-
Revista Da Associacao Medica Brasileira... 2023Uterine carcinosarcomas are aggressive, rare biphasic tumors with malignant epithelial and malignant sarcomatous components. The prognostic significance of the presence...
OBJECTIVE
Uterine carcinosarcomas are aggressive, rare biphasic tumors with malignant epithelial and malignant sarcomatous components. The prognostic significance of the presence of extrauterine sarcoma (heterologous component) is controversial. Therefore, the aim of this study was to investigate the effect of heterologous components in uterine carcinosarcomas on disease-free survival, overall survival, and other prognostic factors.
METHODS
Clinical and histopathological data from patients treated for uterine carcinosarcoma in a tertiary cancer center in Turkey between July 2000 and January 2020 were collected. Independent risk factors affecting overall survival and disease-free survival were analyzed by univariate and multivariate Cox regression analyses.
RESULTS
A total of 98 patients were identified. The median follow-up was 21.8 (1.2-233.1) months. In the multivariate analysis, the median overall survival and disease-free survival were 23.8 and 20.7 months in those with homologous mesenchymal components and 17.6 and 9.7 months in those with heterologous mesenchymal components, respectively. It was found that the presence of heterologous mesenchymal components significantly reduced both overall survival and disease-free survival (odds ratio [OR], 2.861; 95% confidence interval [CI] 1.196-6.841; p=0.018 and OR, 3.697; 95%CI 1.572-8.695; p=0.003, respectively). In addition, both lymphadenectomy and adjuvant radiotherapy were found to significantly increase overall survival and disease-free survival. Age was found to increase only disease-free survival.
CONCLUSION
The results obtained in this study showed that the presence of heterologous components in uterine carcinosarcoma is a prognostic factor that adversely affects both overall survival and disease-free survival. Lymphadenectomy and adjuvant radiotherapy have beneficial effects on both overall survival and disease-free survival.
Topics: Humans; Prognosis; Disease-Free Survival; Lymph Node Excision; Multivariate Analysis; Carcinosarcoma
PubMed: 37729375
DOI: 10.1590/1806-9282.20230517 -
BMC Cancer Oct 2023Lung adenocarcinoma (LUAD) is a common type of malignant tumor with poor prognosis and high mortality. In our previous studies, we found that estrogen is an important...
Lung adenocarcinoma (LUAD) is a common type of malignant tumor with poor prognosis and high mortality. In our previous studies, we found that estrogen is an important risk factor for LUAD, and different estrogen statuses can predict different prognoses. Therefore, in this study, we constructed a prognostic signature related to estrogen reactivity to determine the relationship between different estrogen reactivities and prognosis. We downloaded the LUAD dataset from The Cancer Genome Atlas (TCGA) database, calculated the estrogen reactivity of each sample, and divided them into a high-estrogen reactivity group and a low-estrogen reactivity group. The difference in overall survival between the groups was significant. We also analyzed the status of immune cell infiltration and immune checkpoint expression between the groups. We analyzed the differential gene expression between the groups and screened four key prognostic factors by the least absolute shrinkage and selection operator (LASSO) regression and univariable and multivariable Cox regression. Based on the four genes, a risk signature was established. To a certain extent, the receiver operating characteristic (ROC) curve showed the predictive ability of the risk signature, which was further verified using the GSE31210 dataset. We also determined the role of estrogen in LUAD using an orthotopic mouse model. Additionally, we developed a predictive nomogram combining the risk signature with other clinical characteristics. In conclusion, our four-gene prognostic signature based on estrogen reactivity had prognostic value and can provide new insights into the development of treatment strategies for LUAD.
Topics: Animals; Mice; Prognosis; Adenocarcinoma of Lung; Nomograms; Estrogens; Lung Neoplasms
PubMed: 37907850
DOI: 10.1186/s12885-023-11415-y -
Frontiers in Immunology 2023Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell lymphoma in adults. CDGSH iron sulfur domain 2 (CISD2) is an iron-sulfur protein and plays a critical...
BACKGROUND
Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell lymphoma in adults. CDGSH iron sulfur domain 2 (CISD2) is an iron-sulfur protein and plays a critical role of cell proliferation. The aberrant expression of CISD2 is associated with the progression of multiple cancers. However, its role in DLBCL remains unclear.
METHODS
The differential expression of CISD2 was identified via public databases, and quantitative real-time PCR (qRT-PCR) and western blot were used to identifed the expression of CISD2. We estimated the impact of CISD2 on clinical prognosis using the Kaplan-Meier plotter. Meanwhile, the drug sensitivity of CISD2 was assessed using CellMiner database. The 100 CISD2-related genes from STRING obtained and analyzed using the LASSO Cox regression. A CISD2 related signature for risk model (CISD2Risk) was established. The PPI network of CISD2Risk was performed, and functional enrichment was conducted through the DAVID database. The impacts of CISD2Risk on clinical features were analyzed. ESTIMATE, CIBERSORT, and MCP-counter algorithm were used to identify CISD2Risk associated with immune infiltration. Subsequently, Univariate and multivariate Cox regression analysis were applied, and a prognostic nomogram, accompanied by a calibration curve, was constructed to predict 1-, 3-, and 5-years survival probabilities.
RESULTS
CISD2 was upregulated in DLBCL patients comparing with normal controls via public datasets, similarly, CISD2 was highly expressed in DLBCL cell lines. Overexpression of CISD2 was associated with poor prognosis in DLBCL patients based on the GSE31312, the GSE32918, and GSE93984 datasets (P<0.05). Nine drugs was considered as a potential therapeutic agents for CISD2. By using the LASSO cox regression, twenty seven genes were identified to construct CISD2Risk, and biological functions of these genes might be involved in apoptosis and P53 signaling pathway. The high CISD2Risk value had a worse prognosis and therapeutic effect (P<0.05). The higher stromal score, immune score, and ESTIMATE score were associated with lowe CISD2Risk value, CISD2Risk was negatively correlated with several immune infiltrating cells (macrophages M0 and M1, CD8 T cells, CD4 naïve T cells, NK cell, etc) that might be correlated with better prognosis. Additionally, The high CISD2Risk was identified as an independent prognostic factor for DLBCL patients using both univariate and multivariate Cox regression. The nomogram produced accurate predictions and the calibration curves were in good agreement.
CONCLUSION
Our study demonstrates that high expression of CISD2 in DLBCL patients is associated with poor prognosis. We have successfully constructed and validated a good prognostic prediction and efficacy monitoring for CISD2Risk that included 27 genes. Meanwhile, CISD2Risk may be a promising evaluator for immune infiltration and serve as a reference for clinical decision-making in DLBCL patients.
Topics: Adult; Humans; Prognosis; Lymphoma, Large B-Cell, Diffuse; Nomograms; Algorithms; Apoptosis
PubMed: 38155967
DOI: 10.3389/fimmu.2023.1277695 -
Scientific Reports Feb 2024Long non-coding RNAs (lncRNAs) involved in metabolism are recognized as significant factors in breast cancer (BC) progression. We constructed a novel prognostic...
Long non-coding RNAs (lncRNAs) involved in metabolism are recognized as significant factors in breast cancer (BC) progression. We constructed a novel prognostic signature for BC using metabolism-related lncRNAs and investigated their underlying mechanisms. The training and validation cohorts were established from BC patients acquired from two public sources: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The prognostic signature of metabolism-related lncRNAs was constructed using the least absolute shrinkage and selection operator (LASSO) cox regression analysis. We developed and validated a new prognostic risk model for BC using the signature of metabolism-related lncRNAs (SIRLNT, SIAH2-AS1, MIR205HG, USP30-AS1, MIR200CHG, TFAP2A-AS1, AP005131.2, AL031316.1, C6orf99). The risk score obtained from this signature was proven to be an independent prognostic factor for BC patients, resulting in a poor overall survival (OS) for individuals in the high-risk group. The area under the curve (AUC) for OS at three and five years were 0.67 and 0.65 in the TCGA cohort, and 0.697 and 0.68 in the GEO validation cohort, respectively. The prognostic signature demonstrated a robust association with the immunological state of BC patients. Conventional chemotherapeutics, such as docetaxel and paclitaxel, showed greater efficacy in BC patients classified as high-risk. A nomogram with a c-index of 0.764 was developed to forecast the survival time of BC patients, considering their risk score and age. The silencing of C6orf99 markedly decreased the proliferation, migration, and invasion capacities in MCF-7 cells. Our study identified a signature of metabolism-related lncRNAs that predicts outcomes in BC patients and could assist in tailoring personalized prevention and treatment plans.
Topics: Humans; Female; Breast Neoplasms; RNA, Long Noncoding; Prognosis; Nomograms; Docetaxel
PubMed: 38347041
DOI: 10.1038/s41598-024-53716-7 -
Nutrients Oct 2023In recent years, the therapeutic effect of monoclonal antibodies against programmed cell death protein-1 (PD-1) in patients with locally advanced or metastatic gastric...
In recent years, the therapeutic effect of monoclonal antibodies against programmed cell death protein-1 (PD-1) in patients with locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) cancer has been confirmed in many studies. The exploration and discovery of new biomarker combinations based on tumor characteristics and tumor microenvironment help screen superior patients and realize precise immunotherapy. As an evaluation index of immunonutritional status, the prognostic nutritional index (PNI) is low cost, simple and easy to obtain, and effective in determining the prognosis of tumor patients. We selected 268 consecutive AGC patients who were treated with ICI therapy from December 2014 to May 2021. We measured their pretreatment of the PNI levels and performed univariate and multivariate Cox regression analyses of progression-free survival (PFS) or overall survival (OS) after ICI therapy. The low pretreatment PNI level of AGC patients was significantly correlated with shorter PFS ( < 0.001) and OS ( < 0.001) after ICI treatment. In univariate and multivariate analyses of the associations between PNI and OS or PFS, PNI is an independent prognostic factor for PFS (HR = 1.511; 95%CI 1.154-1.977; = 0.003) and OS (HR = 1.431; 95%CI 1.049-1.951; = 0.024), respectively. Notably, decreased PNI during treatment with ICIs was associated with early relapse and death. Pretreatment with PNI might help to identify AGC patients who will obtain a survival benefit from ICI therapy.
Topics: Humans; Prognosis; Nutrition Assessment; Stomach Neoplasms; Retrospective Studies; Immunotherapy; Tumor Microenvironment
PubMed: 37836573
DOI: 10.3390/nu15194290 -
Scientific Reports Nov 2023Claudin 18.2 has emerged as a promising therapeutic target in gastric cancer based on phase 3 studies. However, clinicopathologic features associated with claudin 18.2...
Claudin 18.2 has emerged as a promising therapeutic target in gastric cancer based on phase 3 studies. However, clinicopathologic features associated with claudin 18.2 overexpression have not been comprehensively studied specifically for patients with resectable gastric cancer. This retrospective study included 299 patients with stage I-III resectable gastric cancer who underwent curative surgical resection. Possible associations between claudin 18.2 overexpression (moderate-to-strong expression in ≥ 75% by the 43-14A clone) and clinicopathologic features and survival outcomes were analyzed. There were 90 (30.1%), 96 (32.1%), and 113 (37.8%) patients with stage I, II, and III disease, respectively. Claudin 18.2 overexpression was noted in 139 out of 299 patients (46.5%). Claudin 18.2 overexpression was associated with a younger age, a lower invasion depth limited to the mucosa/submucosa, and less frequent lymphovascular invasion. Claudin 18.2 overexpression was also associated with Borrmann type 4 among patients with advanced gastric cancer and the diffuse histological type. Claudin 18.2 overexpression was not an independent factor for survival outcomes. In conclusion, claudin 18.2 was overexpressed in almost half of resectable gastric cancer patients. Claudin 18.2 overexpression was associated with some clinicopathological characteristics, but was not an independent prognostic factor in a localized setting.
Topics: Humans; Prognosis; Stomach Neoplasms; Retrospective Studies; Claudins; Neoplasm Staging; Gastrectomy
PubMed: 37973935
DOI: 10.1038/s41598-023-47178-6 -
Aging Aug 2023Glioma is the most common primary intracranial tumor in the central nervous system, with a high degree of malignancy and poor prognosis, easy to recur, difficult to...
Glioma is the most common primary intracranial tumor in the central nervous system, with a high degree of malignancy and poor prognosis, easy to recur, difficult to cure. The mutation of Retinitis Pigmentosa 2 (RP2) can cause retinitis pigmentosa, it is a prognostic factor of osteosarcoma, however, its role in glioma remains unclear. Based on the data from TCGA and GTEx, we identified RP2 as the most related gene for glioma by WGCNA, and used a series of bioinformatics analyses including LinkedOmics, GSCA, CTD, and so on, to explore the expression of RP2 in glioma and the biological functions it is involved in. The results showed that RP2 was highly expressed in glioma, and its overexpression could lead to poor prognosis. In addition, the results of enrichment analysis showed that RP2 was highly correlated with cell proliferation and immune response. And then, we found significant enrichment of Macrophages among immune cells. Furthermore, our experiments have confirmed that Macrophages can promote the development of glioma by secreting or influencing the secretion of some cytokines. Moreover, we investigated the influence of RP2 on the immunotherapy of glioma and the role of m6A modification in the influence of RP2 on glioma. Ultimately, we determined that RP2 is an independent prognostic factor that is mainly closely related to immune for glioma.
Topics: Humans; Prognosis; Glioma; Retinitis Pigmentosa; Bone Neoplasms; Biomarkers; Membrane Proteins; GTP-Binding Proteins
PubMed: 37602882
DOI: 10.18632/aging.204962 -
Frontiers in Immunology 2023Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide and has a poor prognosis. Thus, there is a need for an effective biomarker...
BACKGROUND
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide and has a poor prognosis. Thus, there is a need for an effective biomarker to improve and predict the prognosis of HCC.
METHODS
RNA sequencing data, simple nucleotide variation data, and clinical data of HCC patients from The Cancer Genome Atlas (TCGA) to identify mutant genes, simple nucleotide variation data, and clinical data of HCC patients from the International Cancer Genome Consortium (ICGC) to validate the prognostic value of mutant genes were the data sources of the present study. To identify the overall survival (OS)-related mutant genes, a Kaplan-Meier (KM) analysis was conducted. We carried out univariate Cox and multivariate Cox regression analyses to identify the independent prognostic factors. We also conducted a correlation analysis of immune cells and mutant genes. To explore the molecular mechanisms of mutant genes, we conducted a gene set enrichment analysis (GSEA). A nomogram was constructed to help predict the prognosis of HCC. In addition, we explored the expression profile of mutant genes in HCC based on a TCGA dataset, an ICGC dataset, and our own HCC tissue samples.
RESULTS
We identified and validated a mutant gene, dynein axonemal heavy chain 5 (), which was negatively related to the OS of HCC patients. Univariate Cox and multivariate Cox regression analyses revealed that the mutant gene could act as an independent prognostic factor for HCC. Most pathways of the mutant gene were involved in cancer development and progression based on GSEA analysis. The mutant gene was negatively correlated with monocytes, naive CD4 T cells, activated dendritic cells, and activated mast cells. In addition, the mRNA and protein levels of had a significantly higher level of expression in the tissue samples of patients with HCC. A nomogram consisting of the pathological stage, , and tumor mutation burden (TMB) performed well.
CONCLUSION
The mutant gene had a significantly higher level of expression in the tissue samples of patients with HCC, could act as an independent prognostic factor for HCC, and is a potential new immunotherapy target for HCC.
Topics: Humans; Carcinoma, Hepatocellular; Prognosis; Liver Neoplasms; Nomograms; Nucleotides; Axonemal Dyneins
PubMed: 38022557
DOI: 10.3389/fimmu.2023.1236995 -
Cancer Medicine Oct 2023Tumor regression grade (TRG) is a measure of histopathological response to neoadjuvant therapy (NAT). Post-therapy lymph node (ypN) metastasis was reported as a...
Tumor regression grade combined with post-therapy lymph node status: A novel independent prognostic factor for patients treated with neoadjuvant therapy followed by surgery in locally advanced gastroesophageal junction and gastric carcinoma.
BACKGROUND
Tumor regression grade (TRG) is a measure of histopathological response to neoadjuvant therapy (NAT). Post-therapy lymph node (ypN) metastasis was reported as a prognostic factor. However, the evaluation of the treatment effectiveness of NAT has not been well studied. Here, we explored whether TRG combined with ypN status could be a prognostic factor for gastroesophageal junction (GEJ) and gastric cancer (GC). Besides, we aimed at making clear the association of different neoadjuvant regimens with different TRG and ypN status.
METHODS
376 patients with GEJ or GC accepting NAT in Peking University Cancer Hospital were retrospectively collected from January 1, 2003 to June 30, 2021. According to TRG and ypN status, patients were innovatively categorized into four groups: TRG0N0, TRG1-3N0, TRG0-1N+, and TRG2-3N+. We applied Kaplan-Meier method and log-rank test to testify the differences in disease free survival (DFS) and overall survival (OS) among four groups. Univariate and multivariate analyses were performed to examine the relationships between TRG combined with ypN status and prognosis.
RESULTS
We observed significant survival differences among the four groups (p < 0.001, respectively). Median DFS and OS of patients with TRG0N0, TRG1-3N0, and TRG0-1N+ were not reached, whereas these of patients with TRG2-3N+ were 17.37 months (95% CI, 14.14-20.60 months) and 39.97 months (95% CI, 27.05-52.89 months). TRG combined with ypN status was still an independent predictor for both DFS (p < 0.001) and OS (p < 0.001) in multivariate analysis. Chi-squared test showed TRG combined with ypN status was significantly associated with different preoperative treatments (p < 0.001). Patients receiving immunotherapy achieved the highest TRG0N0 rate (31.9%).
CONCLUSION
Our results demonstrate that TRG combined with ypN status is a novel independent predictor of both DFS and OS in resectable, locally advanced GEJ and GC. Neoadjuvant immunotherapy achieved the highest TRG0N0 rate.
Topics: Humans; Prognosis; Stomach Neoplasms; Neoadjuvant Therapy; Retrospective Studies; Lymph Nodes; Carcinoma; Esophagogastric Junction; Neoplasm Staging
PubMed: 37749981
DOI: 10.1002/cam4.6597 -
Blood Advances Dec 2023Primary mediastinal B-cell lymphoma (PMBL) is an uncommon entity of aggressive B-cell lymphoma with an unusually good prognosis, except for 10-15% of...
Primary mediastinal B-cell lymphoma (PMBL) is an uncommon entity of aggressive B-cell lymphoma with an unusually good prognosis, except for 10-15% of chemotherapy-refractory cases. To identify earlier these higher risk patients, we performed molecular characterization of a retrospective multicenter cohort of patients treated with firstline immunochemotherapy. The traits of the patients with gene-expression profiling data (n = 120) were as follows: median age of 34 years (range, 18-67 years); female sex, 58.3%; elevated lactate dehydrogenase, 82.5%; Eastern Cooperative Oncology Group performance status score of 0 to 1, 85.7%; Ann Arbor stage I/II, 55%; International Prognostic Index score of 1 to 2, 64.4%; and median metabolic tumor volume, 290.4 cm3 (range, 15.7-1147.5 cm3). Among all 137 markers tested for correlation with survival data, only programmed death-ligand (PDL) 1 and PDL2 expression showed a prognostic impact. Overall, both PDL1 and PDL2 genes were highly expressed in 37 patients (30.8%; PDL1high/PDL2high). The baseline clinical characteristics of patients with PDL1high/PDL2high were similar to those of other patients. In univariate analysis, PDL1high/PDL2high status was associated with poor progression-free survival (PFS) (hazard ratio [HR], 4.292) and overall survival (OS; HR, 8.24). In multivariate analysis, PDL1high/PDL2high status was an independent prognostic factor of adverse outcomes (PFS: HR, 5.22; OS: HR, 10.368). We validated these results in an independent cohort of 40 patients and confirmed the significant association between PDL1high/PDL2high status and inferior PFS (HR, 6.11). High PDL1/PDL2 gene expression defines a population with strong immune privilege and poorer outcomes from standard chemotherapy who might benefit from firstline checkpoint inhibitor therapy.
Topics: Adolescent; Adult; Aged; Female; Humans; Middle Aged; Young Adult; Gene Expression; Lymphoma, Large B-Cell, Diffuse; Prognosis; Progression-Free Survival; Proportional Hazards Models; Male
PubMed: 37862676
DOI: 10.1182/bloodadvances.2023011169