Predictive value of tumor markers in patients with recurrent hepatocellular carcinoma in different vascular invasion pattern

BACKGROUND： Four tumor markers for hepatocellular carcinoma（HCC）, alpha-fetoprotein（AFP）, glypican-3（GPC3）, vascular endothelial growth factor（VEGF） and des-gammacarboxy prothrombin（DCP）, are closely associated with tumor invasion and patient＇s survival. This study estimated the predictability of preoperative tumor marker levels along with pathological parameters on HCC recurrence after hepatectomy.METHODS： A total of 140 patients with HCC who underwent hepatectomy between January 2012 and August 2012 were enrolled. The demographics, clinical and follow-up data were collected and analyzed. The patients were divided into two groups： patients with macroscopic vascular invasion（Ma VI ＋） and those without Ma VI（Ma VI-）. The predictive value of tumor markers and clinical parameters were evaluated by univariate and multivariate analysis.RESULTS： In all patients, tumor size（〉8 cm） and Ma VI were closely related to HCC recurrence after hepatectomy. For Ma VI＋ patients, VEGF（〉900 pg/m L） was a significant predictor for recurrence（RR=2.421; 95% CI： 1.272-4.606; P=0.007）. The 1- and 2-year tumor-free survival rates for Ma VI＋ patients with VEGF ≤900 pg/m L versus for those with VEGF 〉900 pg/m L were 51.5% and 17.6% versus 19.0% and 4.8%（P〈0.001）. For Ma VI- patients, DCP 〉445 m Au/m L and tumor size 〉8 cm were two independent risk factors for tumor recurrence（RR=2.307, 95% CI： 1.132-4.703, P=0.021; RR=3.150, 95% CI： 1.392-7.127, P=0.006; respectively）. The 1- and 2-year tumor-free survival rates for the patients with DCP ≤445 m Au/m L and those with DCP 〉445 m Au/m L were 90.4% and 70.7% versus 73.2% and 50.5% respectively（P=0.048）. The 1-and 2-year tumor-free survival rates for the patients with tumor size ≤8 cm and 〉8 cm were 83.2% and 62.1% versus 50.0% and 30.0%, respectively（P=0.003）.CONCLUSIONS： The Ma VI＋ patients with VEGF ≤900 pg/m L had a relatively high tumor-free survival than those with VEGF 〉900 pg/m L. In the Ma VI- patients, DCP 〉445 m Au/m L and tumor size 〉8 cm were predictive factors for postoperative recurrence.

Early markers of reperfusion injury after liver transplantation: association with primary dysfunction

BACKGROUND： In patients with end-stage fiver disease, fiver transplantation is the only available curative treatment. Al- though the outcome and quality of life in the patients have improved over the past decades, primary dys- or nonfimction （PDF/PNF） can occur. Early detection of PDF and PNF is crucial and could lead to individual therapies. This study was designed to identify early markers of reperfusion injury and PDF in liver biopsies taken during the first hour after reperfusion.

Investigating Torsin‐1A‐interacting protein 1 as a predictive and immunological biomarker in cancer

Background:Cancer poses a significant global challenge,and with the pro-jected rise in cancer incidence,there is an urgent need to discover new targets and treatments to improve patient outcomes.Recent advancements in geno-mics technologies have enhanced our understanding of cancer's complexities and led to the emergence of pan‐cancer analysis as a valuable approach for identifying tumor targets.Torsin‐1A‐interacting protein 1(TOR1AIP1)is a membrane protein involved in various cellular processes.Emerging evidence suggests its potential involvement in cancer.Methods:In this study,we conducted a comprehensive analysis of multiple databases to explore TOR1AIP1 expression across different cancer types and stages.We also investigated its correlation with clinical outcomes,such as survival rates and drug sensitivity.Results:The results of our analysis showed significant deregulation of TOR1AIP1 expression in multiple cancer types and its association with clinical outcomes,with a particular emphasis on kidney renal clear cell carcinoma.The results of our study highlight the potential predictive value of TOR1AIP1 in cancer prognosis and therapy.Conclusions:This study establishes a solid foundation and rationale for future experimental investigations,which will contribute to a deeper under-standing of the significance of TOR1AIP1 in different cancer types,specifically in kidney renal clear cell carcinoma.

Multi-omics analysis of attenuated variant reveals potential evaluation marker of host damaging for SARS-CoV-2 variants

SARS-CoV-2 continues to threaten human society by generating novel variants via mutation and recombination.The high number of mutations that appeared in emerging variants not only enhanced their immune-escaping ability but also made it difficult to predict the pathogenicity and virulence based on viral nucleotide sequences.Molecular markers for evaluating the pathogenicity of new variants are therefore needed.By comparing host responses to wild-type and variants with attenuated pathogenicity at proteome and metabolome levels,six key molecules on the polyamine biosynthesis pathway including putrescine,SAM,dc-SAM,ODC1,SAMS,and SAMDC were found to be differentially upregulated and associated with pathogenicity of variants.To validate our discovery,human airway organoids were subsequently used which recapitulates SARS-CoV-2 replication in the airway epithelial cells of COVID-19 patients.Using ODC1 as a proof-ofconcept,differential activation of polyamine biosynthesis was found to be modulated by the renin-angiotensin system(RAS)and positively associated with ACE2 activity.Further experiments demonstrated that ODC1 expression could be differentially activated upon a panel of SARS-CoV-2 variants of concern(VOCs)and was found to be correlated with each VOCs’pathogenic properties.Particularly,the presented study revealed the discriminative ability of key molecules on polyamine biosynthesis as a predictive marker for virulence evaluation and assessment of SARS-CoV-2 variants in cell or organoid models.Our work,therefore,presented a practical strategy that could be potentially applied as an evaluation tool for the pathogenicity of current and emerging SARS-CoV-2 variants.

Prediction of disease course in inflammatory bowel diseases

Clinical presentation at diagnosis and disease course of both Crohn's disease(CD) and ulcerative colitis are heterogeneous and variable over time.Since most patients have a relapsing course and most CD patients develop complications(e.g.stricture and/or perforation),much emphasis has been placed in the recent years on the determination of important predictive factors.The identification of these factors may eventually lead to a more personalized,tailored therapy.In this TOPIC HIGHLIGHT series,we provide an update on the available literature regarding important clinical,endoscopic,fecal,serological/routine laboratory and genetic factors.Our aim is to assist clinicians in the everyday practical decisionmaking when choosing the treatment strategy for their patients suffering from inflammatory bowel diseases.

Is the disease course predictable in inflammatory bowel diseases?

During the course of the disease,most patients with Crohn's disease(CD) may eventually develop a stricturing or a perforating complication,and a significant number of patients with both CD and ulcerative colitis will undergo surgery.In recent years,research has focused on the determination of factors important in the prediction of disease course in inflammatory bowel diseases to improve stratification of patients,identify individual patient profiles,including clinical,laboratory and molecular markers,which hopefully will allow physicians to choose the most appropriate management in terms of therapy and intensity of follow-up.This review summarizes the available evidence on clinical,endoscopic variables and biomarkers in the prediction of short and long-term outcome in patients with inflammatory bowel diseases.

Investigation on Factors Associated with Severe Hand, Foot and Mouth Disease

Objective To analyze the clinical and laboratory features of patients with mild and severe HFMD to identify early predictive or diagnostic markers for severe cases. Methods Samples of feces, nasopharyngeal-swab specimens, peripheral blood, serum and cerebral spinal fluid were collected. Postmortem pathological examination was conducted on 2 dead patients with complication due to neurogenic pulmonary edema. Reverse transcription-polymerase chain-reaction(RT-PCR), culture and isolation of enterovirus 71(EV71) were performed to detect EV71 infection. Both univariate and multivariate logistic analysis were used to identify factors associated with severe cases. Results EV71 was mainly responsible for HFMD. In this study, 5 isolated EV71 strains belonged to C4 gene subtype. Compared with mild patients, EV71-RNA detection rate was higher and Cox A16 detection rate was lower among severe patients(P < 0.01). Inflammatory cell infiltration in the lung, cardiac and liver tissues were mild by postmortem pathological examination. It was found that body temperature, vomitting, limb tremor, neutrophil, blood glucose and EV71 infection were significantly related to the severe cases by univariate logistic analysis. However, after multivariate logistic regression analysis, only vomiting(OR 16.1, CI 2.3-110.5, P < 0.01) and limb tremor(OR 117.6, CI 13.8-1004.5, P < 0.01) were significantly and independently correlated with the severe cases.Conclusions EV71 was mainly responsible for HFMD, particularly for severe cases. Vomiting and limb tremor were predictive markers for severe cases.

DNA-repair ERCC1 Gene Polymorphisms in Epithelial Ovarian Cancer and Relation to Platinum Resistance and Survival

Objectives: Excision repair cross-complementation group 1 (ERCC1) is a key DNA repair gene in the nucleotide excision repair pathway which is activated in the repair of intra- and interstrand DNA crosslink caused by platinum-based treatment. Two single nucleotide polymorphisms (SNPs) of the ERCC1 gene, codon 118 C/T and C8092A, have been reported to be functional, but the influence on platinum resistance and survival is not yet clear. The primary aim of the present study was to investigate whether the two SNPs were associated with resistance to standard combination carboplatin and paclitaxel chemotherapy and the potential prognostic impact in newly diagnosed ovarian cancer patients. Methods: Serum samples from 202 patients with newly diagnosed ovarian cancer were assessed for ERCC1 SNP genotyping using real time PCR. All patients were treated with first line carboplatin/paclitaxel chemotherapy. Results: There were no correlation between the ERCC1 118 C/T and C8092A genotypes and platinum resistance (P = 0.79 and P = 0.36, respectively). Furthermore, the results showed no association to progression free survival (P = 0.18 and P = 0.16, respectively) or overall survival (P = 0.89 and P = 0.78, respectively) for the two SNPs. Conclusions: The ERCC1 118 C/T and C8092A polymorphisms did not have significant influence on clinical outcome defined as platinum resistance, PFS and OS.

Comparison of gemcitabine plus nab-paclitaxel and FOLFIRINOX in metastatic pancreatic cancer

BACKGROUND Gemcitabine plus nab-paclitaxel(GA)and modified FOLFIRINOX(FFX)have been widely used as standard first-line treatment in pancreatic cancer.However,it is unclear which regimen is more efficacious.AIM To evaluate a retrospective analysis comparing the efficacy and safety of FFX and GA as first-line chemotherapeutic regimens in patients with metastatic pancreatic cancer.METHODS We retrospectively analyzed and compared outcomes in 101 patients who presented with pancreatic cancer and were treated with either GA(n=54)or FFX(n=47).Moreover,we performed subgroup analysis based on the neutrophil/lymphocyte ratio(NLR)and Eastern Cooperative Oncology Group(ECOG)performance status.RESULTS There were no significant differences between two groups in baseline characteristics,except for the ECOG performance status.The median progression-free survival(PFS)(6.43 mo vs 4.90 mo,P=0.058)was comparable between two groups;however,median overall survival(OS)(10.17 mo vs 6.93 mo,P=0.008)was longer in patients who received GA regimen.In patients with ECOG 0(PFS:8.93 mo vs 5.43 mo,P=0.002;OS:16.10 mo vs 6.97 mo,P=0.000)and those with NLR<3(PFS:8.10 mo vs 6.57 mo,P=0.008;OS:12.87 mo vs 9.93 mo,P=0.002),GA regimen showed higher efficacy.CONCLUSION GA regimen may be recommended to the patients with NLR<3 or ECOG 0 status although GA and FFX showed comparable efficacy outcomes in patients with metastatic pancreatic cancer.

Role of hormone receptors and HER2 as prospective molecular markers for breast cancer:An update

This review provides an updated account on the current methods,principles and mechanism of action of therapies for the detection of molecular markers of therapeutic importance in the prognosis of breast cancer progression and recurrence,which includes estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor receptor2(HER2).Indeed,hormone-receptors namely,ER,PR,proto-oncogene HER2 are the basic molecular markers that are recognized and established prognostic factors and predictors of response,for therapeutic practice.These markers can be detected by using immunohistochemistry(IHC)and fluorescence in situ hybridization(FISH),which are established,faster and cost effective detection methods.These molecular markers along with clinicopathological prognostic parameters give the best prediction of the prognosis of cancer recurrence and progress.Finally,hormone receptors and HER2 as molecular markers are of prime therapeutic importance and have the capability to take part in future drug development techniques.

Intratumoral CD103^(+)CD8^(+)T cells predict response to neoadjuvant chemoimmunotherapy in advanced head and neck squamous cell carcinoma

Background Immune cell heterogenicity is known to determine the therapeutic response to cancer progression.Neoadjuvant chemoimmunotherapy(NACI)has shown clinical benefits in some patients with advanced head and neck squamous cell carcinoma(HNSCC),but the underlying mechanism behind this clinical response is unknown.The efficacy of NACI needs to be potentiated by identifying accurate biomarkers to predict clinical responses.Here,we attempted to identify molecules predicting NACI response in advanced HNSCC.Methods We performed combined single-cell RNA sequencing(scRNA-seq)and multiplex immunofluorescence(mIHC)staining with tumor samples derived from NACI-treated HNSCC patients to identify a new tumor-infiltrating cell(TIL)subtype,CD103^(+)CD8^(+)TILs,associated with clinical response,while both in vitro and in vivo assays were carried out to determine its antitumor efficiency.The regulatory mechanism of the CD103^(+)CD8^(+)TILs population was examined by performing cell-cell interaction analysis of the scRNA-seq data and spatial analysis of the mIHC images.Results We established intratumoral CD103^(+)CD8^(+)TILs density as a determinant of NACI efficacy in cancers.Our scRNA-seq results indicated that the population of CD103^(+)CD8^(+)TILs was dramatically increased in the responders of NACI-treated HNSCC patients,while mIHC analysis confirmed the correlation between intratumoral CD103^(+)CD8^(+)TILs density and NACI efficacy in HNSCC patients.Further receiver operating characteristic curve analysis defined this TIL subset as a potent marker to predict patient response to NACI.Functional assays showed that CD103^(+)CD8^(+)TILs were tumor-reactive T cells,while programmed cell death protein-1(PD-1)blockade enhanced CD103^(+)CD8^(+)TILs cytotoxicity against tumor growth in vivo.Mechanistically,targeting the triggering receptor expressed on myeloid cells 2-positive(TREM2^(+))macrophages might enhance the population of CD103^(+)CD8^(+)TILs and facilitate antitumor immunity during NACI treatment.Conclusions Our study highlights the impact of intratumoral CD103^(+)CD8^(+)TILs density on NACI efficacy in different cancers,while the efforts to elevate its population warrant further clinical investigation.