Poor Prognosis For Overall Survival Research Articles

Clinical characteristics and prognosis of patients with newly diagnosed primary central nervous system lymphoma: a multicentre retrospective analysis.

Bruton's tyrosine kinase inhibitors (BTKi) exhibit superior efficacy in relapsed/refractory primary central nervous system lymphoma (PCNSL), but few studies have evaluated patients with newly diagnosed PCNSL, and even fewer studies have evaluated differences in efficacy between treatment with BTKi and traditional chemotherapy. This study retrospectively analyzed the clinical characteristics of 86 patients with PCNSL and identified predictors of poor prognosis for overall survival (OS). After excluding patients who only received palliative care, 82 patients were evaluated for efficacy and survival. According to the induction regimen, patients were divided into the traditional chemotherapy, BTKi combination therapy, and radiotherapy groups; the objective response rates (ORR) of the three groups were 71.4%, 96.2%, and 71.4% (P = 0.037), respectively. Both median progression-free survival and median duration of remission showed statistically significant differences (P = 0.019 and P = 0.030, respectively). The median OS of the BTKi-containing therapy group was also longer than that of the traditional chemotherapy group (not reached versus 47.8 (32.5-63.1) months, P = 0.038).Seventy-one patients who achieved an ORR were further analyzed, and achieved an ORR after four cycles of treatment and maintenance therapy had prolonged OS (P = 0.003 and P = 0.043, respectively). In conclusion, survival, and prognosis of patients with newly diagnosed PCNSL are influenced by the treatment regimen, with the BTKi-containing regimen showing great potential.

RNA splicing regulator EIF3D regulates the tumor microenvironment through immunogene-related alternative splicing in head and neck squamous cell carcinoma.

Study finds that eukaryotic translation initiation factor 3 subunit D (EIF3D) may play an important role in aberrant alternative splicing (AS) events in tumors. AS possesses a pivotal role in both tumour progression and the constitution of the tumour microenvironment (TME). Regrettably, our current understanding of AS remains circumscribed especially in the context of immunogene-related alternative splicing (IGAS) profiles within Head and Neck Squamous Cell Carcinoma (HNSC). In this study, we comprehensively analyzed the function and mechanism of action of EIF3D by bioinformatics analysis combined with in vitro cellular experiments, and found that high expression of EIF3D in HNSC was associated with poor prognosis of overall survival (OS) and progression-free survival (PFS). The EIF3D low expression group had a higher degree of immune infiltration and better efficacy against PD1 and CTLA4 immunotherapy compared to the EIF3D high expression group. TCGA SpliceSeq analysis illustrated that EIF3D influenced differentially spliced alternative splicing (DSAS) events involving 105 differentially expressed immunogenes (DEIGs). We observed an induction of apoptosis and a suppression of cell proliferation, migration, and invasion in EIF3D knock-down FaDu cells. RNA-seq analysis unveiled that 531 genes exhibited differential expression following EIF3D knockdown in FaDu cells. These include 52 DEIGs. Furthermore, EIF3D knockdown influenced the patterns of 1923 alternative splicing events (ASEs), encompassing 129 IGASs. This study identified an RNA splicing regulator and revealed its regulatory role in IGAS and the TME of HNSC, suggesting that EIF3D may be a potential target for predicting HNSC prognosis and immunotherapeutic response.

Prognostic implications of synaptophysin, CD56, thyroid transcription factor-1, and Ki-67 in pulmonary high-grade neuroendocrine carcinomas

BackgroundThe correlation between the expression of immunohistochemical markers and the clinicopathological characteristics of pulmonary high-grade neuroendocrine carcinomas (HGNEC) and its impact on the clinical outcomes of individuals with HGNEC has not yet been explored. MethodsThis study enrolled patients diagnosed with HGNEC between April 2015 and July 2023. Based on the expression levels of synaptophysin (Syn), the neural cell adhesion molecule (CD56), thyroid transcription factor-1 (TTF-1), and Ki-67, a comprehensive analysis was conducted. This involved a comparison of clinicopathological characteristics, chemosensitivity, overall survival (OS), and progression-free survival (PFS). Furthermore, the study identified prognostic factors associated with patient survival through univariate and multivariate analyses. ResultsEighty-two patients were analyzed. Significant differences were identified in tumor stage (χ2 = 5.473, P = 0.019), lymphatic invasion (χ2 = 8.839, P = 0.003), and distant metastasis (χ2 = 5.473, P = 0.019), respectively, between the CD56 positive and negative groups. A significant difference in lymphatic invasion was observed (χ2 = 9.949, P = 0.002) between the CD56 positive and negative groups. A significant difference in vascular invasion was observed (χ2 = 5.106, P = 0.024) between the low and high Ki-67 groups. Compared to the Syn negative group, the Syn positive group had significantly shorter PFS (P = 0.006). Compared to the Syn negative group, the Syn positive group had significantly shorter OS (P = 0.004). The CD56 positive group also had significantly shorter OS than the CD56 negative group (P = 0.027). Univariate analysis revealed that tumor stage and Syn expression were associated with OS and PFS. Lymphatic invasion and CD56 expression were associated with OS. Multivariate analysis revealed that tumor stage was the strongest predictor of poor prognosis for OS (hazard ratio [HR] 0.551, 95 % confidence interval [CI] 0.328–0.927, P = 0.025) and PFS (HR 0.409, 95 % CI 0.247–0.676, P < 0.001). ConclusionsPositive expression of Syn was associated with reduced PFS and OS, while positive CD56 expression was correlated with a shorter OS in HGNEC. The TNM stage was an independent risk factor that significantly influenced PFS and OS in patients with HGNEC. More studies are needed to make further progress in future treatment.

NCOG-13. OUTCOMES OF CNS WHO GRADE 2 OLIGODENDROGLIOMA IN ADULT PATIENTS ; IMPACT OF ADJUVANT TREATMENT ON OVERALL RESULTS

Abstract OBJECTIVE Patients with oligodendroglioma (ODG), isocitrate dehydrogenase (IDH)-mutant, 1p19q codeleted, CNS WHO grade 2 have a median overall survival of longer than 10 years. Patients with ODG who are high-risk by RTOG criteria are offered radiation in combination with procarbazine, lomustine, and vincristine (PCV). The study aims to analyze the patient’s outcomes and assess the efficacy of postoperative treatment. METHODS A total of 138 adult patients who underwent resection for newly diagnosed grade 2 ODG between 1994 and 2021 were enrolled. Sixty-three (45.7%) were observed after gross total resection (GTR) or near total resection (NTR), 5 (0.4%) received adjuvant treatment after GTR or NTR, 37 (26.8%) were observed after subtotal resection (STR) or biopsy, and 33 (24.0%) received adjuvant treatment after STR or biopsy. The study analyzed progression-free survival (PFS), overall survival (OS), and risk variables. RESULTS Out of the 138 patients, 38 (27%) patients received adjuvant treatment, with 30 of them (78.9%) underwent radiotherapy only, 6 (15.8%) underwent radiochemotherapy, and 2 (5.3%) received chemotherapy alone. The median PFS was 6.8 years. Multivariate analysis revealed STR or biopsy (p=0.04), initial MR imaging enhancement (p=0.002), and postoperative observation(p=0.006) were associated with poorer PFS outcomes. The 5-year overall survival rate was 95.5% and the 10-year overall survival was 76.1%. Poor OS prognosis was associated with STR or biopsy (p=0.03), preoperative seizure (p=0.002), and initial MR imaging enhancement (p&amp;lt; 0.001). CONCLUSIONS : GTR and NTR is essential for achieving prolonged PFS and OS in ODG patients. Postoperative treatment is associated with favorable PFS outcomes but does not significantly affect OS. For an accurate diagnosis and appropriate treatment, the utmost care should be taken to avoid underestimating the results of the biopsy.

Outcomes in human T-cell leukemia virus type I carriers after hematopoietic stem cell transplantation for diseases other than adult T cell leukemia/lymphoma: a Japanese national survey

Human T-cell leukemia virus type I (HTLV-1) is a retrovirus known to cause adult T-cell leukemia/lymphoma (ATL). There are few reports on hematopoietic stem cell transplantation (HSCT) for HTLV-1 carriers with diseases other than ATL. A total of 25,839 patients (24,399 adults and 1440 children) with pre-transplant HTLV-1 serostatus information recorded in the Japanese National Survey Database who had undergone their first HSCT were analyzed. We investigated the overall survival (OS), transplant-related mortality (TRM), and disease-related mortality (DRM) after HSCT in relation to HTLV-1 serologic status. Three hundred and forty-eight patients were HTLV-1 antibody carriers. The number of HTLV-1 carriers and noncarriers among adult patients who received allogeneic HSCT (allo-HSCT) or autologous HSCT (auto-HSCT) was 237/15,777 and 95/8920, respectively, and was 16/1424 among pediatric patients who received allo-HSCT. No pediatric HTLV-1 carrier recipients undergoing auto-HSCT were identified. There were no significant differences between HTLV-1 carriers and non-carriers regarding stem cell source, disease risk, or HCT-CI score prior to allo-HSCT. Multivariate analysis of OS (P=0.020) and TRM (P=0.017) in adult patients showed that HTLV-1 positive status was a significant prognostic factor. In children, TRM was significantly higher (P=0.019), but OS was not significantly different. In adult patients who underwent auto-HSCT, HTLV-1 positive status was not a significant prognostic factor. In adult allo-HSCT patients, cytomegalovirus reactivation was significantly more common in HTLV-1 carriers (P=0.001). HTLV-1 antibody positivity was shown to have a poor prognosis in OS and TRM after allo-HSCT in adult patients and in TRM after allo-HSCT in pediatric patients. This work was supported in part by the practical research programs of the Japan Agency for Medical Research and Development (AMED) under grant number 17ck0106342h0001.

Treatment stratification and prognosis assessment using circulating tumor DNA in locally advanced rectal cancer: A systematic review and meta-analysis.

Circulating tumor DNA (ctDNA) is an emerging biomarker for locally advanced rectal cancer (LARC), giving hope for stratified treatment. As the completed studies have small sample sizes and different experimental methods, systematic review and meta-analysis were performed to explore their role in predicting pathological complete response (pCR), tumor recurrence, and prognosis. PubMed, Embase, and the Web of Science were searched for potentially eligible studies published up to September 6, 2022. Pooled relative risk (RR) was calculated to predict pCR and tumor recurrence, and pooled hazard ratio (HR) was calculated to evaluate the prognosis of overall survival (OS), recurrence-free survival (RFS), and metastasis-free survival (MRS). Twelve studies published between 2018 and 2022 included 931 patients, and 2544 serum samples were eventually included in the meta-analysis. The pooled revealed that ctDNA-negative patients were more likely to have a pCR (RR = 1.64, 95% confidence interval [CI]: 1.26-2.12). The pooled revealed that ctDNA-positive patients were at high risk of recurrence (RR = 3.37, 95% CI: 2.34-4.85) and had a poorer prognosis for OS (HR = 3.03, 95% CI: 1.86-4.95), RFS (HR = 7.08, 95% CI: 4.12-12.14), and MRS (HR = 2.77, 95% CI: 2.01-3.83). ctDNA may be useful for stratifying treatment and assessing prognosis in patients with LARC, but its clinical application still needs to be confirmed in a prospective multicenter study with large samples.

A comprehensive analysis of MYO6 as a promising biomarker for diagnosis, prognosis, and immunity in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma. The myosin 6 (MYO6) plays an important role in tumorigenesis and progression. However, its prognostic and immunological effects in ccRCC have not been comprehensively and systematically studied. Therefore, this study aimed to investigate the prognostic value and immune-related role of MYO6 in ccRCC. The expression of MYO6 mRNA and protein in normal and tumor tissues using The Cancer Genome Atlas (TCGA) and other public databases were analyzed. In order to further improve the accuracy of the results, immunohistochemistry (IHC) was performed to verify the results. R software, an integrated repository portal for tumor-immune system interactions (TISIDB) and other online analysis tools were used to investigate the relationship between MYO6 expression and clinicopathological features, diagnostic and prognostic value, and the level of immune infiltration in patients with ccRCC. MYO6 genomic alterations were then investigated using the cBio Cancer Genomics Portal (cBioPortal) database. Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Gene Set Enrichment Analysis (GSEA) enrichment analysis were used to elucidate the biological processes and signaling pathways. Finally, a protein interaction network was constructed using Biological Universal Repository for Interactive Datasets (BioGRID) and some online analysis tools to investigate the correlation between MYO6 and its co-expressed genes in ccRCC patients. In the present study, MYO6 expression was significantly reduced in ccRCC tumors compared with normal tissues.This was consistent with the results of immunohistochemistry. Lower MYO6 expression levels were significantly associated with higher cancer grade and later TNM stage in ccRCC. Compared with the MYO6 high expression group, ccRCC patients with low MYO6 expression had a poor prognosis of overall survival (OS). MYO6 expression has diagnostic and prognostic potential in ccRCC. MYO6 expression is associated with different tumor-infiltrating immune cells, especially macrophages. The findings suggest that reduced MYO6 expression levels are associated with disease progression, poor prognosis, and immune cell infiltration, and can be considered as a promising prognostic biomarker for ccRCC.

High HSPB1 expression predicts poor clinical outcomes and correlates with breast cancer metastasis

BackgroundHeat shock protein beta-1 (HSPB1) is a crucial biomarker for pathological processes in various cancers. However, the clinical value and function of HSPB1 in breast cancer has not been extensively explored. Therefore, we adopted a systematic and comprehensive approach to investigate the correlation between HSPB1 expression and clinicopathological features of breast cancer, as well as determine its prognostic value. We also examined the effects of HSPB1 on cell proliferation, invasion, apoptosis, and metastasis.MethodsWe investigated the expression of HSPB1 in patients with breast cancer using The Cancer Genome Atlas and immunohistochemistry. Chi-squared test and Wilcoxon signed-rank test were used to examine the relationship between HSPB1 expression and clinicopathological characteristics.ResultsWe observed that HSPB1 expression was significantly correlated with the stage N, pathologic stages, as well as estrogen and progesterone receptors. Furthermore, high HSPB1 expression resulted in a poor prognosis for overall survival, relapse-free survival, and distant metastasis-free survival. Multivariable analysis showed that patients with poor survival outcomes had higher tumor, node, metastasis, and pathologic stages. Pathway analysis of HSPB1 and the altered neighboring genes suggested that HSPB1 is involved in the epithelial-to-mesenchymal transition. Functional analysis revealed showed that transient knockdown of HSPB1 inhibited the cell migration/invasion ability and promoted apoptosis.ConclusionsHSPB1 may be involved in breast cancer metastasis. Collectively, our study demonstrated that HSPB1 has prognostic value for clinical outcomes and may serve as a therapeutic biomarker for breast cancer.

Influence of adverse effects of neoadjuvant chemoradiotherapy on the prognosis of patients with early-stage esophageal cancer (cT1b-cT2N0M0) based on the SEER database.

To analyze the prognostic impact of neoadjuvant chemoradiotherapy (NCRT) on early-stage (cT1b-cT2N0M0) esophageal cancer (ESCA) and construct a prognostic nomogram for these patients. We extracted the clinical data about patients diagnosed with early-stage esophageal cancer from the 2004-2015 period of the Surveillance, Epidemiology, and End Results (SEER) database. We applied the independent risk factors affecting the prognosis of patients with early-stage esophageal cancer obtained after screening by univariate and multifactorial COX regression analyses to establish the nomogram and performed model calibration using bootstrapping resamples. The optimal cut-off point for continuous variables is determined by applying X-tile software. After balancing the confounding factors by propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) method, Kaplan-Meier(K-M) curve, and log-rank test were applied to evaluate the prognostic impact of NCRT on early-stage ESCA patients. Among patients who met the inclusion criteria, patients in the NCRT plus esophagectomy (ES) group had a poorer prognosis for overall survival (OS) and esophageal cancer-specific survival (ECSS) than patients in the ES alone group (p < 0.05), especially in patients who survived longer than 1 year. After PSM, patients in the NCRT + ES group had poorer ECSS than patients in the ES alone group, especially after 6 months, while OS was not significantly different between the two groups. IPTW analysis showed that, prior to 6 months patients in the NCRT + ES group had a better prognosis than patients in the ES group, regardless of OS or ECSS, whereas after 6 months, patients in the NCRT + ES group had a poorer prognosis. Based on multivariate COX analysis, we established a prognostic nomogram which showed areas under the ROC curve (AUC) for 3-, 5-, and 10-year OS 0.707, 0.712, and 0.706, respectively, with the calibration curves showing that the nomogram was well calibrated. Patients with early-stage ESCA (cT1b-cT2) did not benefit from NCRT, and we established a prognostic nomogram to provide clinical decision aid for the treatment of patients with early-stage ESCA.

A pan-cancer analysis of the oncogenic role of YKT6 in human tumors.

YKT6, as a Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein with vesicle trafficking, plays an essential role in the development and progression of tumor. However, the gene of YKT6 has not been fully assessed in pan-cancer studies. We aim to investigate the gene of YKT6 across 33 different types of tumor by using the Cancer Genome Atlas, Gene Expression Omnibus database, and other several kinds of bioinformatic tools. YKT6 is significantly up-regulated in most tumors, and we found that overexpression of YKT6 is positively associated with poor prognosis of overall survival and poor disease-free survival prognosis in several tumors, such as Adrenocortical carcinoma, Bladder Urothelial Carcinoma, Head and Neck squamous cell carcinoma. We also detected distinct associations exist between YKT6 and tumor mutational burden or microsatellite instability with tumors. YKT6 expression was positively related to cancer-associated fibroblasts for TCGA tumors of colon adenocarcinoma and LGG. Furthermore, we discovered a significantly positively correlation between YKT6 expression and endothelial cell in tumors of colon adenocarcinoma, HNSC-HPV+, OV, READ and THCA. While a negative relationship was obtained between YKT6 expression and endothelial cell in KIRC. Moreover, "Syntaxin binding," "SNARE complex," "vesicle fusion" and "DNA replication" are involved in the influence of YKT6 on tumor pathogenesis. Our pan-cancer analysis offers a deep comprehending the gene of YKT6 in tumoeigenesis from viewpoint of clinical tumor samples.

Prognostic significance of TMEM131L in glioma and establishment of oxidative stress prognostic model.

Gliomas are the most aggressive of all brain tumors. In this study, it was found that there is a significant expression of transmembrane-like 131 (TMEM131L) in glioma tissues. The relevance of TMEM131L in the diagnosis and clinical prognosis of GBM and LGG was verified by additional clinical correlation and survival analysis. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve reflected the diagnostic effect of TMEM131L on the clinicopathologic features of glioma. As a unique molecular marker for the poor prognosis of overall survival (OS), PFI, and DSS in patients with GCB and LGG, TMEM131L might be employed, according to time-dependent ROC curves and Kaplan-Meier survival analysis at 1, 3, and 5 years. The potential methylation sites of TMEM131L were selected by correlation analysis between TMEM131L and DNA methylation sites. Meanwhile, TMEM131L was significantly correlated with matrix, immunity, and estimated scores of GBM and LGG. The CIBERSORT analysis revealed a significant correlation between immune checkpoint and infiltration of 22 different kinds of immune cells. Coexpression genes of TMEM131L associated with oxidative stress phenotype were screened by the LASSO logistic regression analysis. Nomogram and calibration curves further confirmed that the prognostic model composed of SYT1, CREB3L3, ITPR1, RASGRF2, PDX1, and RASGRF1 has good stability and potential application value for poor prognosis in patients with glioma.

CLDN4 as a Novel Diagnostic and Prognostic Biomarker and Its Association with Immune Infiltrates in Ovarian Cancer.

Ovarian cancer (OC) is the seventh most prevalent type of cancer in women and the second most common cause of cancer-related deaths in women worldwide. Because of the high rates of relapse, there is an immediate and pressing need for the discovery of innovative sensitive biomarkers for OC patients. Using TCGA and GSE26712 datasets, we were able to identify 17 survival-related DEGs in OC that had differential expression. CLDN4 was the gene that caught our attention the most out of the 17 important genes since its expression was much higher in OC samples than in nontumor samples. The findings of the ROC assays then confirmed the diagnostic utility of the test in screening OC specimens to differentiate them from nontumor specimens. Patients with high CLDN4 expression predicted a shorter overall survival (OS) and disease-specific survival (DSS) than those with low CLDN4 expression, according to clinical research. Patients with low CLDN4 expression predicted longer OS and DSS. Analysis using both univariate and multivariate techniques revealed that CLDN4 expression was an independent factor associated with a poor prognosis for OS and DSS. Based on multivariate analysis, the C-indexes and calibration plots of the nomogram suggested an effective predictive performance for OC patients. After that, we investigated whether or not there was a link between the infiltration of immune cells and the expression of the CLDN4 gene. We found that the expression of CLDN4 was positively associated with Th17 cells, NK CD56bright cells, while negatively associated with Th2 cells, pDC, and T helper cells. In the end, we carried out RT-PCR on our cohort and confirmed that the level of CLDN4 expression was noticeably elevated in OC specimens in comparison to nontumor tissues. The diagnostic usefulness of CLDN4 expression for OC was also validated by the findings of ROC tests. Thus, our findings revealed that CLDN4 may serve as a predictive biomarker in OC to assess both the clinical outcome of OC patients and the level of immune infiltration.

Abstract 4463: Prognostic significance of systemic inflammatory markers in recurrent or metastatic head and neck cancer patients treated with nivolumab

Abstract Treatment strategies for head and neck cancer has been improved with the contribution of immunotherapy. In spite of the fact, the mechanisms underlying the response to immune checkpoint inhibitors (ICIs) remain unclear, and discovery of the biomarker predicting therapeutic efficacy of ICIs is urgently required. Our previous study indicated that in patients with recurrent or metastatic head and neck squamous cell carcinoma treated with nivolumab, circulating T cells showed dynamic alterations depending on treatment efficacy using flow cytometry and mass cytometry. However, these analyses are somewhat complicated to apply each patient in clinical setting. In this study, we focused on systemic inflammatory markers, including inflammatory makers such as blood cell fractions and C-reactive protein(CRP) in peripheral blood. Firstly, we assessed the pretreatment systemic inflammatory markers in 61 recurrent or metastatic head and neck cancer patients treated with nivolumab, and determined whether these markers were associated with treatment responses by Kaplan-Meier method, multivariate analysis, regression analysis and classification and regression trees(CART). Next, we investigated circulating T cell subsets in 36 recurrent or metastatic head and neck cancer patients using flow cytometry. High neutrophil to lymphocyte ratio(NLR), platelet to lymphocyte ratio(PLR), and systemic immune-inflammation index(SII) significantly associated with poor prognosis in overall survival (NLR: p=0.0047, PLR: p=0.0357, SII: p=0.0011). Furthermore, high albumin, lymphocyte to monocyte ratio(LMR), and prognostic nutritional index(PNI) were significant good prognostic markers of overall survival (albumin: p=0.0037, LMR: p=0.0088, PNI: p=0.037). Overall survival time were estimated the values that were defined systemic inflammatory markers by multivariate analysis. These systemic inflammatory markers were assigned importance by each coefficient. Notably, the number of monocyte and lymphocyte have a strong influence on overall survival time. In addition, the index that were depending on the number of white blood cells and monocyte, the percentage of lymphocyte, platelet count, albumin, and PNI were useful prognostic tools in analyzing regression analysis. Furthermore, the evaluation of PNI were contributed to the predict treatment efficacy in analyzing CART. Moreover, NLR, PLR, and SII were positively correlated with the proportion of Treg (NLR: R2=0.3622/p=0.0001, PLR: R2=0.4198/p&amp;lt;0.0001, SII: R2=0.3654/p&amp;lt;0.0001). We concluded that in recurrent or metastatic head and neck cancer patients treated with nivolumab, systemic inflammatory markers could provide new insight into rational therapeutic strategies in cancer immunotherapy for head and neck cancer. Citation Format: Hiroe Tada, Kazuaki Chikamatsu. Prognostic significance of systemic inflammatory markers in recurrent or metastatic head and neck cancer patients treated with nivolumab. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4463.

Identification of therapeutic targets and prognostic biomarkers among CC chemokines in the pancreatic adenocarcinoma microenvironment

Pancreatic adenocarcinoma (PAAD), one of the most aggressive and lethal malignant tumors, is correlated with increased morbidity and mortality. CC chemokines can modulate the infiltration of immune cells and affect the clinical outcome of cancer patients. However, the therapeutic potential and prognostic value of CC chemokines in PAAD have not yet been elucidated. To do this, we comprehensively explore and analyze large amounts of data base on ONCOMINE, UALCAN, GEPIA2, LinkedOmics, Kaplan-Meier Plotter, cBioPortal, GeneMANIA, DAVID 6.8, TRRUST, TIMER, TISIDB, DGIdb, and TTD. We found the transcriptional levels of CCL5/7/13/15/18/19/20 in PAAD tissues were remarkably increased, whereas the transcriptional level of CCL17 was decreased. CCL20 expression had significantly been correlated with the tumor stage of PAAD patients. High expressions of CCL5, CCL7, CCL13, CCL18, and CCL20 were notably correlated with the prognosis of patients. Moreover, patients with CCL18 and CCL19 alterations showed a poor prognosis in both overall survival (OS) and disease-specific survival (DSS). Patients with CCL5 and CCL15 alterations also presented a poor prognosis in OS. The key transcription factors for CC chemokines are RELA and NF-κB1. The functions of the differentially expressed CC chemokines were mainly correlated the chemokine signaling pathway, cytokine-cytokine receptor interaction, NF-kappa B signaling pathway, and so forth. We also discovered significant associations between the expression levels of CC chemokines and six infiltrating immune cells including, CD8+ T cells, CD4+ T cells, B cells, macrophages, neutrophils, and dendritic cells. The drug-gene interactions and related miRNAs of aberrant expression CC chemokines were also explored. Our study indicated the correlation between CC chemokines and PAAD and clarified the value of differentially expressed CC chemokines as potential therapeutic targets and prognostic markers for PAAD.

High expression of WTAP is related to poor prognosis in nasopharyngeal carcinoma.

Wilms' tumor 1-associated protein (WTAP), a component of the m6A methyltransferase complex, recruits the m6A methyltransferases METTL3 and METTL14 to the corresponding mRNA targets to participate in the formation of N6-methyladenosine. However, the molecular mechanism of WTAP in the tumorigenesis and progression of nasopharyngeal carcinoma (NPC) remains unclear. This study aimed to explore the prognostic value and biological function of WTAP in NPC. We assessed WTAP expression and its prognostic significance using microarray datasets from the Gene Expression Omnibus (GSE12452) database and 100 NPC tissues via bioinformatics analysis and immunohistochemistry (IHC), respectively. Moreover, gene ontology (GO) and gene set enrichment analysis (GSEA) were performed. In addition, the correlation of WTAP expression with the expression of immune cell biomarkers was analyzed. The results showed that WTAP expression was significantly overexpressed in NPC tissues in GSE12452. The overexpression of WTAP was validated by the external datasets including NPC tissues (GSE150430) and NPC cell lines (GSE39826). GO analysis suggested enrichment in the nucleoplasm (cellular component) and cell cycle (biological process). The GSEA revealed that differentially expressed genes were enriched in E2F-targets, Myc_targets_v1, G2M checkpoint, Myc_targets_v2, and Interferon-alpha-response. In IHC analysis, WTAP was upregulated in NPC tissues, and high levels of WTAP expression were significantly correlated with the advanced T stage (p=0.047) and advanced N stage (p=0.018). Cox regression demonstrated that WTAP overexpression was an independent biomarker of poor prognosis for overall survival (hazard ratio [HR], 4.747; 95% confidence interval [CI], 1.671-13.482; p=0.003). In IHC analysis, the expression of WTAP was positively correlated with CD206 (biomarker for M2 macrophages) (p=0.018) but negatively correlated with CD8a (biomarker for cytotoxic T cells) (p=0.001). In conclusion, WTAP is a promising prognostic biomarker and may participate in the regulation of immune cell infiltration in NPC.

Restratifying the prognosis of acute myeloid leukemia patients with CEBPA double mutations based on CSF3R mutations and measurable residual disease

Objective: This investigation aims to assess the impact of CSF3R mutations and the presence of measurable residual disease (MRD) on the prognosis of patients with CEBPA double mutations who have acute myeloid leukemia (AML) . Methods: The prognostic significance of these two factors was examined in the present study, which included 66 patients with complete genetic mutations and sequential MRD information. Results: Following the second course of chemotherapy, the MRD status and CSF3R mutations of these patients were linked to their long-term prognosis. CSF3R mutated patients showed inferior relapse-free survival (RFS) (5-year RFS: 15.2% vs 38.7% , P=0.006) and overall survival (OS) (5-year OS: 18.2% vs 60.6% , P=0.038) compared with those with wild-type CSF3R. After the second course of chemotherapy, patients with negative MRD had an RFS of 64 months and an OS of not reaching, which was significantly longer than that of patients with positive MRD (15 and 48 months, and the P value were 0.004 and 0.050, respectively) . CSF3R mutations (HR=0.317, 95% CI 0.129-0.779, P=0.012) , WT1 mutations (HR=0.304, 95% CI 0.115-0.804, P=0.016) , and NRAS mutations (HR=0.153, 95% CI 0.061-0.385, P<0.001) were all independently associated with a poor prognosis for RFS, and CSF3R mutations and positive MRD tended to be independently associated with a poor prognosis for OS, according to the results of a Cox proportional-hazards model analysis (P values were 0.071 and 0.088, respectively) . The patients were divided into three groups based on their CSF3R mutation status and MRD status following treatment: wide-type CSF3R and negative MRD, mutated CSF3R or positive MRD, and mutated CSF3R and positive MRD, which showed significantly different RFS (P<0.001) and OS (P=0.006) . Conclusion: Both CSF3R mutations and positive MRD were associated with poor outcome in AML patients with CEBPA double mutations. An integrity model based on these two factors may be beneficial for accurately evaluating the prognosis of these patients.

AMPLIFICATION AND HIGHER EXPRESSION OF THE ZNF281 GENE IN PANCREATIC CANCER CORRELATES WITH POOR PROGNOSIS

Establishing precise gene expression patterns in different cell types is essential for the proper differentiation and development of multicellular organisms. The resulting level of transcription is determined both by the genetic nucleotide sequence of DNA and by epigenetic factors that modify chromatin. Epigenetic repressors of the Polycomb group (PcG) are regulatory proteins that repress gene transcription and maintain correct pattern of gene expression in multicellular organisms. PcG proteins form two main complexes: Polycomb Repressive Complex 1 (PRC1) and Polycomb Repressive Complex 2 (PRC2) that possess ubiquitin ligase and histone methyltransferase enzymatic activities, respectively. Several mechanisms have been suggested to account for the recruitment of Polycomb proteins in mammals, one of which involves interactions with specific DNA-binding factors. While deregulation main PcG genes in cancer have been well documented, the role of PcG DNA-binding partners in oncology remains elusive. In the present study, we analyzed genomic and transcriptomic databases of clinical tumor samples (cBioPortal, TNMplot, KMplot) to evaluate clinical correlations of Polycomb-associated DNA-binding proteins. We found that amplifications and higher expression of the ZNF281 gene are often found in pancreatic cancer and correlate with poor prognosis of overall survival.

Controlling Nutritional Status Score Serves as a Prognosticator in Esophageal Squamous Cell Carcinoma: Optimal Timing of Evaluation of Patients Undergoing Neoadjuvant Treatment.

Usefulness of various nutritional indices for management of patients with esophageal squamous cell carcinoma (ESCC) has been reported. Although Controlling Nutritional Status (CONUT) score is among promising indices to predict outcome, the optimal timing for its measurement during the perioperative period remains unknown. Here the prognostic value of the CONUT score was assessed among patients with ESCC. We analyzed 464 patients who underwent subtotal esophagectomy of ESCC, of which 276 patients were treated with neoadjuvant treatment (NAT). The significance of the associations between candidate parameters including the CONUT score and postoperative prognosis were evaluated. Among the 25 candidate predictors, the preoperative CONUT score had the highest correlation with overall survival (OS) after surgery. Patients were categorized as follows: normal, mild, and moderate or severe, on the basis of the preoperative CONUT score. OS was significantly shortened as the CONUT score worsened. Multivariable analysis revealed that the CONUT scores of the subgroups mild (Hazard ratio [HR] 1.69) and moderate or severe (HR 2.18) were independent predictors of poor prognosis for OS. Furthermore, in an analysis limited to patients who underwent NAT, OS was significantly shortened as the preoperative CONUT score worsened. On the contrary, there was no significant difference in RFS among patient groups stratified by the CONUT score determined before NAT. Our study indicates that the preoperative CONUT score serves as a prognosticator in resectable ESCC. The preoperative CONUT value was more useful than that before NAT in patients administered NAT.

The prognostic role of pre-cystectomy thrombocytosis in invasive bladder cancer.

We aim to evaluate the impact of preoperative thrombocytosis on oncological outcomes in patients with bladder cancer (BC) who undergo radical cystectomy (RC). Retrospective data collection of 1092 patients managed by RC for BC from 2 tertiary-care centers was performed. Elevated platelet count (PLT) was defined as > 450 × 109/L. Univariable and multivariable logistic regression analyses were used to investigate the impact of thrombocytosis on oncological outcomes. These outcomes were also compared using Kaplan-Meier survival analysis. The median follow-up was 50months (32-64months). Thrombocytosis was detected in 18.6% of the patients. The 3-year cancer-specific survival (CSS) for patients with normal PLT count was 92% which was higher than those with elevated PLT count (55%, P < 0.001). Similar results were found for the 6-year CSS with 82% for the no thrombocytosis group and 27% for the thrombocytosis group. Thrombocytosis was still significantly associated with poor prognosis for overall survival and recurrence-free survival (P < 0.001). In the multivariate analysis, CSS was significantly lower in patients with thrombocytosis (HR = 1.71, 95% CI = 1.22-2.39, P = 0.002). Patients with elevated PLT counts were also significantly more likely to receive adjuvant chemotherapy, to have a T stage > pT2b (P = 0.024), to have a positive lymph node, to have variant histology and positive resection margins, and to have concomitant carcinoma in situ (CIS) on final pathology (all P < 0.001). Preoperative thrombocytosis was valuable for predicting the oncological outcomes of patients undergoing RC for BC.

Comprehensive analyses of PDHA1 that serves as a predictive biomarker for immunotherapy response in cancer.

Recent studies have proposed that pyruvate dehydrogenase E1 component subunit alpha (PDHA1), a cuproptosis-key gene, is crucial to the glucose metabolism reprogram of tumor cells. However, the functional roles and regulated mechanisms of PDHA1 in multiple cancers are largely unknown. The Cancer Genome Atlas (TCGA), GEPIA2, and cBioPortal databases were utilized to elucidate the function of PDHA1 in 33 tumor types. We found that PDHA1 was aberrantly expressed in most cancer types. Lung adenocarcinoma (LUAD) patients with high PDHA1 levels were significantly correlated with poor prognosis of overall survival (OS) and first progression (FP). Kidney renal clear cell carcinoma (KIRC) patients with low PDHA1 levels displayed poor OS and disease-free survival (DFS). However, for stomach adenocarcinoma (STAD), the downregulated PDHA1 expression predicted a good prognosis in patients. Moreover, we evaluated the mutation diversity of PDHA1 in cancers and their association with prognosis. We also analyzed the protein phosphorylation and DNA methylation of PDHA1 in various tumors. The PDHA1 expression was negatively correlated with tumor-infiltrating immune cells, such as myeloid dendritic cells (DCs), B cells, and T cells in pan-cancers. Mechanically, we used single-cell sequencing to discover that the PDHA1 expression had a close link with several cancer-associated signaling pathways, such as DNA damage, cell invasion, and angiogenesis. At last, we conducted a co-expressed enrichment analysis and showed that aberrantly expressed PDHA1 participated in the regulation of mitochondrial signaling pathways, including oxidative phosphorylation, cellular respiration, and electron transfer activity. In summary, PDHA1 could be a prognostic and immune-associated biomarker in multiple cancers.