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Renal clear cell carcinoma (ccRCC), is an inflammation-related malignancy with poor therapeutic outcome. Interferon-induced transmembrane protein 2 (IFITM2), an inflammation related gene, is reported to promote tumor progression via inducing cytokine release and lymphatic metastasis. However, IFITM2’s role in ccRCC remains unclear. In this study, we aimed to explore the role of IFITM2 in ccRCC. In vitro studies displayed overexpressed IFITM2 level in tumor tissues, while analysis of 538 cases from TCGA unveiled the correlation of upregulated-IFITM2 with shorter survival. Migration and invasion of ccRCC were inhibited following the downregulation of IFITM2. Cocultured with IFITM2-silenced ccRCC cells, human lymphatic endothelial cells were inhibited in proliferation, migration and tube formation, indicating that lymphangiognesis was contributed by IFITM2 expression. Taken together, IFITM2 promotes ccRCC progression by inducing malignant characteristics and lymphatic metastasis. Therefore, IFITM2 represents a promising novel target for therapy and effective prediction of malignancy of ccRCC.

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the prognosis of HNSCC remains bleak. Numerous studies revealed that the tumor mutation burden (TMB) could predict the survival outcomes of a variety of tumors. Objectives: This study aimed to investigate the TMB and immune cell infiltration in these patients and construct an immune-related genes (IRGs) prognostic model. Methods: The expression data of 546 HNSCC patients were obtained from The Cancer Genome Atlas (TCGA) database. All patients were divided into high- and low- TMB groups, and the relationship between TMB and clinical relevance was further analyzed. The differentially expressed genes (DEGs) were identified using the R software package, limma. Functional enrichment analyses were conducted to identify the significantly enriched pathways between two groups. CIBERSORT algorithm was adopted to calculate the abundance of 22 leukocyte subtypes. The IRGs prognostic model was constructed via the multivariate Cox regression analysis. Results: Missense mutation and single nucleotide variants (SNV) were the most predominant mutation types in HNSCC. TP53, TTN, and FAT1 were the most frequently mutated genes. Patients with high TMB were observed with worse survival outcomes. The functional analysis of TMB associated DEGs showed that the identified DEGs mainly involved in spliceosome, RNA degradation, proteasome, and RNA polymerase pathways. We observed that macrophages, T cells CD8, and T cells CD4 memory were the most commonly infiltrated subtypes of immune cells in HNSCC. Finally, an IRGs prognostic model was constructed, and the AUC of the ROC curve was 0.635. Conclusions: Our results suggest that high TMB is associated with poor prognosis in HNSCC patients. The constructed model has potential prognostic value for the prognosis of these individuals, and it needs to be further validated in large-scale and prospective studies.

BackgroundGrowing evidence suggests that circulating tumor cell (CTC) clusters may be an important factor in the metastatic process, but their role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to characterize the molecular and clinical features of CTC cluster-positive human HCC and to assess its prognostic value in HCC patients.MethodsThe CTCs and CTC clusters were evaluated in 204 HCC patients using CellSearch™ System. The counts of CTCs and CTC clusters were correlated with different clinical features, while their associations with progression-free survival (PFS) and overall survival (OS) were evaluated integrally and hierarchically by Kaplan–Meier estimates or Cox proportional regression analysis. Five cases each of CTC cluster-negative and cluster-positive patients were selected for RNA-sequencing analysis. The results of gene enrichment analysis were further verified using tissue microarray (TMA) by immunohistochemistry (IHC).ResultsCTCs and CTC clusters were detected in 76 (37.3%) and 19 (9.3%) of 204 preoperative samples, respectively. CTC cluster-positive HCC represented an aggressive HCC phenotype with larger tumor size, more frequent microvascular invasion, and higher tumor stages. The survival of HCC patients utilizing CTCs and CTC clusters individually showed prognostic significance, while joint analysis revealed patients in Group III (CTC ≥ 2 and CTC cluster > 0) had the worst outcome. Stratified analysis of outcomes in Barcelona Clinic Liver Cancer (BCLC) and tumor–node–metastasis (TNM) stages indicated that patients with CTC clusters had significantly poorer prognosis in each stage than those without CTC clusters. Moreover, the RNA sequencing and TMA staining results showed that CTC cluster-positive HCCs were usually associated with Wnt/β-catenin signaling activation.ConclusionThe presence of CTC clusters characterizes an aggressive HCC subtype. CTC clusters may be used as a biomarker in predicting the prognosis on each stage of malignancy in HCC, which provides evidence for formulating therapeutic strategies for more precise treatment.

Background Colorectal Cancer (CC), a common disease causing approximately million deaths annually, has been the third most frequent type of malignancy. We aimed to identify gene-specific DNA methylation signature to function as prognostic and predictive markers for CC patient survival. Methods Expression profiles of gene-specific DNA methylation and the corresponding clinical information of 201 CC patients were downloaded from The Cancer Genome Atlas (TCGA) dataset and differentially expressed gene-specific DNA methylation was identified after tumor subtype classification. A risk score model was further built by analyzing the expression data of these gene-specific DNA methylations from the training dataset of CC patients. Results Totally, 214 gene-specific DNA methylations were found to be expressed significantly between different subtypes of CC, including 150 up-regulated and 64 down-regulated ones. Up-regulated gene-specific DNA methylation accounted for 70.1% and the down-regulated gene-specific DNA methylation accounted for 29.9%. Hereinto, six gene-specific DNA methylations were obtained, including methy_vimentin and methy_ TFPI2, which were found significantly correlated with overall survival status of patients with CC. Conclusions With the six gene-specific DNA methylation signatures, patients in the training set were divided into low-risk and high- risk groups. What's more, gene-specific DNA methylation target genes were highly associated with protein phosphorylation, which indicated that further research on phosphorylation of target gene-coding protein might provide new sight on the treatment of CC.

BackgroundBladder cancer (BLCA) is the 11th most common malignancy worldwide. Although significant improvements have been made in screening, diagnosis, and precise management in recent years, the prognosis of BLCA remains bleak.ObjectivesThis study aimed to investigate the prognostic significance of tumor-infiltrating immune cells and construct ceRNA networks in BLCA patients.MethodsThe expression data of BLCA patients were obtained from The Cancer Genome Atlas (TCGA) database. A competing endogenous RNA (ceRNA) network was constructed to identify the hub genes involved in the prognosis of BLCA. The CIBERSORT algorithm was utilized to investigate the infiltration levels of 22 subsets of immune cells. Ultimately, the nomogram was generated to visualize the survival probability of each patient, with the calibration curve being performed to assess its performance. Furthermore, the Pearson correlation test was used to explore the correlation between the identified hub genes in the ceRNA network and the prognostic-related immune cells.ResultsA total of eight elements in the ceRNA network were considered as key members and correlated with the prognosis of BLCA, including ELN, SREBF1, DSC2, TTLL7, DIP2C, SATB1, hsa-miR-20a-5p, and hsa-miR-29c-3p. T cells CD8, T cells follicular helper (Tfh), and neutrophils were identified as independent prognostic factors in BLCA. The co-expression analysis showed that there was a significant correlation between the identified hub genes and immune cells.ConclusionOur results suggest that the mechanism of hsa-miR-29c-3p regulates the expression of ELN and DSC2, and the infiltration of Tfh and neutrophils might play pivotal roles in the progression of BLCA.

Osteosarcoma (OS) is the most common bone malignancy, and is particularly prevalent in children and adolescents. OS is an aggressive tumor with a tendency to metastasize and invade to para-carcinoma tissues. The primary treatment for this tumor is a combination of surgery and chemotherapy. However, the prognosis remains poor due to chemoresistance and early metastasis. Osteopontin (OPN), a multifunctional secreted protein, has emerged as an important potential biomarker for diagnosing and treating cancer. The overexpression of OPN has been found in numerous malignant tumors, including breast, lung, gastric and ovarian cancer, as well as melanoma. Recent studies have suggested that OPN may provide an important function in the diagnosis and treatment of OS. The present review summarizes current knowledge and progress in understanding the potential role of OPN as a biomarker in OS.