Predictive Prognostic Marker Research Articles

Identification of serum phosphatidylinositol glycan anchor biosynthesis class U protein as diagnostic biomarker for breast cancer.

Finding markers of breast cancer that are strong specificity and high. Sensitivity is important. The expression of phosphatidylinositol U（PIGU） protein is increased in a variety of tumor cells, but the role of its secreted fragment in breast cancer is lacking. Differential expression analysis was performed in breast cancer patients by bioinformatics method. Univariate survival analysis and ROC curve plotting were used to explore the correlation between serum PIGU and the prognosis of breast cancer patients. ELISA was used to detect serum PIGU level. Electrochemiluminescence immunoassay was used to determine serum carcinoembryonic antigen (CEA), carbohydrate antigen-153(CA153) and carbohydrate antigen-125 (CA125) levels. The expression level of PIGU protein in breast cancer tumor tissues was higher than that in normal tissues, and PIGU expression level was a prognostic risk factor for breast cancer patients (HR > 1, p < 0.05) and had good predictive power (AUC = 0.8941). Compared with healthy individuals, the serum PIGU level of breast cancer patients was significantly highly expressed (p < 0.01), and the serum PIGU expression level was weakly positively correlated with CEA (r = 0.3270), but not significantly correlated with CA153 and CA125 (p > 0.05). PIGU has the potential to be a predictive prognostic marker for breast cancer.

Is switching to T-DM1 still justified in HER2-negative residual breast cancer after neoadjuvant systemic therapy?

The standard of care for HER2-positive and hormone receptor-positive breast cancer patients who receive neoadjuvant chemotherapy (NACT) combined with trastuzumab, with or without pertuzumab, is to continue with adjuvant T-DM1 in cases of an incomplete response according to KATHERINE trial results. However, the optimal management for patients with residual disease with loss of HER2 expression is not widely studied. Loss of HER2 expression after NACT with anti HER2 is a rarer event with questionable value both as a predictive prognostic marker.

Predicting survival in patients with SARS-CoV-2 based on cytokines and soluble immune checkpoint regulators.

Coronavirus disease 2019 (COVID-19) has been widespread for over four years and has progressed to an endemic stage. Accordingly, the evaluation of host immunity in infected patients and the development of markers for prognostic prediction in the early stages have been emphasized. Soluble immune checkpoints (sICs), which regulate T cell activity, have been reported as promising biomarkers of viral infections. In this study, quantitative values of 17 sICs and 16 cytokines (CKs) were measured using the Luminex multiplex assay. A total of 148 serum samples from 100 patients with COVID-19 were collected and the levels were compared between survivors vs. non-survivors and pneumonic vs. non-pneumonic conditions groups. The impact of these markers on overall survival were analyzed using a machine learning algorithm. sICs, including sCD27, sCD40, herpes virus entry mediator (sHVEM), T-cell immunoglobulin and mucin-domain containing-3 (sTIM-3), and Toll-like receptor 2 (sTLR-2) and CKs, including chemokine CC motif ligand 2 (CCL2), interleukin-6 (IL-6), IL-8, IL-10, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF- α), were statistically significantly increased in the non-survivors compared to those of in the survivors. IL-6 showed the highest area under the receiver-operating curve (0.844, 95% CI = 0.751-0.913) to discriminate non-survival, with a sensitivity of 78.9% and specificity of 82.4%. In Kaplan-Meier analysis, patients with procalcitonin over 0.25 ng/mL, C-reactive protein (CRP) over 41.0 mg/dL, neutrophil-to-lymphocyte ratio over 18.97, sCD27 over 3828.8 pg/mL, sCD40 over 1283.6 pg/mL, and IL-6 over 21.6 pg/mL showed poor survival (log-rank test). In the decision tree analysis, IL-6, sTIM-3, and sCD40 levels had a strong impact on survival. Moreover, IL-6, CD40, and CRP levels were important to predict the probability of 90-d mortality using the SHapley Additive exPlanations method. sICs and CKs, especially IL-6, sCD27, sCD40, and sTIM-3 are expected to be useful in predicting patient outcomes when used in combination with existing markers.

Adverse Reactions to the Orphan Drug Cerliponase Alfa in the Treatment of Neurolipofuscinosis Type 2 (CLN2).

Background/Objectives: Neuronal Ceroid Lipofuscinosis type 2 is a rare pathology affecting mainly the central nervous system (CNS) and retina, and is caused by variants in the gene encoding the lysosomal enzyme tripeptidyl peptidase 1. Therapy with enzyme replacement through the brain infusion of the orphan drug cerliponase alfa, a recombinant human tripeptidyl peptidase 1 enzyme replacement therapy delivered via intracerebroventricular infusion, has been approved for Neuronal Ceroid Lipofuscinosis type 2 disease. The safety profile of cerliponase alfa has been established based on pre-authorization studies; currently, no post-marketing investigation has been performed to confirm it. Here, a descriptive analysis of real-world spontaneous reporting data of suspected adverse reactions (SARs) to cerliponase alfa in the EudraVigilance database was performed to compile clear information on the safety profile. Methods: Suspected adverse reactions to cerliponase alfa reported in the data system EudraVigilance were analyzed for age, sex of the patient, adverse reactions, and the indication for use. Results: Cases with suspected adverse reactions to cerliponase alfa were found to be more frequent in female patients (58.1%) and in children aged 3-11 years. The most common adverse reactions were, in decreasing order, fever/pyrexia, device-related infection, vomiting, seizures/convulsions, pleocytosis, irritability, ventriculitis, and respiratory disorders. Conclusions: The results confirm the safety profile of cerliponase alfa established with pre-registration clinical studies but suggest the need for further studies to investigate the occurrence of adverse reactions, as possible predictive prognostic markers, in more depth.

Evaluation of proprotein convertase subtilsin /kexin 9(PCSK9) in serum of men hypertensive patients

High blood pressure is considered a major factor for the development of heart disease and vascular disease in elderly people, due to higher tension in arteries leading to hypertension. PCSK9 is a proprotein convertase that increases circulating LDL levels by directing hepatic LDL receptors into lysosomes for degradation. The effects of PCSK9 on hepatic LDL receptors and contribution to atherosclerosis via the induction of hyperlipidemia are well defined. Methods: The case-control study included (90) subjects divided into sixty (60) male patients. Samples were collected for patients with high blood pressure in Al-Sadr Medical City in Najaf Al-Ashraf / Iraq, and laboratory tests were conducted to measure the lipid profile in Al-Sadr Medical City laboratories. Height and weight were measured, and other information was also collected. The ELISA test was performed in the advanced animal laboratory in the college’s Department of Biology. Department of Science/University of Kufa. The study was conducted by collecting samples and measuring all factors in the period from 1/11/2023 to 2/2/2024. A control group study of 30 men was also conducted. All groups that appeared healthy were matched in age, and patients with diabetes, kidney disease and heart disease were excluded from the study, as well as any other systemic diseases. Conclusion: The present study concluded that PCSK9considered as a prognostic marker for prediction of hypertension. Also, PCSK9 was very related in hypertensive patients with hyperlipidemia (cholesterol, TG, LDL, &amp; HDL). High biomarker level associated with ages especially at new diagnosis without treatment and with short duration of disease. Smoking plays important roles with high a level of PCSK9 in hypertensive patients. The genetic may play a role in present study by high level of This biomarker in familial hypertensive patients. Obesity has a crucial role in in hypertensive patients with high PCSK9 level.

Current progress and prospects for G protein-coupled estrogen receptor in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a biologically and clinically heterogeneous disease. The G protein-coupled estrogen receptor (GPER) plays a crucial role in mediating the effect of estrogen and estrogen-like compounds in TNBC cells. Compared with other subtypes, GPER has a higher expression in TNBC. The GPER mechanisms have been thoroughly characterized and analyzed in estrogen receptor α (ERα) positive breast cancer, but not in TNBC. Our previous work revealed that a higher expression of GPER mRNA indicates a better prognosis for ERα-positive breast cancer; however, its effects in TNBC differ. Whether GPER could serve as a predictive prognostic marker or therapeutic target for TNBC remains unclear. In this review, we provide a detailed introduction to the subcellular localization of GPER, the different effects of various ligands, and the interactions between GPER and closely associated factors in TNBC. We focused on the internal molecular mechanisms specific to TNBC and thoroughly explored the role of GPER in promoting tumor development. We also discussed the interaction of GPER with specific cytokines and chemokines, and the relationship between GPER and immune evasion. Additionally, we discussed the feasibility of using GPER as a therapeutic target in the context of existing studies. This comprehensive review highlights the effects of GPER on TNBC, providing a framework and directions for future research.

Platelet-to-lymphocyte ratio as a prognostic predictive marker on adults with traumatic brain injury: Systematic review.

The platelet-to-lymphocyte ratio (PLR) has emerged as a prognostic predictive marker in various diseases, but its role in traumatic brain injury (TBI) has not been fully elucidated. This study aims to evaluate the role of PLR as a prognostic predictive marker in adults with TBI. This systematic review was conducted according to the Preferred Reporting Items in the Systematic Review and Meta-analysis Guidelines 2020. A comprehensive search was performed using PubMed, Google Scholar, Scopus, Crossref, OpenAlex, Semantic Scholar, Library of Congress, and Jisc Library Hub Discover database to identify relevant studies published up to February 2023. Both prospective and retrospective observational studies written in English or Indonesian were included in the study. No restrictions were placed on the year and country of publication and duration of follow-up. Study quality was evaluated using the Newcastle-Ottawa Scale (NOS), and the risk of bias was estimated using the Cochrane Risk of Bias Assessment Tool for Nonrandomized Research (Ro-BANS) tool. A narrative synthesis was also conducted to summarize the findings. We retrieved 1644 references using the search strategy, and 1623 references were excluded based on screening the title and abstract. The full text was retrieved for 20 articles and subjected to the eligibility criteria, of which 16 were excluded from the study. Four papers with a total of 1.467 sample sizes were included in the review. The median of NOS for study quality was 8-9, with the risk of selection bias using the Ro-BANS tool being low in all studies except for the blinding outcome assessments, which are all unclear. The study finding suggests that the PLR has the potential as an independent prognostic predictive marker in adult patients with TBI. In three studies, a high level of admission PLR may independently predict an increasing mortality risk in 30 days and adverse outcomes measured by the Glasgow outcome scale in 6 months following TBI. However, one study shows that PLR may have limited value as a predictor of mortality or favorable neurological outcomes compared to other hematological parameters. Further studies were needed to establish the clinical utility of PLR and fill the present gaps. This systematic review provides evidence supporting the utilization of PLR as a prognostic predictive marker in adult patients with TBI. The PLR can mainly be utilized, especially in rural practice, as PLR is a simple, low-cost, and routinely performed hematological examination.

Study of expression of GLUT-1 in oral potentially malignant disorders and oral squamous cell carcinoma: An immuno-histochemical analysis.

Glucose is the chief source of energy for cells, and glucose transporter 1 (GLUT-1) is one of the most common glucose transporters in humans. Tumour cells are known to express hypoxia-related protein, and these may allow tumour cells to survive under a sustained hypoxic environment. Surviving cells develop a more aggressive phenotype, which results in poor prognosis. Expression and comparison of GLUT-1 in normal tissues, potentially malignant disorders (PMDs), and oral squamous cell carcinoma (OSCC) and comparison of expression in different grades of OSCC. A total of 57 cases (10 normal, 17 PMD, and 30 cases of OSCC) were stained immuno-histochemically with GLUT-1. The expression was scored as 0, 1, 2, 3, and 4 for negative, mild, moderate, severe, and intense staining, respectively. GLUT-1 expression was detected in all grades of OSCC. A significant correlation was found on comparing normal and OSCC, normal and PMDs, and PMD and OSCC. The expression of GLUT-1 was significant when compared with different histopathological grades of OSCC. Expression of GLUT-1 increased from normal to PMDs to increasing grades of OSCC and hence can be used as a prognostic predictive marker for OSCC.

Higher Mixed lineage Kinase Domain-like protein (MLKL) is associated with worst overall survival in adult-type diffuse glioma patients.

Recently, the search for novel molecular markers in adult-type diffuse gliomas has grown substantially, yet with few novel breakthroughs. As the presence of a necrotic center is a differential diagnosis for more aggressive entities, we hypothesized that genes involved in necroptosis may play a role in tumor progression. Given that MLKL is the executioner of the necroptotic pathway, we evaluated whether this gene would help to predict prognosis of adult gliomas patients. We analyzed a publicly available retrospective cohort (n = 530) with Kaplan Meier survival analysis (p<0.0001) and both uni- and multivariate Cox regression models. We determined that MLKL is an independent predictive prognostic marker for overall survival in these patients (HR: 2.56, p<0.001), even when controlled by the CNS5 gold-standard markers, namely IDH mutation and 1p/19q Codeletion (HR: 1.68, p = 0.013). These findings were confirmed in a validation cohort (n = 325), using the same cutoff value. Interestingly, higher expression of MLKL is associated with worse clinical outcome for adult-type diffuse glioma patients, which is opposite to what was found in other cell cancer types, suggesting that necroptosis undertakes an atypical detrimental role in glioma progression.

Identification of a potential prognostic plasma biomarker of acute ischemic stroke via untargeted LC-MS metabolomics.

Strokeisthesuddendeathofbraincellsinalocalized areaduetoan inadequatebloodflow or blood vessel rupture, and it seriously affects the quality of life. The metabolite biomarkers are needed for predicting the functional outcome of acute ischemic stroke (AIS). To identify biomarkers for AIS, untargeted LC/MS metabolomics was performed on plasma samples from subjects with favorable prognosis (mRS ≤ 2) and unfavorable prognosis (mRS>2). The identified markers were further absolutely quantified by a targeted MRM approach. There were 10 upregulated and 26 downregulated markers. Among these candidates, one was successfully identified as glycocholic acid and then absolutely quantified in plasma samples. Glycocholic acid could discriminate between subjects with favorable and unfavorable prognosis with an area under the curve (AUC) of 0.68 and odds ratio of 5.88. Glycocholic acid was identified as a potential plasma metabolite marker of non-progressive outcomes after ischemic stroke and could serve as predictive prognostic markers for clinical acute stroke outcomes.

Proteomic profiling and functional characterization of serum-derived extracellular vesicles in the mucinous and non-mucinous colon adenocarcinoma.

Mucinous adenocarcinoma (MC) is a distinct pathological subtype of colon adenocarcinoma, which is associated with a worse prognosis compared with non-mucinous adenocarcinoma (AC). However, clear distinctions between MC and AC remain unknown. Extracellular vesicles (EVs) are a class of enclosed vesicles containing proteins, lipids, and nucleic acids that are secreted by cells into surrounding tissues or into serum. The EVs could facilitate tumorigenesis by regulating tumor cell proliferation, invasiveness, metastasis, angiogenesis, and evasion of immune surveillance. Quantitative proteomics analysis was performed to determine the characterization and biological differences of serum-derived EVs in two subtypes of colon adenocarcinoma (MC and AC). Serum-derived EVs from patients with MC, AC, and healthy volunteers were included in this study. The role of PLA2G2A in cell migration and invasion were evaluate with transwell assay, and its prognostic predictive value was further assessed based on TCGA database. Quantitative proteomics analysis revealed 846 differentially expressed proteins (DEPs) in EVs from MC patients compared with those from AC patients. Bioinformatics analysis revealed that the most prominent protein cluster included those involved in cell migration and the tumor microenvironment. Overexpression of PLA2G2A, one of the key EV proteins upregulated in patients with MC, in colon cancer cell line SW480 promoted the cell invasion and migration ability. In addition, the high level of PLA2G2A is associated with poor prognosis of colon cancer patients harboring BRAF mutations. Further, after EV stimulation, proteomic analysis of recipient SW480 cells showed that MC-derived EVs activated multiple cancer-related pathways, including the Wnt/β-Catenin signaling pathway, and might promote the malignancy of mucinous adenocarcinoma through these pathways. The identification of differential protein profiles between MC and AC helps to elucidate the underlying molecular mechanisms of MC pathogenesis. The PLA2G2A in EVs is a potential prognostic predictive marker for those patients harboring with BRAF mutations.

CDX-2 expression correlates with clinical outcomes in MSI-H metastatic colorectal cancer patients receiving immune checkpoint inhibitors

Immune checkpoint inhibitors (ICIs) showed efficacy in metastatic colorectal cancer (mCRC) with mismatch-repair deficiency or high microsatellite instability (dMMR-MSI-H). Unfortunately, a patient’s subgroup did not benefit from immunotherapy. Caudal-related homeobox transcription factor 2 (CDX-2) would seem to influence immunotherapy’s sensitivity, promoting the chemokine (C-X-C motif) ligand 14 (CXCL14) expression. Therefore, we investigated CDX-2 role as a prognostic-predictive marker in patients with mCRC MSI-H. We retrospectively collected data from 14 MSI-H mCRC patients treated with ICIs between 2019 and 2021. The primary endpoint was the 12-month progression-free-survival (PFS) rate. The secondary endpoints were overall survival (OS), PFS, objective response rate (ORR), and disease control rate (DCR). The PFS rate at 12 months was 81% in CDX-2 positive patients vs 0% in CDX-2 negative patients (p = 0.0011). The median PFS was not reached (NR) in the CDX-2 positive group versus 2.07 months (95%CI 2.07–10.8) in CDX-2 negative patients (p = 0.0011). Median OS was NR in CDX-2-positive patients versus 2.17 months (95% Confidence Interval [CI] 2.17–18.7) in CDX2-negative patients (p = 0.026). All CDX-2-positive patients achieved a disease response, one of them a complete response. Among CDX-2-negative patients, one achieved stable disease, while the other progressed rapidly (ORR: 100% vs 0%, p = 0.0005; DCR: 100% vs 50%, p = 0.02). Twelve patients received 1st-line pembrolizumab (11 CDX-2 positive and 1 CDX-2 negative) not reaching median PFS, while two patients (1 CDX-2 positive and 1 CDX-2 negative) received 3rd-line pembrolizumab reaching a median PFS of 10.8 months (95% CI, 10.8–12.1; p = 0.036). Although our study reports results on a small population, the prognostic role of CDX-2 in CRC seems confirmed and could drive a promising predictive role in defining the population more sensitive to immunotherapy treatment. Modulating the CDX-2/CXCL14 axis in CDX-2-negative patients could help overcome primary resistance to immunotherapy.

Preoperative CA19-9 and GGT ratio as a prognostic indicator in ampullary carcinoma

Background and aimsIn recent years, more and more inflammatory indicators have been studied to predict the long-term survival of patients with ampullary carcinoma (AC) after radical resection, but these prognostic indicators are still controversial. Therefore, based on previous inflammation scores, this study established a novel, easily accessible, more feasible and more predictive prognostic marker [Carbohydrate antigen199 to gamma-glutamyltransferase ratio (CA19-9/GGT)] to better assess the prognostic significance in AC patients undergoing radical resection.MethodsOverall survival (OS) and recurrence-free survival (RFS) were analyzed by Cox regression model. Correlation between CA19-9/GGT and clinicopathological variables were analyzed by Chi-squared test, Fisher ' s exact test, independent sample t test and Mann–Whitney U test. The performance of prognostic indexes is compared by the consistency index (C-index). The prediction accuracy of nomogram is further confirmed by calibration curve and decision curve analysis (DCA).ResultsCA19-9/GGT was an independent risk factor affecting OS [P = 0.001, hazard ratio (HR) 2.459, 95% confidence intervals (CI) 1.450–4.167] and RFS (P = 0.002, HR 2.333, 95% CI 1.371–3.971) in multivariate analysis. The optimal cut-off value of CA19-9/GGT was 0.14. In CA19-9/GGT correlation analysis, high risk group (> 0.14) was significantly associated with poor prognosis. The predictive performance of CA19-9/GGT (OS: C-index = 0.753, RFS: C-index = 0.745) was confirmed to be superior to other prognostic indicators according to the C-index. Compared with the simple AJCC staging system, the Nomogram prediction model (OS: C-index = 0.787, RFS: C-index = 0.795) established by the combination of CA19-9/GGT and AJCC 8th TNM staging system has higher prediction accuracy.ConclusionsCA19-9/GGT was an independent prognostic indicator after radical resection of AC. Incorporating CA19-9/GGT into the AJCC TNM staging system optimized the prediction accuracy of the TNM staging system, and further verified the predictive value of CA19-9/GGT.

Expression, tumor immune infiltration, and prognostic impact of HMGs in gastric cancer.

In the past decade, considerable research efforts on gastric cancer (GC) have been expended, however, little advancement has been made owing to the lack of effective biomarkers and treatment options. Herein, we aimed to examine the levels of expression, mutations, and clinical relevance of HMGs in GC to provide sufficient scientific evidence for clinical decision-making and risk management. GC samples were obtained from The Cancer Genome Atlas (TCGA). University of California Santa Cruz (UCSC) XENA, Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier Plotter, cBioPortal, GeneMANIA, STRING, LinkedOmics, and DAVID databases were employed. The "ggplot2" package in the R software (×64 3.6.3) was used to thoroughly analyze the effects of HMGs. qRT-PCR was performed to assess HMG levels in GC cell lines. A total of 375 GC tissues and 32 paraneoplastic tissues were analyzed. The levels of HMGA1, HMGA2, HMGB1, HMGB2, HMGB3, HMGN1, HMGN2, and HMGN4 expression were increased in GC tissues relative to normal gastric tissues. HMGA1, HMGA2, HMGB1, HMGB2, and HMGB3 were highly expressed in GC cell lines. The OS was significantly different in the group showing low expressions of HMGA1, HMGA2, HMGB1, HMGB2, HMGB3, HMGN2, HMGN3, and HMGN5. There was a significant difference in RFS between the groups with low HMGA2, HMGB3, and high HMGN2 expression. The levels of HMGA2, HMGB3, and HMGN1 had a higher accuracy for prediction to distinguish GC from normal tissues (AUC value > 0.9). HMGs were tightly associated with immune infiltration and tumor immune escape and antitumor immunity most likely participates in HMG-mediated oncogenesis in GC. GO and KEGG enrichment analyses showed that HMGs played a vital role in the cell cycle pathway. Our results strongly suggest a vital role of HMGs in GC. HMGA2 and HMGB3 could be potential markers for prognostic prediction and treatment targets for GC by interrupting the cell cycle pathway. Our findings might provide renewed perspectives for the selection of prognostic biomarkers among HMGs in GC and may contribute to the determination of the optimal strategy for the treatment of these patients.

Insights into the underlying choroid in different stages of idiopathic epiretinal membranes after Viteromacular surgery.

The purpose of the study was to longitudinally investigate the correlation between choroidal morphologic and vascular parameters and postoperative visual outcome in different stages of idiopathic epiretinal membranes (iERMs). A prospective, observational, institutional case series of 102 consecutive patients diagnosed with unilateral iERMs were recruited at Peking University Third Hospital and were followed up for 12 months after surgical treatment with vitrectomy. Participants were classified into four stages according to current staging scheme. All eligible subjects underwent standardized imaging evaluation of choroidal parameters including subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI), and choroidal capillary perfusion (CCP) at baseline and each follow-up by enhanced depth optical coherence tomography (EDI-OCT) and OCT angiography (OCTA). Longitudinal follow-up of choroidal parameters over 12 months was analysed, and their correlations with best-corrected visual acuity (BCVA) were also assessed for predictive prognostic value. CVI and CCP were significantly correlated with BCVA at each follow-up examination (all p < 0.05). However, SFCT exhibited no variation among different stages of iERMs at baseline (p=0.981) or during follow-up (p=0.520). The preoperative CVI correlated with 12-month postoperative BCVA (p < 0.001) and its predictive prognostic effect on BCVA was validated in multiple regression analysis (p=0.006). CVI varied among different stages of iERM and was significantly correlated with visual outcomes after the surgery. CVI could serve as a predictive prognostic marker in iERMs, which further indicates the underlying choroid should be taken into consideration in clinical evaluation of iERMs.

Increased expression of METTL3 in pancreatic cancer tissues associates with poor survival of the patients

BackgroundMethyltransferase-like 3 (METTL3) expression could be found in various normal and cancerous tissues. As of now, the clinical significance of METTL3 expression in human pancreatic cancer (PC) tissues still remains to be understood. Our present study aims to investigate the prognostic value and clinical implications of METTL3 expression in PC tissues.MethodsThe TCGA, GTEx, and GEO public databases were used to study the mRNA expression level of the m6A family members and its relationship among PC tissues and normal pancreatic tissue. The immunohistochemistry was used to analyze the difference of METTL3 expression between cancer tissues and adjacent normal tissues. The prognostic value was evaluated by using the Log-rank survival analysis and Cox model analysis. PAAD samples from TCGA and GEO databases were used to perform the immune infiltration analysis and gene set enrichment analysis based on the genes that were highly correlated with METTL3.ResultsBased on the analysis of TCGA, GTEx, and GEO public database, we found that the m6A family members showed a higher correlation in PC tissues compared to normal pancreatic tissues, and the mRNA expression level of the m6A family members showed a significant difference between PC tissues and adjacent normal tissues. Moreover, scRNA-seq data indicated that METTL3 showed a higher expression level in malignant epithelial cells. Our immunohistochemistry results also confirmed that the intensity of METTL3 immunostaining in PC tissues was significantly higher than that in adjacent normal tissues (P = 0.015). The overall survival (OS) of PC patients with high expression of METTL3 protein were significantly poorer than those with low expression of METTL3 protein (HR = 1.788, 95% CI 1.071–2.984, P = 0.026). Further analysis of PC data from the database showed that METTL3 expression was associated with a variety of tumor-infiltrating immune cells and was involved in m6A modification and metabolism in PC tissues.ConclusionIncreased METTL3 expression at the protein level could be found in PC tissues, suggesting that the METTL3 expression was involved in the progression of PC and could serve as an important marker for prognostic prediction of this malignancy.

TRKB acts as a prognostic predictive marker in Her-2 positive breast cancer

Human epidermal growth factor receptor 2 (Her-2) positive breast cancer (BC) was associated with an increased risk for brain metastases. Tropomyosin receptor kinase (TRKB) is a specific binding receptor for brain-derived neurotrophic factor associated with brain metastases. However, TRKB was still unknown to be involved in Her-2 positive BC. A tissue microarray comprised of 60 Her-2 positive BC cases and 32 matched adjacent normal samples was analyzed for TRKB expression by immunohistochemical staining. Results were compared to clinicopathologic and survival data by univariate and multivariate analysis. Furthermore, we explored the co-expression genes and related functional proteins using GEPIA, Kaplan-Meier plotter, LinkedOmics and PPI. We found that TRKB protein expression levels were elevated in Her-2 positive BC, and high levels of TRKB expression were associated with vascular invasion, more lymph nodes metastases and more advanced TNM stage as well as poorer OS. TRKB was confirmed as an independent prognostic factor for Her-2 positive BC by univariate and multivariate analysis. Besides, enrichment analyses revealed that protein kinase B signaling was highly correlated to TRKB in Her-2 positive BC. Therefore, TRKB may act as a potential prognostic target and biomarker for Her-2 positive BC.

CXCL1 might be a useful predictive prognostic marker in patients with gastric cancer

CXCL1 might be a useful predictive prognostic marker in patients with gastric cancer

Topoisomerase II α Gene as a Marker for Prognostic Prediction of Hepatocellular Carcinoma: A Bioinformatics Analysis

ObjectiveTo investigate the expression of topoisomerase II α (TOP2α) in hepatocellular carcinoma (HCC) and its role in predicting prognosis of HCC patients. MethodsWe used HCC-related datasets in UALCAN, HCCDB, and cBioPortal databases to analyze the expression and mutation of TOP2α and its co-expressed genes in HCC tissues. GO function and KEGG pathway enrichment of TOP2α and its co-expressed genes were identified. The TIMER database was used to analyze infiltration levels of immune cells in HCC. The impacts of TOP2α and its co-expression genes and the infiltrated immune cells on the survival of HCC patients were assayed by Kaplan-Meier plotter analysis. ResultsTOP2α and its co-expression genes were highly expressed in HCC (P < 0.001) and detrimental to overall survival of HCC patients (P < 0.001). TOP2α and its co-expression genes were mainly involved in cell mitosis and proliferation, and cell cycle pathway (ID: hsa04110, P = 0.00194S). TOP2α and its co-expression genes were mutated in HCC and the mutations were significantly detrimental to overall survival (P = 0.0247) and disease-free survival (P = 0.026S) of HCC patients. High TOP2α expression was positively correlated with the infiltration of B cell (r = 0.4S9, P < 0.01), CD8+T cell (r = 0.312, P < 0.01), CD4+T cell (r = 0.370, P < 0.01), macrophage (r = 0.459, P < 0.01), neutrophil (r = 0.405, P < 0.01), and dendritic cell (r = 0.473, P < 0.01) in HCC. The CD8+T cell infiltration significantly prolonged the 3- and 5-year survival of HCC patients (all P < 0.05), and CD4+T cell infiltration significantly shortened the 3-, 5-, and 10-year survival of HCC patients (all P < 0.05) ConclusionTOP2α may be an oncogene, which was associated with poor prognosis of HCC patients and could be used as a biomarker for the prognostic prediction of HCC.

PET-Uptake Reduction into Lymph Nodes After Neoadjuvant Therapy is Highly Predictive of Prognosis for Patients Who have Thoracic Esophageal Squamous Cell Carcinoma Treated with Chemoradiotherapy Plus Esophagectomy.

Patients with 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET)-positive lymph nodes before treatment have a poor prognosis after esophagectomy. This study investigated whether FDG uptake into lymph nodes on FDG-PET (PET-N) during the pre- or posttreatment stage is more predictive of survival for thoracic esophageal squamous cell carcinoma (TESCC) patients who received neoadjuvant chemoradiotherapy (NACRT) followed by esophagectomy. Of 129 TESCC patients with clinical lymphatic metastasis who underwent curative-intent esophagectomy after NACRT between 2010 and 2018, 97 who received PET before and after NACRT were enrolled in the study. The study defined lymph nodes with a maximum standardized uptake value (SUVmax) greater than 2.5 on FDG-PET before NACRT as cPET-N(+) and after NACRT as CRT-cPET-N(+). Both the cPET-N(+) and CRT-cPET-N(-) patients were defined as PET-N responders. Survival was analyzed using the Kaplan-Meier method and Cox proportional hazard models. No significant difference in survival was detected between the cPET-N(+) and cPET-N(-) patients. However, the CRT-cPET-N(-) patients had significantly better 5-year overall survival (OS) and disease-specific survival (DSS) than the CRT-cPET-N (+) patients. The PET-N responders had significantly better 5-year OS and DSS than the PET-N non-responders, and PET-N response was an independent prognostic factor for 5-year DSS. The PET-N response is a highly predictive prognostic marker for TESCC patients who undergo NACRT followed by esophagectomy. The PET-N response may help clinicians to establish a strategy for perioperative treatments that improves survival for patients with lymph node metastasis in TESCC.