A potential novel biomarker: comprehensive analysis of prognostic value and immune implication of CES3 in colonic adenocarcinoma.

PURPOSE: Colon cancer is the most common malignant tumor in the intestine. Abnormal Carboxylesterases 3 (CES3) expression had been reported to be correlated to multiple tumor progression. However, the association among CES3 expression and prognostic value and immune effects in colonic adenocarcinoma (COAD) were unclear. PATIENTS AND METHODS: The transcription and expression data of CES3 and corresponding clinical information was downloaded from The Cancer Genome Atlas (TCGA). The CES3 protein expression and the prognostic value were verified based on tissue microarray data. The Cancer immune group Atlas (TCIA), Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and the GSE78220 immunotherapy cohort were used to forecast immunotherapy efficacy. Finally, a prognostic immune signature was constructed and verified. RESULTS: Compared with normal colon tissues, the expression of mRNA and protein levels of CES3 were downregulated in tumor tissues. CES3 expression was associated with TIICs. Hihg-CES3 COAD patients had better efficacy of concurrent immunotherapy. CES3-related immune genes (CRIs) were identified and were then used to construct prognostic immune signature and had been successfully verified in GES39582. CONCLUSION: CES3 might be a potential immune-related gene and promising prognostic biomarker in COAD.

Genomic landscape and expression profile of consensus molecular subtype four of colorectal cancer.

Background: Compared to other subtypes, the CMS4 subtype is associated with lacking of effective treatments and poorer survival rates. Methods: A total of 24 patients with CRC were included in this study. DNA and RNA sequencing were performed to acquire somatic mutations and gene expression, respectively. MATH was used to quantify intratumoral heterogeneity. PPI and survival analyses were performed to identify hub DEGs. Reactome and KEGG analyses were performed to analyze the pathways of mutated or DEGs. Single-sample gene set enrichment analysis and Xcell were used to categorize the infiltration of immune cells. Results: The CMS4 patients had a poorer PFS than CMS2/3. CTNNB1 and CCNE1 were common mutated genes in the CMS4 subtype, which were enriched in Wnt and cell cycle signaling pathways, respectively. The MATH score of CMS4 subtype was lower. SLC17A6 was a hub DEG. M2 macrophages were more infiltrated in the tumor microenvironment of CMS4 subtype. The CMS4 subtype tended to have an immunosuppressive microenvironment. Conclusion: This study suggested new perspectives for exploring therapeutic strategies for the CMS4 subtype CRC.

High expression COL10A1 promotes breast cancer progression and predicts poor prognosis.

Background: As a common malignant disease in females, breast cancer (BCa) causes increasing numbers of cancer-related death. Collagen X alpha 1 chain (COL10A1) plays a critical role in the oncogenesis and progression of malignant tumors. However, a systematic analysis of COL10A1 in BCa has not been conducted. Methods: The COL10A1 expression level and prognostic value in BCa were defined through the Cancer Genome Atlas (TCGA) as well as the Kaplan-Meier plotter data respectively. The expression pattern of COL10A1 was subsequently confirmed on tissue microarray (TMA) by immunochemistry (IHC) staining. Moreover, cellular functional assays which aimed to evaluate cell proliferation, migration, invasion, and apoptosis, were conducted to investigate the oncogenic activity of COL10A1 in BCa. Then, Tumor Immune Estimation Resource (TIMER) was adopted to determine the association between COL10A1 expression and immune cell infiltration. Results: Bioinformatics analysis revealed that COL10A1 was significantly overexpressed and had notable prognostic value, especially for distant metastasis-free survival (DMFS) in BCa. Moreover, IHC analysis of 140 BCa tissues on TMA chips exhibited the overexpression of COL10A1 was correlated to advanced clinical stage, poor overall survival (OS), and worse recurrence-free survival (RFS). Besides, knockdown of COL10A1 remarkably suppressed cell proliferation, migration, and invasion in BCa cells, and notably promoted cell apoptosis as well. Furthermore, COL10A1 was positively associated with immune cell infiltration including B cell, CD8+ T cell, CD4+ T cell, macrophage, neutrophil, and dendritic cell. Conclusion: The results revealed that COL10A1 is a novel oncogene and could serve as a potential prognostic biomarker in BCa. Besides, the downregulation of COL10A1 could inhibit BCa progression, which could be a potential target for BCa therapy.

The Clinical Significance of Deglycosylated PD-L1 Level Detection Using 28-8 Monoclonal Antibody in Lung Adenocarcinoma.

Purpose: The aim of this study was to explore the clinical significance of deglycosylated PD-L1 level and its correlation with EGFR and ALK mutation in lung adenocarcinoma. Materials and Methods: We estimated the intensity of both native and deglycosylated PD-L1 signals using a 28-8 antibody on lung adenocarcinoma tissue microarray sections. We analyzed the difference in the H-score between tumor and paratumor tissues, as well as that before and after deglycosylation. Correlations between EGFR or ALK status and PD-L1 expression were analyzed. We also evaluated the differences among survival curves. Results: The expression level of PD-L1 in lung adenocarcinoma tissues was significantly higher than that in paratumor tissues (P<0.0001). Deglycosylation significantly enhanced the detection of PD-L1 in tumor tissues (P<0.0001). There was no statistical significance between the signal intensity of deglycosylated PD-L1 and the survival of patients (P=0.9099). However, the response to deglycosylation of PD-L1 was significantly correlated with the survival of patients with stage N1-N3 (P=0.0435) and stage T3-T4 (P=0.0366) and male patients (P=0.0258). A statistical trend was found in the correlation between the response to deglycosylation of PD-L1 and the survival of patients with grade II-III plus grade III (P=0.0973). Correlation between EGFR or ALK status and the expression of PD-L1 was not found (P>0.05). Conclusion: PD-L1 deglycosylation enhances the detection of PD-L1 when utilizing a 28-8 antibody. Moreover, the response to deglycosylation of PD-L1 may predict the survival of certain patients with lung adenocarcinoma.

Wnt5a: A promising therapeutic target in ovarian cancer.

Despite the rapid development of novel adjuvant and neoadjuvant chemotherapeutic drugs in recent years, advanced ovarian cancer still lacks effective treatment strategies and remains one of the main causes of death among women. Wnt protein family is widely expressed in a variety of human tissues, and Wnt5a is an important member of the noncanonical Wnt pathway. Wnt5a has been found to induce tumor suppression as well as to function as an oncogene depending upon the specific cancer type. In ovarian cancer, Wnt5a protein expression has been observed to be significantly upregulated and associated with poor prognosis. Researchers found that downregulating Wnt5a expression levels effectively suppresses ovarian cancer cell migration and invasion abilities. We believe that the downregulation of Wnt5a will be an attractive and promising antimetastatic therapeutic approach for the future treatment of patients with advanced ovarian cancer. The present review focuses on the mechanisms and therapeutic potential of Wnt5a as a promising novel therapeutic target for ovarian cancer.

A comparability study of natural and deglycosylated PD-L1 levels in lung cancer: evidence from immunohistochemical analysis.

Emerging evidence has revealed that the removal of N-linked glycosylation could enhance PD-L1 detection. However, whether PD-L1 antibodies against different epitopes of PD-L1 antigens responding to deglycosylation has not been characterized. In this study, we compared natural and deglycosylated PD-L1 expression in lung cancer (LuCa) using a panel of PD-L1 antibodies (28-8, CAL10, 73-10 and SP142). We found that removal of N-linked glycosylation markedly enhanced PD-L1 detection when the 28-8, CAL10 and SP142 monoclonal antibodies (mAbs) were used but slightly inhibited PD-L1 detection when the 73-10 mAb was used. Moreover, for the CAL10 and SP142 mAbs, deglycosylated PD-L1 levels showed stronger correlations with the response to anti-PD-1 therapy. Overall, our research provides a comprehensive insight into the application of deglycosylated PD-L1 detection, which expands the clinical significance of this established strategy in LuCa.

Construction of an immune-related gene signature for prediction of prognosis in patients with cervical cancer.

Cervical cancer (CeCa) is becoming an intractable public health issue worldwide. Emerging evidence uncovers that the tumor progression and prognosis of patients with CeCa are tightly associated with the abundance of tumor-infiltrating immune cells. In the current study, the abundance of tumor-infiltrating immune cells in CeCa samples was assessed by using the ssGSEA, thereby generating two immune-related groups according to the immune status. A 4-gene prognostic signature (RIPOR2, DAAM2, SORBS1, and CXCL8) was next established based on the grouping and its predictive capability was validated by multiple analyses. The TIMER database was used to evaluate the association between 4 hub gene expression and immune cell infiltration. Immunophenoscore (IPS) was used to assess response to immune checkpoint inhibitors in CeCa samples. As the results, a novel grouping strategy based on immune cell infiltration was developed and validated. Based on the grouping, a 4-gene signature was identified to be an independent prognostic indicator for overall survival (OS) in CeCa patients. Among the 4 hub genes, RIPOR2 and CXCL8 expression were significantly correlated with immune cell infiltration. Besides, higher immune checkpoints expression and IPS scores were found in the 4-gene signature low-risk group, suggesting a more immunoactive status that tended to respond to immune checkpoint inhibitors. To sum up, a novel immune-related signature is established to predict CeCa patients' prognosis and also associated with response to immune checkpoint inhibitors, which might be a promising prognostic stratification strategy and innovate therapeutic management.

Systematic summarization of the expression profiles and prognostic roles of the dishevelled gene family in hepatocellular carcinoma.

BACKGROUND: Dishevelled (DVL) family members are crucial to Wnt-induced signaling transduction, and their expression is highly correlated with the progression of multiple malignant cancers. However, the expression profiles and exact prognostic values of DVLs in hepatocellular carcinoma (HCC) have not been explored until now. METHODS: The expression of DVL isoforms was assessed using the Oncomine, HCCDB and UALCAN databases. The prognostic roles of DVLs were further evaluated using the GEPIA database. The relationship between the expression of DVLs and immune infiltration of HCC was investigated using the Timer and ImmuCellAI tools. Furthermore, protein-protein interaction (PPI) networks were built and enrichment analyses were conducted. RESULTS: We found that the expression levels of DVL2 (OMIM accession number: 602151) and DVL3 (OMIM accession number: 601368) were upregulated in HCC tissues as revealed by the Oncomine and HCCDB databases. Additionally, the expression of DVLs tended to be associated with advanced clinical features in the UALCAN database. Prognostic analysis revealed that the expression levels of DVL1 (OMIM accession number: 601365) and DVL3 were remarkably associated with a poor prognosis in HCC patients. The results also revealed that the DVL expression level was correlated with the infiltration levels of multiple immune cells. By constructing the PPI network and enrichment analyses, the DVL1-3 gene was identified to interact with 20 key genes and participate in several pathways. CONCLUSION: In summary, DVL2 and DVL3 are highly expressed in HCC, and DVL1 and DVL3 are related to a poor prognosis, which might be used as candidate targets for targeted therapy and reliable prognostic biomarkers in HCC.

The emerging roles of circular RNAs in ovarian cancer.

Circular RNA (circRNA) is a novel class of regulatory noncoding RNA (ncRNA) molecules with a unique covalently closed loop structure. Next-generation sequencing shows that thousands of circRNAs are widely and stably expressed in multiple eukaryotes. As novel regulatory ncRNAs, circRNAs possess several specific molecular functions, including regulating gene transcription and translation, acting as miRNA sponges, and interacting with functional proteins. Ovarian cancer (OvCa) is one of the most aggressive malignant diseases affecting the lives of thousands of women worldwide, and the majority of OvCa cases are diagnosed at advanced stages. Accumulating evidence has revealed the significant roles of circRNAs in the occurrence and progression of OvCa, indicating the function of circRNAs as promising biomarkers and their therapeutic relevance in this disease. This review aims to summarize the mechanisms by which circRNAs mediate OvCa progression as well as their diagnostic and prognostic values in OvCa.