The prognostic and immune significance of SLAMF9 in pan-cancer and validation of its role in colorectal cancer
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ABSTRACT:
SUBMITTER: Zhao C
PROVIDER: S-EPMC11297030 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Ras homolog gene family member V (RHOV) is an atypical Rho GTPase that participates in various important cellular processes. Although RHOV has been identified to play an oncogenic role in lung cancer and triple-negative breast cancer, its role in other types of tumors remains unknown. In this study, we investigated the expression of RHOV in pan-cancer analysis using The Cancer Genome Atlas (TCGA) and Gene-Tissue Expression datasets. RHOV mRNA levels were dysregulated in several types of tumors. RHOV expression was identified as an independent prognostic factor in 7 of 33 types of tumors; however, the relationship varied according to tumor type. Higher RHOV expression was associated with a favorable prognosis in kidney renal cell carcinoma and prostate adenocarcinoma, for which RHOV expression was downregulated, whereas RHOV expression was associated with a poor prognosis for patients with adenoid cystic carcinoma, lung adenocarcinoma, pancreatic ductal adenocarcinoma, skin cutaneous melanoma, and uveal melanoma with upregulated RHOV expression. Furthermore, RHOV expression was associated with various clinicopathological parameters in these tumors. RHOV expression showed varied associations with different types of tumor-infiltrating immune cells and demonstrated a potential impact on the response to immunotherapy depending on the cancer type. Additionally, functional enrichment analysis of RHOV-related genes demonstrated a role in a wide range of developmental and immune-related processes. This study provides valuable insights into the role of RHOV in pan-cancer development, indicating its role as a tumor suppressor or oncogene according to the cancer type and tumor microenvironment.
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Project description:F-box protein 5 (FBXO5), an essential subunit of the ubiquitin protein ligase complex, is increasingly recognized to exhibit important biological effects in regulating tumor occurrence and progression. The present research was intended to systematically investigate the latent roles of FBXO5 in prognosis and immunological function across cancers. Pan-cancer analyses of FBXO5 were performed based upon publicly available online databases, mainly including the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), UCSC Xena, cBioPortal, and ImmuCellAI, revealing the possible relationships between FBXO5 and prognosis, DNA methylation, tumor microenvironment (TME), infiltration of immune cells, immune-related genes, immune checkpoints, tumor mutation burden (TMB), and microsatellite instability (MSI). The results suggested that FBXO5 was expressed at a high level in numerous tumor cell lines with significant upregulation in most cancers as opposed to normal tissues. Of note, elevated expression of FBXO5 was significantly related to an unfavorable prognosis in many cancer types. Furthermore, DNA methylation and TME were confirmed to display evident correlation with the expression of FBXO5 in several malignancies. Moreover, FBXO5 expression was remarkably positively correlated with the levels of infiltrating Treg cells and Tcm cells in most tumors, but negatively correlated with tumor-infiltrating CD8+ T cells, NK/NKT cells, and Th2 cells. Meanwhile, FBXO5 was demonstrated to be co-expressed with the genes encoding immune activating and suppressive factors, chemokines, chemokine receptors, and major histocompatibility complex (MHC). Immune checkpoints, TMB, and MSI were also overtly associated with FBXO5 dysregulation among diverse kinds of cancers. Additionally, the enrichment analyses showed close relationships between FBXO5 expression and the processes related to cell cycle and immune inflammatory response. These findings provided a detailed comprehension of the oncogenic function of FBXO5. Because of its crucial roles in cancer immunity and tumorigenesis, FBXO5 may serve as a novel prognostic indicator and immunotherapeutic target for various malignancies.
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Project description:BackgroundAccumulating evidence has demonstrated that microRNA-200s (miR-200a, miR-200b and miR-200c) could serve as promising molecular biomarkers for cancer prognosis. Nevertheless, the associations between miR-200s expression and colorectal cancer (CRC) prognosis remain controversial.MethodsWe applied two mainstream approaches combining meta-analysis and bioinformatics analysis to answer whether miR-200s were associated with the prognosis of CRC patients and why miR-200s could be used as prognostic biomarkers for CRC.ResultsConsequently, low expression of miR-200s was associated with unfavorable overall survival (OS) in CRC patients (HR: 1.09; 95% CI 1.01-1.17; P = 0.025). According to the subgroup analysis, the prognostic role of miR-200s was more significant for tissue samples, large samples, American patients and miR-200a subgroups. Then the target genes of miR-200s were predicted and applied for functional enrichment analyses. The results showed that the target genes of miR-200s were mainly enriched into some vital ontology subjects such as regulation ability, key cell structures and binding function. Moreover, a series of important signaling pathways were identified, which were significantly linked with the initiation and progression of CRC. Additionally, a protein‑protein interaction (PPI) network of miR-200s targets was constructed to screen hub genes and modules. The identified hub genes and modules were validated to be highly involved in the occurrence and development of CRC.ConclusionsCurrent evidences revealed that miR-200s could be promising biomarkers for CRC prognosis. However, the findings still need to be validated with more larger-scale prospective studies and biological experiments before miR-200s could be applied into clinical application.
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Project description:BackgroundMYB proto-oncogene is verified as a transcription factor. Although emerging evidence showed that MYB plays a critical part in tumor progression and immunity, a systematic pan-cancer analysis of MYB still remains to be performed for determining whether MYB could serve as a biomarker for cancer screening, prognosis prediction and accurate therapy design in various human cancers.MethodsIn the present study, we performed qRT-PCR, wound healing assay and transwell assay to validate the expression level and biological function of MYB in bladder cancer. Then, we utilized several open-source databases including UCSC Xena database, TCGA, GTEx, etc. Online tools was used to process the raw data from UCSC Xena database.ResultsWe found that the expression level of MYB is significantly higher in bladder cancer cell lines than urothelial cells. Further experiments confirmed that overexpression of MYB enhanced the ability of migration in bladder cancer. Next, we found that the expression level of MYB is significantly higher in most cancers. Meanwhile, MYB expression was positively or negatively related with the prognosis in different cancer types. In addition, MYB expression is significantly related to immune score and immune cells in most cancer types. Moreover, MYB act as an immunotherapy biomarker superior to several traditional immunotherapy biomarkers. Finally, deep deletion was the most frequent genetic alteration of MYB.ConclusionMYB may serve as a powerful biomarker for tumor screening, prognostic, individualized treatment strategy in a broad range of malignancies.
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Project description:BackgroundBlood-based immune-inflammation indexes have been widely used to predict survival in a variety of cancers. In this research, we seeked to evaluate a novel immune-inflammation marker, named the pan-immune-inflammation value (PIV), in patients with nasopharyngeal carcinoma (NPC) undergoing definitive radiotherapy.MethodsA group of 377 patients with NPC was retrospectived analyzed. Clinical data and laboratory data were collected. Receiver operating characteristic (ROC) curve analysis was performed in order to determine the optimal PIV cut-off value. Survival curves were estimated by Kaplan-Meier method, and prognostic variables were identified using a Cox regression model. Additionally, we developed a nomogram and assessed its acuracy using the concordance index (C-index) and a calibration curve.ResultsThe optimal PIV cut-off value was 146.24 according to ROC analysis. High PIV was related to poorer Eastern Cooperative Oncology Group Performance Status (ECOG PS) score (p = 0.017), more advanced T (p＜0.001) and clinical stages (p = 0.024). In univariate analysis, older Age, poorer ECOG PS, higher Epstein-Barr virus DNA (EBV-DNA), advanced T, N and clinical stage, and higher PIV levels were related to patients' poorer overall survival (OS). Poorer ECOG PS, higher EBV-DNA, later T stage, later clinical stage, and higher PIV were associated with patients' poorer progression free survival (PFS). Male sex and later T stage were associated with patients' poorer locoregional recurrence free survival (LRRFS). Poorer ECOG PS, higher EBV-DNA, later T stage, later clinical stage, and higher PIV were associated with patients' poorer distant metastasis free survival (DMFS). Multivariate analysis demonstrated that PIV was an independent prognostic index for OS (HR 2.231, 95 % CI 1.241-4.011, P = 0.007), PFS (HR 1.664, 95 % CI 1.003-2.760, P = 0.049), and DMFS(HR 2.081, 95 % CI 1.071-4.044, P = 0.031). Nomogram C-indexes for the nomogram of OS were 0.684, and PFS were 0.62, respectively. Survival predictions and actual survival were consistent according to the calibration curve.ConclusionsPre-treatment PIV is a promising biomarker for predicting survival in patients with NPC.
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Project description:Lysosomal dysfunction can drive carcinogenesis. Lysosomal-associated membrane protein 3 (LAMP3), is a member of the Lysosome Associated Membrane Proteins and is involved in the malignant phenotype such as tumour metastasis and drug resistance, while the mechanisms that regulate the malignant progression of tumour remain vague. Our study aims to provide a more systematic and comprehensive understanding of the role of LAMP3 in the progression of various cancers by various databases.We explored the role of LAMP3 in pan-cancer using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database. Multiple online web platforms and software were used for data analysis, including HPA, TIMER, TISIDB, GEPIA, UALCAN, Kaplan-Meier plotter, DAVID and TIGER. The immunohistochemistry was used to quantify the LAMP3 and PD-L1 expression levels in cancer.High LAMP3 expression was found in most cancers and differentially expressed across molecular and immune subtypes. The expression of LAMP3 was involved in the immune-associated processes of Antigen processing and presentation, Th17 cell differentiation, Th1 and Th2 cell differentiation, and the immune-associated pathways of T cell receptor and B cell receptor signalling pathways in most cancers. It also correlated with genetic markers of immunomodulators in various cancers. LAMP3 and PD-L1 expression in BRCA and HNSC tissues was higher than that in corresponding adjacent normal tissues by immunohistochemistry. There is a significant correlation between the expression of LAMP3 and PD-L1.Our study elucidates that LAMP3 has different expression patterns and genetic alteration patterns in different tumours. It is a potential biomarker for immune-related cancer diagnosis, prognosis and efficacy prediction.
| S-EPMC10844704 | biostudies-literature
Project description:BackgroundTo explore the value of preoperative prognostic immune and nutritional index (PINI) in predicting postoperative complications and long-term outcomes in patients with stage I-III colorectal cancer (CRC).MethodsRestricted cubic splines were used to assess the relationship between PINI and survival in patients with CRC. The Kaplan-Meier method and log-rank test were used to plot the survival curves. The Cox proportional hazards model was used to evaluate independent prognostic predictors in patients with CRC. A logistic regression analysis was performed to identify independent predictors of postoperative complications. The least absolute shrinkage and selection operator (LASSO) logistic regression algorithm was used for feature screening.ResultsAn evident positive dose-response relationship between PINI and survival in patients with CRC was identified. Compared with patients with a high PINI, those with a low PINI had worse disease-free survival (DFS) (47.9% vs. 66.9%, p < 0.001) and overall survival (OS) (49.7% vs. 70.2%, p < 0.001). The Cox proportional hazards model revealed that PINI was independently associated with DFS (hazard ratio [HR], 0.823; 95% confidence interval [CI], 0.754-0.898; p < 0.001) and OS (HR, 0.833; 95% CI, 0.761-0.912; p < 0.001) in patients with CRC. In the logistic regression analysis, PINI was an independent factor affecting postoperative complications in patients with CRC (odds ratio, 0.710; 95%CI: 0.610-0.810, p < 0.001). The LASSO logistic regression algorithm was used to screen for effective prognostic variables. Finally, we constructed PINI-based nomograms to predict postoperative 1-5-year PFS, and OS in patients with CRC.ConclusionPINI is an effective biomarker for predicting postoperative complications, DFS, and OS in patients with stage I-III CRC.
| S-EPMC9756500 | biostudies-literature
Project description:BackgroundPrevious studies on the systemic immune-inflammation index (SII), which is based on platelet, neutrophil and lymphocyte counts, as a prognostic marker in patients with colorectal cancer (CRC) yielded inconsistent results. The aim of this study was to evaluate the prognostic and clinicopathological role of SII in CRC via meta-analysis.MethodsA comprehensive literature survey was performed on PubMed, Web of Science, Embase and the Cochrane Library databases to include studies published up to 6 April 2020. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were computed to estimate the prognostic and clinicopathological value of SII in CRC.ResultsA total of 12 studies published between 2016 and 2019 were included in our meta-analysis. The combined analysis showed that high SII levels were significantly associated with worse overall survival (OS; HR = 1.61, 95% CI = 1.21-2.13, p = 0.001) and progression-free survival (HR = 1.74, 95% CI = 1.26-2.39, p = 0.001) in CRC. Moreover, elevated SII was also correlated with poor tumor differentiation (OR = 1.60, 95% CI = 1.27-2.02, p < 0.001), presence of distant metastasis (OR = 2.27, 95% CI = 1.10-4.67, p = 0.026), ECOG PS of 1-2 (OR = 1.98, 95% CI = 1.39-2.84, p < 0.001) and tumor size ⩾5 cm (OR = 1.49, 95% CI = 1.18-1.88, p = 0.001). However, high SII was not significantly associated with sex, tumor location, lymph node metastasis, or age in patients with CRC.ConclusionOur meta-analysis indicated that high SII levels predicted poor prognosis in CRC. In addition, an elevated SII was also associated with clinical factors, implying higher malignancy of the disease.
| S-EPMC7357045 | biostudies-literature