Potential Prognostic Biomarker In Patients Research Articles

Knockdown of CENPF induces cell cycle arrest and inhibits epithelial‑mesenchymal transition progression in glioma.

Gliomas are among the most common malignant tumors of the central nervous system. Despite surgical resection followed by postoperative radiotherapy and chemotherapy, their prognosis remains unfavorable. The present study aimed to assess new mechanisms and explore promising prognostic biomarkers for patients with glioma using comprehensive bioinformatics analysis and in vitro and in vivo assays. Overlapping differentially expressed genes were screened from The Cancer Genome Atlas, GSE111260 and GSE16011 samples for protein-protein interaction networks, a risk score model, gene mutation analysis and a nomogram to identify the prognostic hub genes. Subsequently, an immunoassay was performed to determine key genes. Functional and animal assays were then performed to assess the tumorigenesis of the key genes in glioma. Using bioinformatics analysis, centromere protein F (CENPF), kinesin superfamily member 20A, kinesin superfamily protein 4A and marker of proliferation Ki-67 were identified as potential prognostic biomarkers for patients with glioma. Furthermore, CENPF knockdown was demonstrated to suppress the proliferation and metastasis of glioma cells, and induce G2 arrest in the cell cycle. Moreover, CENPF knockdown was revealed to decrease Vimentin and increase E-cadherin levels in glioma cells, and significantly reduce the size and mass of tumors in vivo. Overall, the present study identified new clinical biomarkers and revealed that CENPF may promote glioma progression by regulating the epithelial-mesenchymal transition pathway. By elucidating the complexities of glioma and identifying prognostic biomarkers, the present research enables further improvement of patient outcomes and the advancement of precision medicine for this disease.

Combined Bone Mineral Density (BMD) and Monocyte-to-Lymphocyte Ratio (MLR) Predicts Recurrence and Prognosis in Hepatocellular Carcinoma Patients Following Liver Resection.

Bone mineral density (BMD) and monocyte-to-lymphocyte ratio (MLR) were recently identified as novel risk factors for patients with several malignancies. The objective of this study was to validate the role of preoperative BMD/MLR as a potential prognostic biomarker in patients with hepatocellular carcinoma (HCC) undergoing liver resection. This investigation enrolled 442 adult patients diagnosed with HCC who underwent liver resection. The patients were classified into high- and low-BMD/MLR groups based on the median, and forward stepwise logistic regression was employed to identify independent predictors for early HCC recurrence. To mitigate the impact of confounding factors, a propensity score matching (PSM) analysis was conducted between patients in the high- and low-BMD/MLR groups. The Kaplan-Meier method was employed to assess and compare the disease-free survival (DFS) and overall survival (OS) between the two cohorts. The study categorized patients into high-BMD/MLR and low-BMD/MLR groups. Forward stepwise logistic regression analysis revealed that low BMD/MLR (P < 0.001), tumor size > 50 mm (P < 0.001), and AFP > 200 ug/L (P = 0.001) were significantly associated with the early recurrence of HCC. Moreover, the results suggested that DFS and OS were significantly shorter in the low-BMD/MLR group compared to the high-BMD/MLR group, both before and after PSM (P < 0.05). Preoperative BMD/MLR held promise as a prognostic biomarker for early recurrence and prognosis in patients with HCC who underwent liver resection. Furthermore, the integration of tumor size, AFP level, and BMD/MLR demonstrated a robust predictive capacity for early recurrence within this patient population.

PSMA PET/CT SUVmax as a prognostic biomarker in patients with metachronous metastatic hormone-sensitive prostate cancer (mHSPC).

Metastatic hormone-sensitive prostate cancer (mHSPC) is treatment-resistant and generally considered incurable. The development of prostate-specific membrane antigen positron emission-computed tomography (PSMA PET/CT) has generated immense expectations due to its diagnostic accuracy in prostate cancer (PCa). PSMA expression of the primary tumor, quantified by SUVmax, is a predictor of oncological outcomes. The role of PSMA-PET/CT SUVmax in metachronous mHSPC treated with ADT plus second-generation antiandrogens (ARSI) is unknown. The main aim of this study was to evaluate 68Ga-PSMA-11expression (SUVmax) as a potential prognostic biomarker in patients with metachronous mHSPC treated with ADT and first or second-generation antiandrogens. A second aim was to determine the association between PSMA SUVmax and PSA response to hormone therapy. Patients diagnosed with metachronous mHSPC between July 2017 and February 2023 who developed biochemical recurrence following radical surgery (with or without salvage radiotherapy and/or ADT) or external radiation therapy (with or without ADT) were included. All patients underwent 68Ga-PSMA-11 PET/CT imaging and the SUVmax value was determined for all measurable locations. The SUVmax value was used for the semiquantitative analysis. The Wilcoxon method was used to compare responders (PSA reduction ≥ 50%) to non-responders (PSA reduction < 50%). The SUVmax value and hormone therapy were evaluated as independent variables relative to the PSA response rate or PSA reduction using the linear regression method. A mixed-effects model (ANOVA) was used for the comparisons. A total of 82 patients were included. Median follow-up was 11.7 months. On the linear regression analysis, patients with a high SUVmax treated with ADT + ARSI showed a greater PSA response (p = 0.034) than those treated with ADT + first-generation antiandrogens. In the mixed-effects model, SUVmax was significant (p = 0.041). On the univariate analysis, PSA at recurrence (HR, 3.2; 95% CI: 1.07-13.6; p = 0.078) and the number of metastases (HR, 4.77; 95% CI 1.1-26.1: p = 0.002) were associated with the type of hormone therapy administered. PSMA-PET/CT SUVmax is a prognostic biomarker that can be used to predict a PSA response to ADT + ARSI in patients with metachronous mHSPC. However, these findings need to be confirmed in larger prospective studies.

Albumin-to-Globulin Ratio Combined with Neutrophil-to-Lymphocyte Ratio as a Prognostic Predictor in Multiple Myeloma with Renal Impairment.

The albumin-to-globulin ratio (AGR) and neutrophil-to-lymphocyte ratio (NLR) have been recently regarded as promising prognostic factors in various malignancies. The present study investigated the prognostic value of combining the AGR and NLR (ANS) for risk assessments in multiple myeloma (MM) with renal impairment (RI). From 2011 to 2018, 79 patients with MM and RI were enrolled in this study. Receiver operating curves (ROCs) were constructed to determine optimal AGR and NLR thresholds for predicting overall survival (OS) and progression-free survival (PFS) during follow up. The prognostic values of AGR, NLR, and ANS were evaluated with Cox regression and Kaplan-Meier methods. We also created a predictive nomogram for prognostic evaluations of OS and PFS, and the predictive accuracy was assessed with a concordance index (c-index). The ROC curves analyses showed that the optimal cut-off levels were 2.27 for NLR and 1.57 for AGR. A high NLR and a high ANS were significantly associated with worse OS and PFS. However, a high NLR combined with a low AGR was associated with worse OS. Multivariate analyses demonstrated that both the NLR and ANS were independent predictors for both OS and PFS and that a low AGR was an independent predictor of a reduced OS. The nomogram accurately predicted OS (c-index: 0.785) and PFS (c-index: 0.786) in patients with MM and RI. ANS may serve as a potential prognostic biomarker in patients with MM and RI. The proposed nomograms may facilitate prognostic predictions for patients with MM and RI.

Transcription factor EHF drives cholangiocarcinoma development through transcriptional activation of glioma-associated oncogene homolog 1 and chemokine CCL2.

Cholangiocarcinoma (CCA) is characterized by rapid onset and high chance of metastasis. Therefore, identification of novel therapeutic targets is imperative. E26 transformation-specific homologous factor (EHF), a member of the E26 transformation-specific transcription factor family, plays a pivotal role in epithelial cell differentiation and cancer progression. However, its precise role in CCA remains unclear. In this study, through in vitro and in vivo experiments, we demonstrated that EHF plays a profound role in promoting CCA by transcriptional activation of glioma-associated oncogene homolog 1 (GLI1). Moreover, EHF significantly recruited and activated tumor-associated macrophages (TAMs) through the C-C motif chemokine 2/C-C chemokine receptor type 2 (CCL2/CCR2) axis, thereby remodeling the tumor microenvironment. In human CCA tissues, EHF expression was positively correlated with GLI1 and CCL2 expression, and patients with co-expression of EHF/GLI1 or EHF/CCL2 had the most adverse prognosis. Furthermore, the combination of the GLI1 inhibitor, GANT58, and CCR2 inhibitor, INCB3344, substantially reduced the occurrence of EHF-mediated CCA. In summary, our findings suggest that EHF is a potential prognostic biomarker for patients with CCA, while also advocating the therapeutic approach of combined targeting of GLI1 and CCL2/CCR2-TAMs to inhibit EHF-driven CCA development.

Programmed Death 1 and Cytotoxic T-Lymphocyte-Associated Protein 4 Gene Expression in Peripheral Blood Mononuclear Cells Can Serve as Prognostic Biomarkers for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly aggressive form of liver cancer with poor prognosis. The lack of reliable biomarkers for early detection and accurate diagnosis and prognosis poses a significant challenge to its effective clinical management. In this study, we investigated the diagnostic and prognostic potential of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression in peripheral blood mononuclear cells (PBMCs) in HCC. PD-1 and CTLA-4 gene expression was analyzed comparatively using PBMCs collected from HCC patients and healthy individuals. The results revealed higher PD-1 gene expression levels in patients with multifocal tumors, lymphatic invasion, or distant metastasis than those in their control counterparts. However, conventional serum biomarkers of liver function do not exhibit similar correlations. In conclusion, PD-1 gene expression is associated with OS and PFS and CTLA-4 gene expression is associated with OS, whereas the serum biomarkers analyzed in this study show no significant correlation with survival in HCC. Hence, PD-1 and CTLA-4 expressed in PBMCs are considered potential prognostic biomarkers for patients with HCC that can facilitate prediction of malignancy, response to currently available HCC treatments, and overall survival.

Low nuclear expression of HIF-hydroxylases PHD2/EGLN1 and PHD3/EGLN3 are associated with poor recurrence-free survival in clear cell renal cell carcinoma.

Hypoxia inducible factors, HIF-1α and HIF-2α, and their main regulators, the prolyl hydroxylase domain proteins (PHDs), mediate cellular response to hypoxia and contribute to tumor progression in clear cell renal cell carcinoma (ccRCC). These biomarkers may improve the value of traditional histopathological features in predicting disease progression after nephrectomy for localized ccRCC and guide patient selection for adjuvant treatments. In this study, we analyzed the associations of PHD2 and PHD3 with histopathological tumor features and recurrence-free survival (RFS) in a retrospective cohort of 173 patients who had undergone surgery for localized ccRCC at Helsinki University Hospital (HUH), Finland. An external validation cohort of 191 patients was obtained from Turku University Hospital (TUH), Finland. Tissue-microarrays (TMA) were constructed using the primary tumor samples. Clinical parameters and follow-up information from 2006 to 2019 were obtained from electronic medical records. The cytoplasmic and nuclear expression of PHD2, and PHD3 were scored based on immunohistochemical staining and their associations with histopathological features and RFS were evaluated. Nuclear PHD2 and PHD3 expression in cancer cells were associated with lower pT-stage and Fuhrman grade compared with negative nuclei. Patients with positive nuclear expression of PHD2 and PHD3 in cancer cells had favorable RFS compared with patients having negative tumors. The nuclear expression of PHD2 was independently associated with a decreased risk of disease recurrence or death from RCC in multivariable analysis. These results were observed in both cohorts. The absence of nuclear PHD2 and PHD3 expression in ccRCC was associated with poor RFS and the nuclear expression of PHD2 predicted RFS regardless of other known histopathological prognostic factors. Nuclear PHD2 and PHD3 are potential prognostic biomarkers in patients with localized ccRCC and should be further investigated and validated in prospective studies.

Identification and validation of a prognostic risk-scoring model for AML based on m7G-associated gene clustering.

Acute myeloid leukemia (AML) patients still suffer from poor 5-year survival and relapse after remission. A better prognostic assessment tool is urgently needed. New evidence demonstrates that 7-methylguanosine (m7G) methylation modifications play an important role in AML, however, the exact role of m7G-related genes in the prognosis of AML remains unclear. The study obtained AML expression profiles and clinical information from TCGA, GEO, and TARGET databases. Using the patient data from the TCGA cohort as the training set. Consensus clustering was performed based on 29 m7G-related genes. Survival analysis was performed by KM curves. The subgroup characteristic gene sets were screened using WGCNA. And tumor immune infiltration correlation analysis was performed by ssGSEA. The patients were classified into 3 groups based on m7G-related genebased cluster analysis, and the differential genes were screened by differential analysis and WGCNA. After LASSO regression analysis, 6 characteristic genes (including CBR1, CCDC102A, LGALS1, RD3L, SLC29A2, and TWIST1) were screened, and a prognostic risk-score model was constructed. The survival rate of low-risk patients was significantly higher than that of high-risk patients (p < 0.0001). The area under the curve values at 1, 3, and 5 years in the training set were 0.871, 0.874, and 0.951, respectively, indicating that this predictive model has an excellent predictive effect. In addition, after univariate and multivariate Cox regression screening, histograms were constructed with clinical characteristics and prognostic risk score models to better predict individual survival. Further analysis showed that the prognostic risk score model was associated with immune cell infiltration. These findings suggest that the scoring model and essential risk genes could provide potential prognostic biomarkers for patients with acute myeloid leukemia.

Association of ctDNA detection and recurrence assessment in patients with neoadjuvant treatment.

The utilization of neoadjuvant therapy is progressively expanding in various clinical settings. However, the absence of a clinically validated biomarker to evaluate the treatment response remains a significant challenge in the field. Circulating tumor DNA (ctDNA) detection, a novel and emerging monitoring approach in the field of oncology, holds promise as a potential prognostic biomarker for patients with cancer. This meta-analysis investigated the clinical significance of ctDNA detection as a predictive tool for cancer recurrence in patients receiving neoadjuvant treatment. A comprehensive systematic literature search was conducted using public databases to identify relevant studies that investigated the association between ctDNA detection and cancer recurrence in patients receiving neoadjuvant treatment. Hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CI) were calculated to assess the relationship between cancer recurrence and relevant factors. Cancer recurrence was considered the primary outcome. A total of 23 studies encompassing 1590 patients across eight different cancer types were included in the final analysis. Positive ctDNA detection was significantly associated with higher cancer recurrence, especially at post-neoadjuvant treatment and post-surgery time points. The risk values for the different cancer categories and geographic areas also differed significantly. Our comprehensive meta-analysis revealed a significant positive correlation between ctDNA detection and a higher risk of cancer recurrence in patients receiving neoadjuvant treatment. In addition, the risk of recurrence was influenced by variations in cancer type, timing of detection, and geographic region. These findings highlight the promising clinical applicability of ctDNA as a prognostic marker and monitoring approach for patients with cancer. However, the precise mechanism is unknown and more evidence is needed for further research.

The value of lymphocyte to monocyte ratio in the prognosis of head and neck squamous cell carcinoma: a meta-analysis.

Although lymphocyte-monocyte ratio (LMR) is a potential prognostic biomarker in many tumor indications, a doubt occurs around its association with head and neck squamous cell carcinoma (HNSCC). We aimed to evaluate the predictive value of LMR in patients with HNSCC. We searched PubMed, Web of Science, EMBASE, and the Cochrane database from inception to May 8, 2023 for systematic review and meta-analysis on LMR and outcomes related to HNSCC development. STATA software was used to estimate the correlation between LMR and prognosis. The risk ratio (hazard ratio, HR) and 95% confidence interval l (CI) for overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS), and progression-free survival (PFS) were calculated, and the association between LMR and OS was further validated by subgroup analysis. The source of heterogeneity with the results of subgroup analysis was analyzed by meta-regression analysis. This meta-analysis was registered at PROSPERO (CRD42023418766). After a comprehensive exploration, the results of 16 selected articles containing 5,234 subjects were evaluated. A raised LMR was connected to improved OS (HR = 1.36% CI [1.14-1.62] P = 0.018), DFS (HR = 0.942, 95% CI [0.631-1.382], P = 0.02), and PFS (HR = 0.932, 95% CI [0.527-1.589], P < 0.022). Subgroup analysis indicated that patients with a low LMR level had a poor prognosis with a critical value of ≥4. The LMR was found to be prognostic for cases with an LMR of <4. The meta-regression analysis showed that the cut-off values and treatment methods were the primary sources of high heterogeneity in patients with HNSCC. Our study suggested that an elevated LMR is a potential prognostic biomarker in patients with HNSCC and could be used to predict patient outcomes.

Identification of LncPVT1 and CircPVT1 as prognostic biomarkers in human colorectal polyps

LncPVT1 and CircPVT1 are isoforms for the PVT1 gene and are associated with cancer progression and carcinogenesis. Our study investigated the expression of LncPVT1 and CircPVT1 in colon adenoma polyps. 40 tissues of colorectal polyps and 40 normal-adjacent tissues (NATs) were taken. The expression of LncPVT1 and CircPVT1 was evaluated through qRael-Time PCR. The relation between expression and features of clinicopathological was explored. The ceRNA network was constructed by LncPVT1 and CircPVT1 and predicted miRNAs and miRNAs targets. Further, hub nodes in this network were determined using the cytoHubba package. Over-expressed LncPVT1 and CircPVT1 were differentiated in polyp and NATs. The expression level of LncPVT1 and CircPVT1 were significantly higher in adenoma polyps than in hyperplastic polyps. The area under the curve of the ROC estimate for the LncPVT1 and CircPVT1 was 0.74 and 0.77, respectively. A positive correlation was observed between the LncPVT1 expression and CircPVT1. Three miRNAs, including hsa-miR-484, hsa-miR-24-3p, hsa-miR-423-5p, and CircPVT1, were detected as ceRNA hub nodes. In this study, expression profiles of LncPVT1 and CircPVT1 were significantly higher in precancerous polyps. In addition, based on our in silico analysis, LncPVT1, CircPVT1/miR-484, miR-24-3p, miR-423-5p/PLAGL2 axis might be involved in colon cancer development. LncPVT1 and CircPVT1 can be prescribed as warning problems as potential prognostic biomarkers in patients with pre-CRC colon polyps.

FRI-404 - A systems medicine approach for the identification of potential prognostic biomarkers in patients with acute decompensation of cirrhosis

FRI-404 - A systems medicine approach for the identification of potential prognostic biomarkers in patients with acute decompensation of cirrhosis

Downregulation of RAB17 have a poor prognosis in kidney renal clear cell carcinoma and its expression correlates with DNA methylation and immune infiltration

BackgroundRAB17 is one of the RAB family members. It has been reported to be closely associated with a variety of tumors and has different roles in various tumors. However, the effect of RAB17 in KIRC remains unclear. Materials and methodsWe analyzed the differential expression of RAB17 in kidney renal clear cell carcinoma (KIRC) tissues and normal tissues using the public databases. The prognostic role of RAB17 in KIRC was analyzed using the Cox regression methods, and a prognostic model was constructed based on the results of the Cox analysis. In addition, further analysis of RAB17 in KIRC was performed in relation to genetic alterations, DNA methylation m6A methylation and immune infiltration. Finally, RAB17 mRNA and protein expression levels were analyzed in tissue samples (KIRC tissues and normal tissues) and cell lines (normal renal tubular cell and KIRC cells), and in vitro functional assays were performed. ResultsRAB17 was low-expressed in KIRC. Downregulation of RAB17 expression is correlated with unfavorable clinicopathological characteristics and a worse prognosis in KIRC. The RAB17 gene alteration in KIRC was primarily characterized by copy number alteration. Six CpG sites of RAB17 DNA methylation levels are higher in KIRC tissues than in normal tissues, and are correlated with RAB17 mRNA expression levels, showing a significant negative correlation. cg01157280 site DNA methylation levels are associated with pathological stage and overall survival, and it may be the only CpG site with independent prognostic significance. Functional mechanism analysis revealed that RAB17 is closely associated with immune infiltration. RAB17 expression was found to be negatively correlated with most immune cell infiltration according to two different methods. Furthermore, most immunomodulators were significantly negatively correlated with RAB17 expression, and significantly positively correlated with RAB17 DNA methylation levels. RAB17 was significantly low expression in KIRC cells and KIRC tissues. In vitro, silencing of RAB17 promoted KIRC cell migration. ConclusionRAB17 can be used as a potential prognostic biomarker for patients with KIRC and for assessing immunotherapy response.

Long non‑coding RNA LINC00460 contributes as a potential prognostic biomarker through its oncogenic role with ANXA2 in colorectal polyps.

Long intergenic non-coding RNA 460 (LINC00460) as a potential oncogene and Annexin A2 (ANXA2) as a promoter in different cancer progression processes was considered. A significant relationship between the LINC00460 and ANXA2 has been recently discovered in colorectal cancer (CRC). Therefore, defining molecular biomarkers accompanied by lesion histopathologic features can be a suggestive prognostic biomarker in precancerous polyps. This study aimed to investigate the elusive expression pattern of ANXA2 and LINC00460 in polyps. The construction of the co-expression and correlation network of LINC00460 and ANXA2 was plotted. LINC00460 and ANXA2 expression in 40 colon polyps was quantified by reverse transcription-real-time polymerase chain reaction. The receiver operating characteristic (ROC) curve was designed for distinguishing the high-risk precancerous lesion from the low-risk. Further, bioinformatics analysis was applied to find the shared MicroRNA-Interaction-Targets (MITs) between ANXA2 and LINC00460, and the associated pathways. ANXA2 has a high co-expression rank with LINC00460 in the lncHUB database. Overexpression of ANXA2 and LINC00460 was distinguished in advanced adenoma polyps compared to the adjacent normal samples. The estimated AUC for ANXA2 and LINC00460 was 0.88 - 0.85 with 93%-90% sensitivity and 81%-70% specificity. In addition, eight MITs were shared between ANXA2 and LINC00460. Enrichment analysis detected several GO terms and pathways, including HIF-1α associated with cancer development. In conclusion, the expression of the ANXA2 and LINC00460 were significantly elevated in pre-cancerous polyps, especially in high-risk adenomas. Collectively, ANXA2 and LINC00460 may be administered as potential prognostic biomarkers in patients with a precancerous large intestine lesion as an alarming issue.

ALDOB represents a potential prognostic biomarker for patients with clear cell renal cell carcinoma.

Previous studies have shown that aldolase B (ALDOB) might play controversial roles in multiple types of cancer, which could act as a cancer-promoting factor or a cancer-inhibiting factor depending on the subtype of the cancer. However, the role of ALDOB in clear cell renal cell carcinoma (ccRCC) patients has not been clearly elucidated. Therefore, this study aimed to comprehensively explore the expression level, prognostic value, functional enrichment, immune infiltration, and N6-methyladenosine (m6A) modification of ALDOB in ccRCC patients. A total of 1,070 ccRCC tissues and 409 normal tissues from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database, and the ArrayExpress database were enrolled to evaluate the expression level and prognostic value of ALDOB in ccRCC. The Kaplan-Meier survival curves and the Log-Rank test were performed to assess the prognostic value. The univariate and multivariate Cox regression analysis were used to identify the independent prognostic predictors in ccRCC patients. In addition, R version 4.2.0 with its suitable packages were used to perform the functional enrichment analysis, immune infiltration analysis, and m6A methylation analysis. Statistical significance was set at the P value <0.05. The expression level of ALDOB was significantly down-regulated in ccRCC compared to normal tissue, and the ALDOB expression level was noticeably correlated with T stage, M stage, and histologic grade of patients with ccRCC. The survival analysis revealed that ALODB was the independent predictor of overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) of ccRCC patients. In addition, the functional enrichment analysis showed that ALDOB and its related genes were mainly involved in the metabolism and metabolic pathways of multiple substances, including glycolysis, gluconeogenesis, and fatty acid degradation. Finally, the immune infiltration analysis and the m6A methylation analysis suggested that ALDOB was closely correlated with the infiltration abundance of immune cells and stromal cells in the tumor microenvironment and several types of m6A regulators in ccRCC. As a potential prognostic biomarker for patients with ccRCC, downregulation of ALDOB was closely associated with the clinicopathological features, poor prognosis, immune infiltration, and m6A modification in ccRCC patients.

FOXP1 inhibits pancreatic cancer growth by transcriptionally regulating IRF1 expression.

FOXP1, known as a Forkhead-box (FOX) family protein, plays an important role in human tumorigenesis. However, the function and molecular mechanism of FOXP1 in pancreatic cancer (PC) remain unclear. Here, we report that PC patients with FOXP1 overexpression had a higher survival rate compared to patients with low- FOXP1 expression. Additionally, high expression of FOXP1 can markedly inhibit the growth of pancreatic cancer in vivo and in vitro, whereas low expression of FOXP1 effectively promoted the tumorigenesis. Mechanistically, FOXP1 could directly bind the IRF1 promoter, which triggered the transcriptional activity of IRF1. Taken together, FOXP1 suppressed PC growth via IRF1-dependent manner, serving as a potential prognostic biomarker for patients with PC.

Comprehensive profiling of EGFR mutation subtypes reveals genomic-clinical associations in non-small-cell lung cancer patients on first-generation EGFR inhibitors

Common sensitizing mutations in epidermal growth factor receptor (cEGFR), including exon 19 deletions (19-Del) and exon 21 L858R substitution, are associated with high sensitivity to EGFR-TKIs in NSCLC patients. The treatment for NSCLC patients with uncommon EGFR (uEGFR) mutations remains a subject of debate due to heterogeneity in treatment responses. In this manuscript, the targeted next-generation sequencing (NGS) data of a large cohort of EGFR-mutated NSCLC patients was assessed to elucidate genomic profiles of tumors carrying cEGFR or uEGFR mutations. The results showed that NSCLC patients with uEGFR mutations were more likely to harbor co-occurring genetic alterations in the Hippo pathway and a higher TMB compared with cEGFR-positive patients. Smoking-related mutations were found to significantly enriched in uEGFR-positive patients. Subgroup analyses were performed to identify potential prognostic biomarkers in patients harboring various EGFR subtype mutations. L858R-positive patients with co-existing ARID2 mutations had shorter progression-free survival (PFS) than those who were L858R- or 19-Del-positive but ARID2-negative (median: 2.3 vs. 12.0 vs. 8.0 months, P = 0.038). Furthermore, mutational profiles, such as top frequently mutated genes and mutational signatures of patients with various EGFR subtype mutations were significantly different. Our study analyzed the mutational landscape of NSCLC patients harboring cEGFR and uEGFR mutations, revealing specific genomic characteristics associated with uEGFR mutations that might explain the poor prognosis of first-generation EGFR-TKIs.

Significance of UGT1A6, UGT1A9, and UGT2B7 genetic variants and their mRNA expression in the clinical outcome of renal cell carcinoma.

UDP-glucuronosyltransferase (UGT) metabolizes a number of endogenous and exogenous substrates. Renal cells express high amounts of UGT; however, the significance of UGT in patients with renal cell carcinoma (RCC) remains unknown. In this study, we profile the mRNA expression of UGT subtypes (UGT1A6, UGT1A9, and UGT2B7) and their genetic variants in the kidney tissue of 125 Japanese patients with RCC (Okayama University Hospital, Japan). In addition, we elucidate the association between the UGT variants and UGT mRNA expression levels and clinical outcomes in these patients. The three representative genetic variants, namely, UGT1A6 541A > G, UGT1A9 i399C > T, and UGT2B7-161C > T, were genotyped, and their mRNA expression levels in each tissue were determined. We found that the mRNA expression of the three UGTs (UGT1A6, UGT1A9, and UGT2B7) are significantly downregulated in RCC tissues. Moreover, in patients with RCC, the UGT2B7-161C > T variant and high UGT2B7 mRNA expression are significantly correlated with preferable cancer-specific survival (CSS) and overall survival (OS), respectively. As such, the UGT2B7-161C > T variant and UGT2B7 mRNA expression level were identified as significant independent prognostic factors of CSS and CSS/OS, respectively. Taken together, these findings indicate that UGT2B7 has a role in RCC progression and may, therefore, represent a potential prognostic biomarker for patients with RCC.

Over-expression of NFYB affects stromal cells reprogramming and predicts worse survival in gastric cancer patients

Gastric cancer (GC) is the fifth most common cancer worldwide and the third most fatal. Cancer-associated fibroblasts (CAFs) play an essential role in promoting the occurrence and development of gastric cancer in all stages. NFYB is highly expressed in multiple tumors and promotes tumor invasion, metastasis, and drug resistance, but its role in the occurrence and development of gastric cancer remains unclear. Hence, we used TCGA, TIMER, Kaplan-Meier Plot, and UALCAN databases to analyze the expression of NFYB in pan-cancers and assess its clinical prognostic value. We found that high expression of NFYB may be a promising prognostic biomarker in patients with gastric cancer. High expression of NFYB was associated with high T stage, high histological grade, diffuse gastric cancer, and early-onset GC. Moreover, High expression of NFYB was associated with CAFs infiltration in the GC microenvironment. The prognosis of GC patients with high expression of NFYB and high infiltration of CAFs was worse. Therefore, NFYB may serve as a potential prognostic biomarker in patients with GC.

Circular Noncoding RNA hsa_circ_0003570 as a Prognostic Biomarker for Hepatocellular Carcinoma.

Circular RNAs (circRNAs) are potential biomarkers owing to their stability, tissue specificity, and abundance. This study aimed to evaluate the clinical significance of hsa_circ_0003570 expression and to investigate its potential as a biomarker in hepatocellular carcinoma (HCC). We evaluated hsa_circ_0003570 expression in 121 HCC tissue samples, its association with clinicopathological characteristics, and overall and progression-free survival. Hsa_circ_0003570 expression was downregulated in HCC tissues. Low hsa_circ_0003570 expression was more common in tumors larger than 5 cm (odds ratio (OR), 6.369; 95% confidence interval (CI), 2.725–14.706; p < 0.001), vessel invasion (OR, 5.128; 95% CI, 2.288–11.494; p < 0.001); advanced tumor-node metastasis stage (III/IV; OR, 4.082; 95% CI, 1.866–8.929; p < 0.001); higher Barcelona Clinic Liver Cancer stage (B/C; OR, 3.215; 95% CI, 1.475–6.993; p = 0.003); and higher AFP (>200 ng/mL; OR, 2.475; 95% CI, 1.159–5.291; p = 0.018). High hsa_circ_0003570 expression was an independent prognostic factor for overall survival (hazard ratio (HR), 0.541; 95% confidence interval (CI), 0.327–0.894; p = 0.017) and progression-free survival (HR, 0.633; 95% CI, 0.402–0.997; p = 0.048). Hsa_circ_0003570 is a potential prognostic biomarker in patients with HCC, and further validation of hsa_circ_0003570 is needed.