analyzing single-cell RNA sequencing(scRNA-seq)data from malignant vs normal epithelial cells.RESULTS We found that the higher the risk score was,the worse the prognosis was(P<0.05).We also found that the immune cell infiltration,mutation,and drug sensitivity were different between the different risk groups.The highrisk subgroup was associated with lower immune scores and high TMB.Moreover,we found that the combination of the TMB and risk score could stratify patients into three groups with distinct prognoses.HRisk-HTMB patients had the worst prognosis,whereas LRisk-LTMB patients had the best prognosis(P<0.0001).Analysis of the scRNAseq data showed that PROM2,SLC7A11,and FANCD2 were significantly differentially expressed,whereas FH was not,suggesting that these genes are expressed mainly in cancer epithelial cells(P<0.01).CONCLUSION Our model helps guide the prognosis of HER2+breast cancer patients,and its combination with the TMB can aid in more accurate assessment of patient prognosis and provide new ideas for further diagnosis and treatment.

Circulating tumor cells as potential prognostic biomarkers for earlystage pancreatic cancer:A systematic review and meta-analysis

BACKGROUND Pancreatic cancer is difficult to be diagnosed early clinically,while often leads to poor prognosis.If optimal personalized treatment plan can be provided to pancreatic cancer patient at an earlier stage,this can greatly improve overall survival(OS).Circulating tumor cells(CTCs)are a collective term for various types of tumor cells present in the peripheral blood(PB),which are formed by detachment during the development of solid tumor lesions.Most CTCs undergo apoptosis or are phagocytosed after entering the PB,whereas a few can escape and anchor at distal sites to develop metastasis,increasing the risk of death for patients with malignant tumors.AIM To investigate the significance of CTCs in predicting the prognosis of early pancreatic cancer patients.METHODS The PubMed,EMBASE,Web of Science,Cochrane Library,China National Knowledge Infrastructure,China Biology Medicine,and ChinaInfo databases were searched for articles published through December 2022.Studies were considered qualified if they included patients with early pancreatic cancer,analyzed the prognostic value of CTCs,and were full papers reported in English or Chinese.Researches were selected and assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol and the Newcastle-Ottawa Scale criteria.We used a funnel plot to assess publication bias.RESULTS From 1595 publications,we identified eight eligible studies that collectively enrolled 355 patients with pancreatic cancer.Among these original studies,two were carried out in China;three in the United States;and one each in Italy,Spain,and Norway.All eight studies analyzed the relevance between CTCs and the prognosis of patients with early-stage pancreatic cancer after surgery.A meta-analysis showed that the patients that were positive pre-treatment or post-treatment for CTCs were associated with decreased OS[hazard ratio(HR)=1.93,95% confidence interval(CI):1.197-3.126,P=0.007]and decreased relapse-free/disease-free/progressionfree survival(HR=1.27,95%CI:1.137-1.419,P<0.001)in early-stage pancreatic cancer.Additionally,the results suggest no statistically noticeable publication bias for overall,disease-free,progression-free,and recurrence-free survival.CONCLUSION This pooled meta-analysis shows that CTCs,as biomarkers,can afford reliable prognostic information for patients with early-stage pancreatic cancer and help develop individualized treatment plans.

IGF2BPs: a family as diagnostic and prognostic biomarkers in digestive system tumors

The highest morbidity and mortality in the world are attributed to digestive system tumors,such as stomach cancer,liver cancer,and pancreatic cancer.Exploring potential biomarkers is a crucial direction of tumor research.We use bioinformatics methods to explore potential biomarkers of the digestive system.Mining and analyzing data from Gene Expression Profiling Interactive Analysis(GEPIA),Kaplan-Meier,cBioPortal,and Metabolic gEne RApid Visualizer(MERAV)to explore the correlation between IGF2BP(insulin-like growth factor-2 mRNA-binding protein)family expression and immune infiltration in digestive system tumors,and further probe the prognostic value of IGF2BP family in digestive system tumors.Esophageal cancer tissues showed a significantly higher expression of IGF2BP2 than normal tissues,while IGF2BP3 was notably more expressed in esophageal cancer,pancreatic cancer,and stomach cancer.In the prognosis evaluation,the IGF2BP1 gene in patients with liver cancer and the IGF2BP2 and IGF2BP3 genes in patients with stomach cancer and liver cancer of the low gene expression level groups were better.Multivariate COX regression analysis further suggested that tumor stage,CD8 positive T cells,macrophages,dendritic cell infiltration,and IGF2BP3 expression were independent risk factors affecting the prognosis of patients with stem cell liver cancer.The IGF2BP family may be a potential marker for immunotherapy and the prognosis of digestive system tumors.

Proteomics-based identification of proteins in tumor-derived exosomes as candidate biomarkers for colorectal cancer

BACKGROUND Colorectal cancer(CRC)is the second leading cause of cancer-related death,with high morbidity worldwide.There is an urgent need to find reliable diagnostic biomarkers of CRC and explore the underlying molecular mechanisms.Exosomes are involved in intercellular communication and participate in multiple pathological processes,serving as an important part of the tumor microenvironment.AIM To investigate the proteomic characteristics of CRC tumor-derived exosomes and to identify candidate exosomal protein markers for CRC.METHODS In this study,10 patients over 50 years old who were diagnosed with moderately differentiated adenocarcinoma were recruited.We paired CRC tissues and adjacent normal intestinal tissues(>5 cm)to form the experimental and control groups.Purified exosomes were extracted separately from each tissue sample.Data-independent acquisition mass spectrometry was implemented in 8 matched samples of exosomes to explore the proteomic expression profiles,and differentially expressed proteins(DEPs)were screened by bioinformatics analysis.Promising exosomal proteins were verified using parallel reaction monitoring(PRM)analysis in 10 matched exosome samples.RESULTS A total of 1393 proteins were identified in the CRC tissue group,1304 proteins were identified in the adjacent tissue group,and 283 proteins were significantly differentially expressed between them.Enrichment analysis revealed that DEPs were involved in multiple biological processes related to cytoskeleton construction,cell movement and migration,immune response,tumor growth and telomere metabolism,as well as ECM-receptor interaction,focal adhesion and mTOR signaling pathways.Six differentially expressed exosomal proteins(NHP2,OLFM4,TOP1,SAMP,TAGL and TRIM28)were validated by PRM analysis and evaluated by receiver operating characteristic curve(ROC)analysis.The area under the ROC curve was 0.93,0.96,0.97,0.78,0.75,and 0.88(P<0.05)for NHP2,OLFM4,TOP1,SAMP,TAGL,and TRIM28,respectively,indicating their good ability to distinguish CRC tissues from adjacent intestinal tissues.CONCLUSION In our study,comprehensive proteomic profiles were obtained for CRC tissue exosomes.Six exosomal proteins,NHP2,OLFM4,TOP1,SAMP,TAGL and TRIM28,may be promising diagnostic markers and effective therapeutic targets for CRC,but further experimental investigation is needed.

Predictive values of multidetector-row computed tomography combined with serum tumor biomarkers in preoperative lymph node metastasis of gastric cancer

Objective: Multidetector-row computed tomography(MDCT) and serum tumor biomarkers are commonly used to evaluate the preoperative lymph node metastasis and the clinical staging of gastric cancer(GC). This study intends to evaluate the clinical predictive value of MDCT and serum tumor biomarkers in lymph node metastasis of GC.Methods: The clinicopathologic data of 445 GC patients who underwent radical gastrectomy were retrospectively analyzed to evaluate the diagnostic value of MDCT and serum tumor biomarkers in lymph node metastatic staging of GC before surgery.Results: With the multinomial logistic regression analysis, the independent relative factors of lymph node metastasis of GC were identified as tumor size, depth of tumor invasion, vessel invasion, vascular embolus, and soft tissue invasion. The optimal critical value of the short diameter of lymph nodes detected by MDCT scanning for evaluation of preoperative lymph node metastasis was 6.0 mm, with 75.7% as predictive accuracy of lymph node metastasis compared to the postoperative pathological results of GC patients. In addition, the critical value of the short diameter of lymph nodes combined with serum tumor biomarkers [including carbohydrate antigen(CA)-724 and CA-199] could show an enhancement of predictive sensitivity of lymph node metastasis(up to 89.3%) before surgery.Conclusions: MDCT combined with serum tumor biomarkers should be adopted to improve preoperative sensitivity and accuracy of lymph node metastasis for GC patients.

Pancreatic neuroendocrine tumors:A review of serum biomarkers,staging,and management

Pancreatic neuroendocrine tumors(pNETs)are a heterogeneous group of tumors with complicated treatment options that depend on pathological grading,clinical staging,and presence of symptoms related to hormonal secretion.With regard to diagnosis,remarkable advances have been made:Chromogranin A is recommended as a general marker for pNETs.But other new biomarker modalities,like circulating tumor cells,multiple transcript analysis,microRNA profile,and cytokines,should be clarified in future investigations before clinical application.Therefore,the currently available serum biomarkers are insufficient for diagnosis,but reasonably acceptable in evaluating the prognosis of and response to treatments during follow-up of pNETs.Surgical resection is still the only curative therapeutic option for localized pNETs.However,a debulking operation has also been proven to be effective for controlling the disease.As for drug therapy,steroids and somatostatin analogues are the first-line therapy for those with positive expression of somatostatin receptor,while everolimus and sunitinib represent important progress for the treatment of patients with advanced pNETs.Great progress has been achieved in the combination of systematic therapy with local control treatments.The optimal timing of local control intervention,planning of sequential therapies,and implementation of multidisciplinary care remain pending.

Investigation of Combining Serum Tumor Biomarkers and Clinical Features for Elderly Lung Cancer Diagnosis and Classification

To evaluate the diagnosis model of serum tumor biomarker and several clinical features diagnose and classification for lung cancer, the solid protein chip technology (C-12) was used to detect the biomarkers of SF, CEA, CA242, NSE, CA125, CA19-9 and CA15-3 in serum and several clinical features of tumors and benign disease in elderly lung cancer patients were collected. Set up a discriminating analysis as a function diagnostic model in clinical elderly lung cancer diagnosis and sub-type discrimination. In combination of 2 obvious clinical indicators and 2 serum markers, it is possible to provide a diagnosis tool for lung cancer. With the help of mathematic model, it is promising to reduce the misjudgment risk based on the previous experience and therefore establish a reliable diagnosing function. This model is simple, cost-effective and easy to adapt in practice, and can also be used in screening of large population.

Correlation of tumor-associated macrophage density and proportion of M2 subtypes with the pathological stage of colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a prevalent global malignancy with complex prognostic factors.Tumor-associated macrophages(TAMs)have shown paradoxical associations with CRC survival,particularly concerning the M2 subset.AIM We aimed to establish a simplified protocol for quantifying M2-like TAMs and explore their correlation with clinicopathological factors.METHODS A cross-sectional study included histopathological assessment of paraffinembedded tissue blocks obtained from 43 CRC patients.Using CD68 and CD163 immunohistochemistry,we quantified TAMs in tumor stroma and front,focusing on M2 proportion.Demographic,histopathological,and clinical parameters were collected.RESULTS TAM density was significantly higher at the tumor front,with the M2 proportion three times greater in both zones.The tumor front had a higher M2 proportion,which correlated significantly with advanced tumor stage(P=0.04),pathological nodal involvement(P=0.04),and lymphovascular invasion(LVI,P=0.01).However,no significant association was found between the M2 proportion in the tumor stroma and clinicopathological factors.CONCLUSION Our study introduces a simplified protocol for quantifying M2-like TAMs in CRC tissue samples.We demonstrated a significant correlation between an increased M2 proportion at the tumor front and advanced tumor stage,nodal involvement,and LVI.This suggests that M2-like TAMs might serve as potential indicators of disease progression in CRC,warranting further investigation and potential clinical application.

Prognostic and predictive blood biomarkers in gastric cancer and the potential application of circulating tumor cells

Gastric cancer(GC), with its high incidence and mortality rates, is a highly fatal cancer that is common in East Asia particularly in China. Its recurrence and metastasis are the main causes of its poor prognosis. Circulating tumor cells(CTCs) or other blood biomarkers that are released into the circulating blood stream by tumors are thought to play a crucial role in the recurrence and metastasis of gastric cancer. Therefore, the detection of CTCs and other blood biomarkers has an important clinical significance; in fact, they can help predict the prognosis, assess the staging, monitor the therapeutic effects and determine the drug susceptibility. Recent research has identified many blood biomarkers in GC, such as various serum proteins, autoantibodies against tumor associated antigens, and cell-free DNAs. The analysis of CTCs and circulating cell-free tumor DNA(ctDNA) in the peripheral blood of patients with gastric cancer is called as liquid biopsy. These blood biomarkers provide the disease status for individuals and have clinical meaning. In this review, we focus on the recent scientific advances regarding CTCs and other blood biomarkers, and discuss their origins and clinical meaning.

Ipsilateral breast tumor recurrence in early stage breast cancer patients treated with breast conserving surgery and adjuvant radiation therapy: Concordance of biomarkers and tumor location from primary tumor to in-breast tumor recurrence

BACKGROUND Patients with an in-breast tumor recurrence(IBTR)after breast-conserving therapy have a high risk of distant metastasis and disease-related mortality.Classifying clinical parameters that increase risk for recurrence after IBTR remains a challenge.AIM To describe primary and recurrent tumor characteristics in patients who experience an IBTR and understand the relationship between these characteristics and disease outcomes.METHODS Patients with stage 0-II breast cancer treated with lumpectomy and adjuvant radiation were identified from institutional databases of patients treated from 2003-2017 at our institution.Overall survival(OS),disease-free survival,and local recurrence-free survival(LRFS)were estimated using the Kaplan Meier method.We identified patients who experienced an isolated IBTR.Concordance of hormone receptor status and location of tumor from primary to recurrence was evaluated.The effect of clinical and treatment parameters on disease outcomes was also evaluated.RESULTS We identified 2164 patients who met the eligibility criteria.The median follow-up for all patients was 3.73[interquartile range(IQR)2.27-6.07]years.Five-year OS was 97.7%(95%CI:96.8%-98.6%)with 28 deaths;5-year LRFS was 98.0%(97.2-98.8)with 31 IBTRs.We identified 37 patients with isolated IBTR,19(51.4%)as ductal carcinoma in situ and 18(48.6%)as invasive disease,of whom 83.3%had an in situ component.Median time from initial diagnosis to IBTR was 1.97(IQR:1.03-3.5)years.Radiotherapy information was available for 30 of 37 patients.Median whole-breast dose was 40.5 Gy and 23 patients received a boost to the tumor bed.Twenty-five of thirty-two(78.1%)patients had concordant hormone receptor status,HER-2 receptor status,and estrogen receptor(ER)(P=0.006)and progesterone receptor(PR)(P=0.001)status from primary to IBTR were significantly associated.There were no observed changes in HER-2 status from primary to IBTR.The concordance between quadrant of primary to IBTR was 10/19[(62.2%),P=0.008].Tumor size greater than 1.5 cm(HR=0.44,95%CI:0.22-0.90,P=0.02)and use of endocrine therapy upfront(HR=0.36,95%CI:0.18-0.73,P=0.004)decreased the risk of IBTR.CONCLUSION Among patients with early stage breast cancer who had breast conserving surgery treated with adjuvant RT,ER/PR status and quadrant were highly concordant from primary to IBTR.Tumor size greater than 1.5 cm and use of adjuvant endocrine therapy were significantly associated with decreased risk of IBTR.

Circulating tumor cells with epithelial-mesenchymal transition markers as potential biomarkers for the diagnosis of lung cancer

BACKGROUND Circulating tumor cells(CTCs) can be clustered into three subtypes according to epithelial-mesenchymal transition(EMT) markers: CTCs with epithelial markers(E-CTCs), CTCs with mesenchymal markers(M-CTCs), and CTCs with both markers(E&M-CTCs). CTC detection has clinical implications in the diagnosis of lung cancer(LC).AIM To clarify the diagnostic value of CTCs categorized by EMT markers in LC.METHODS The study included 106 patients with lung adenocarcinoma, including 42 groundglass opacities(GGO) and 64 solid lesions, who underwent surgery between July 2015 and December 2019. Eleven patients with benign tumors and seventeen healthy controls were included. CTCs in peripheral blood and associated EMT markers were detected preoperatively using the CanPatrol TM technique. The diagnostic power of CTCs for discriminating LC cases from controls was analyzed by the receiver operating characteristic(ROC) curve. The CytoploRare technique was used in 20 cases and 18 controls for validation, and Kappa values were calculated to evaluate consistency between techniques.RESULTS Of the 106 LC cases, 94(89.6%) had at least one CTC. CTCs were detectable in 35(83.3%) of 42 GGO cases. Total CTCs and E&M-CTCs were significantly more frequent in LC cases than in benign or healthy controls. The proportion of MCTCs plus E&M-CTCs increased gradually from healthy controls, to benign controls, to LC cases. The area under the ROC curve of total CTCs and E&M-CTCs was > 0.8 and > 10.75, respectively. The combined sensitivity of total-CTCs and E&M-CTCs was 85.85% for LC patients(80.95% for GGO patients) and the specificity was 78.57%.The Kappa value was 0.415,indicating relative consistency between CanPatrol TM and CytoploRare.CONCLUSION CTC detection is valuable for distinguishing LC from controls,and particularly E&M-CTC detection warrants further study.

Tumor microenvironment reprogramming by nanomedicine to enhance the effect of tumor immunotherapy

With the rapid development of the fields of tumor biology and immunology, tumor immunotherapy has been used in clinical practice and has demonstrated significant therapeutic potential, particularly for treating tumors that do not respond to standard treatment options. Despite its advances, immunotherapy still has limitations, such as poor clinical response rates and differences in individual patient responses, largely because tumor tissues have strong immunosuppressive microenvironments. Many tumors have a tumor microenvironment (TME) that is characterized by hypoxia, low pH, and substantial numbers of immunosuppressive cells, and these are the main factors limiting the efficacy of antitumor immunotherapy. The TME is crucial to the occurrence, growth, and metastasis of tumors. Therefore, numerous studies have been devoted to improving the effects of immunotherapy by remodeling the TME. Effective regulation of the TME and reversal of immunosuppressive conditions are effective strategies for improving tumor immunotherapy. The use of multidrug combinations to improve the TME is an efficient way to enhance antitumor immune efficacy. However, the inability to effectively target drugs decreases therapeutic effects and causes toxic side effects. Nanodrug delivery carriers have the advantageous ability to enhance drug bioavailability and improve drug targeting. Importantly, they can also regulate the TME and deliver large or small therapeutic molecules to decrease the inhibitory effect of the TME on immune cells. Therefore, nanomedicine has great potential for reprogramming immunosuppressive microenvironments and represents a new immunotherapeutic strategy. Therefore, this article reviews strategies for improving the TME and summarizes research on synergistic nanomedicine approaches that enhance the efficacy of tumor immunotherapy.

New roles of tumor-derived exosomes in tumor microenvironment

Throughout tumorigenesis, the co-evolution of tumor cells and their surrounding microenvironment leads to the development of malignant phenotypes. Cellular communication within the tumor microenvironment(TME) plays a critical role in influencing various aspects of tumor progression, including invasion and metastasis. The release of exosomes, a type of extracellular vesicle, by most cell types in the body, is an essential mediator of intercellular communication. A growing body of research indicates that tumor-derived exosomes(TDEs) significantly expedite tumor progression through multiple mechanisms, inducing epithelial-mesenchymal transition and macrophage polarization, enhancing angiogenesis, and aiding in the immune evasion of tumor cells. Herein, we describe the formation and characteristics of the TME, and summarize the contents of TDEs and their diverse functions in modulating tumor development. Furthermore, we explore potential applications of TDEs in tumor diagnosis and treatment.

Establishment of eye tumor biobank to provide resources for exploring new biomarkers of various ocular tumors

In addition to the lens,tumors can oceur in almost all tissues of the eye.Lacking of effective biomarkers makes diagnosis of ocular tumors difficult.Biobanks are important resources for biomarker discovery and assay development.To support the validation of novel biomarkers and assays,we established a biobank to collect body fluids and tissue and associate data from subjects with ocular tumor diseases.A standard operating procedure of collection,transportation,processing and preservation of human samples according to the experience of biobanks domestic and foreign have been established.Associated data had been collected and statistical analysis of the existing data had been performed.Cooperation between the eye tumor biobank and the Department of Ophthalmology,Xiangya Hospital,Central South University has been established,and various samples can be obtained.Currently,708 samples are available from 78 subjects with 11 types of benign tumors and 12 types of malignant tumors,including hemangioma,schwannoma,retinoblastoma,lymphoma,basal cell carcinoma,melanoma,sarcomas,ect.

Bioinformatics Analysis Revealed Potential Tumor Suppressors (KLF4/CGN), Oncogenes (SHH/LIF) and Biomarkers of Asian Stomach Adenocarcinoma

Stomach adenocarcinoma (STAD) is the fifth most prevalent cancer and the third leading cause of cancer-related death in the world and is more common in Asia than in most Western countries. There is an urgent need to identify potential novel oncogenes and tumor suppressor genes, and biomarkers for STAD. 6652 differentially expressed genes were identified between STAD and normal samples based on the transcriptome data analysis of the TCGA and GEO databases. 13 key modules were identified in STAD by WGCNA analysis. 293 potential STAD associated genes were identified from intersection by Venn Diagram. The 293 intersected genes were enriched in cell cortex and infection by GO and KEGG analysis. 10 hub genes were identified from PPI and Cytoscape analyses of the intersected genes. KLF4/CGN low and SHH/LIF high expression were associated with short overall survival of Asian STAD patients. Bioinformatics analysis revealed potential novel tumor suppressors (KLF4/CGN), oncogenes (SHH/LIF) and biomarkers for diagnosis, therapy and prognosis of STAD, specifically for Asian patients.

Validation of serum tumor biomarkers in predicting advanced cystic mucinous neoplasm of the pancreas

BACKGROUND Early detection of advanced cystic mucinous neoplasms[(A-cMNs),defined as high-grade dysplasia or malignancy]of the pancreas is of great significance.As a simple and feasible detection method,serum tumor markers(STMs)may be used to predict advanced intraductal papillary mucinous neoplasms(IPMNs)and mucinous cystic neoplasms(MCNs).However,there are few studies on the usefulness of STMs other than carbohydrate antigen(CA)19-9 for early detection of A-cMNs.AIM To study the ability of five STMs-CA19-9,carcinoembryonic antigen(CEA),CA125,CA724,and CA242 to predict A-cMNs and distinguish IPMNs and MCNs.METHODS We mainly measured the levels of each STM in patients pathologically diagnosed with cMNs.The mean levels of STMs and the number of A-cMN subjects with a higher STM level than the cutoff were compared respectively to identify the ability of STMs to predict A-cMNs and distinguish MCNs from IPMNs.A receiver operating characteristic curve with the area under curve(AUC)was also created to identify the performance of the five STMs.RESULTS A total of 187 patients with cMNs were identified and 72 of them showed AcMNs.We found that CA19-9 exhibited the highest sensitivity(SE)(54.2%)and accuracy(76.5%)and a moderate ability(AUC=0.766)to predict A-cMNs.In predicting high-grade dysplasia IPMNs,the SE of CA19-9 decreased to 38.5%.The ability of CEA,CA125,and CA724 to predict A-cMNs was low(AUC=0.651,0.583,and 0.618,respectively).The predictive ability of CA242 was not identified.The combination of STMs improved the SE to 62.5%.CA125 may be specific to the diagnosis of advanced MCNs.CONCLUSION CA19-9 has a moderate ability,and CEA,CA125,and CA724 have a low ability to predict A-cMNs.The combination of STM testing could improve SE in predicting A-cMNs.

Evaluation of 30 DNA damage response and 6 mismatch repair gene mutations as biomarkers for immunotherapy outcomes across multiple solid tumor types

Objective:DNA damage response(DDR)genes have low mutation rates,which may restrict their clinical applications in predicting the outcomes of immune checkpoint inhibitor(ICI)treatment.Thus,a systemic analysis of multiple DDR genes is needed to identify potential biomarkers of ICI efficacy.Methods:A total of 39,631 patients with mutation data were selected from the cBioPortal database.A total of 155 patients with mutation data were obtained from the Fudan University Shanghai Cancer Center(FUSCC).A total of 1,660 patients from the MSK-IMPACT cohort who underwent ICI treatment were selected for survival analysis.A total of 249 patients who underwent ICI treatment from the Dana-Farber Cancer Institute(DFCI)cohort were obtained from a published dataset.The Cancer Genome Atlas(TCGA)level 3 RNA-Seq version 2 RSEM data for gastric cancer were downloaded from cBioPortal.Results:Six MMR and 30 DDR genes were included in this study.Six MMR and 20 DDR gene mutations were found to predict the therapeutic efficacy of ICI,and most of them predicted the therapeutic efficacy of ICI,in a manner dependent on TMB,except for 4 combined DDR gene mutations,which were associated with the therapeutic efficacy of ICI independently of the TMB.Single MMR/DDR genes showed low mutation rates;however,the mutation rate of all the MMR/DDR genes associated with the therapeutic efficacy of ICI was relatively high,reaching 10%–30%in several cancer types.Conclusions:Coanalysis of multiple MMR/DDR mutations aids in selecting patients who are potential candidates for immunotherapy.

Intestinal Microbiota:Potential Tumor Biomarkers

Intestinal microecology is closely related to human health and plays an important role in metabolism,digestion,absorption and immunity.Disorders of the intestinal microbiota may lead to abnormalities of the immune system,and may be involved in the development of malignancy.This review summarizes the evidence supporting the use of intestinal microorganisms as tumor markers.In addition,this paper also summarizes the current perspectives regarding the involvement of intestinal microecology in the pathogenesis of cancer,providing a reference for potential biomarkers that could be used for the clinical diagnosis and response to treatment of tumors.

Hepatocellular carcinoma: Review of disease and tumor biomarkers

Hepatocellular carcinoma(HCC) is a common malignancy and now the second commonest global cause of cancer death. HCC tumorigenesis is relatively silent and patients experience late symptomatic presentation. As the option for curative treatments is limited to early stage cancers, diagnosis in non-symptomatic individuals is crucial. International guidelines advise regular surveillance of high-risk populations but the current tools lack sufficient sensitivity for early stage tumors on the background of a cirrhotic nodular liver. A number of novel biomarkers have now been suggested in the literature, which may reinforce the current surveillance methods. In addition, recent metabonomic and proteomic discoveries have established specific metabolite expressions in HCC, according to Warburg's phenomenon of altered energy metabolism. With clinical validation, a simple and non-invasive test from the serum or urine may be performed to diagnose HCC, particularly benefiting low resource regions where the burden of HCC is highest.