ST8SIA6-AS1, a novel lncRNA star in liver cancer.

Liver cancer is one of the most lethal gastrointestinal malignancies. Emerging evidence has underscored the pivotal role of long non-coding RNAs (lncRNAs) in tumorigenesis, with ST8SIA6-AS1 identified as a novel oncogenic lncRNA contributing to liver cancer progression. ST8SIA6-AS1 is consistently upregulated in hepatic cancer tissues and is strongly associated with unfavorable prognosis. Moreover, it demonstrates high diagnostic efficacy in detecting HCC. ST8SIA6-AS1 is involved in various cellular processes including proliferation, migration, and invasion, primarily through its function as a competing endogenous RNA (ceRNA), thereby facilitating hepatocarcinogenesis and disease advancement. This review provides a detailed examination of the molecular functions and regulatory mechanisms of ST8SIA6-AS1 in hepatocellular carcinoma (HCC) and highlights its potential as a promising biomarker for liver cancer, aiming to propel the development of innovative therapeutic strategies for HCC management.

Csf1r mediates enhancement of intestinal tumorigenesis caused by inactivation of Mir34a.

The CSF1 receptor (CSF1R) encoding mRNA represents a direct target of miR-34a. However, the in vivo relevance of the suppression of CSF1R by miR-34a for intestinal tumor suppression mediated by the p53/miR-34a pathway has remained unknown. Here, Apc Min/+ mice with intestinal-epithelial cell (IEC)-specific deletions of Mir34a showed increased formation of adenomas and decreased survival, whereas deletion of Csf1r decreased adenoma formation and increased survival. In adenomas deletion of Mir34a enhanced proliferation, STAT3 signaling, infiltration with fibroblasts, immune cells and microbes, and tumor stem cell abundance and decreased apoptosis. Deletion of Csf1r had the opposite effects. In addition, homeostasis of intestinal secretory and stem cells, and tumoroid formation were affected in opposite directions by deletion of Mir34a and CSF1R. Concomitant deletion of Csf1r and Mir34a neutralized the effects of the single deletions. mRNAs containing Mir34a seed-matching sites, which encode proteins related to EMT (epithelial-mesenchymal transition), stemness and Wnt signaling, were enriched after Mir34a inactivation in adenomas and derived tumoroids. Netrin-1/Ntn1 and Transgelin/Tagln were characterized as direct targets of Mir34a and Csf1r signaling. Mir34a-inactivation related expression signatures were associated with CMS4/CRISB+D, stage 4 CRCs and poor patient survival. In tumoroids the loss of Mir34a conferred resistance to 5-FU which was mediated by Csf1r. This study provides genetic evidence for a requirement of Mir34a-mediated Csf1r suppression for intestinal stem/secretory cell homeostasis and tumor suppression, and suggests that therapeutic targeting of CSF1R may be effective for the treatment of CRCs with defects in the p53/miR-34a pathway.

CC Chemokine Receptors in Lung Adenocarcinoma: The Inflammation-Related Prognostic Biomarkers and Immunotherapeutic Targets.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common type of lung cancer with a high incidence and increased mortality. CC chemokine receptors were participating in the modulation of the tumor microenvironment and involved in carcinogenesis and tumor development. However, the potential mechanistic values of CC chemokine receptors as clinical biomarkers and therapeutic targets in LUAD have not been fully clarified. METHODOLOGY: ONCOMINE, UALCAN, GEPIA, Kaplan-Meier Plotter, SurvExpress, MethSurv, SurvivalMeth, cBioPortal, String, GeneMANIA, DAVID, Metascape, TRRUST, LinkedOmics, and Timer were applied in this work. RESULTS: The transcriptional levels of CCR1/10 in LUAD tissues were significantly reduced while the transcriptional levels of CCR3/6/7/8 were significantly elevated, and the expression of CCR1 was the highest in LUAD among these CC chemokine receptors. A significant correlation was found between the expression of CCR2/4/6/7 and the pathological stage of LUAD patients. There were significant associations between CCR2/3/4/5/6/10 expression levels and OS in LUAD, and LUAD patients with high transcriptional levels of CCR3/4 had inferior first-progression survival. In addition, the prognostic values of CC chemokine receptors signature in LUAD were explored in three independent cohorts, the high-risk group displayed unfavorable OS compared with the low-risk group, and the LUAD cases in the high-risk group also suffered inferior RFS than that in the low-risk group. And for the prognostic value of the DNA methylation of CC chemokine receptors, we found 1 CpG of CCR2, 2 CpGs of CCR3, 1 CpG of CCR4, 3 CpGs of CCR6, 3 CpGs of CCR7, 1 CpG of CCR8, and 3 CpGs of CCR9 were significantly associated with prognosis in LUAD patients. However, the DNA methylation signature analysis showed there was no statistically significant association between the high- and low-risk group. For potential mechanism, the neighbor gene networks, interaction analyses, functional enrichment analyses of CC chemokine receptors in LUAD were performed, the transcription factor targets, kinase targets, and miRNA targets of CC chemokine receptors were also identified in LUAD. We also found significant correlations among CC chemokine receptors expression and the infiltration of immune cells, the tumor infiltration levels among LUAD with different somatic copy number alterations of these chemokine receptors were also assessed. Moreover, the Cox proportional hazard model showed that CCR1/2/10, B_cell, CD4_Tcell were significantly related to the clinical outcome of LUAD patients. CONCLUSION: CC chemokine receptors might serve as immunotherapeutic targets and prognostic biomarkers in LUAD.

Identification of Prognostic Biomarkers and Molecular Targets Among JAK Family in Breast Cancer.

BACKGROUND: Janus kinases (JAKs) are a family of non-receptor tyrosine kinases involved in multiple malignancies. However, clinical values of JAKs as prognostic markers and potential mechanism as molecular targets in breast invasive carcinoma (BC) are not completely clarified. METHODOLOGY: TIMER, UALCAN and GEPIA were used to assess the expression and methylation levels of JAKs in BC. Kaplan-Meier Plotter, bc-GenExMiner, SurvExpress, TRGAted, MethSurv, and SurvivalMeth were used to assess the multilevel prognostic significance of JAKs in breast cancer patients. And cBioPortal, TIMER, STRING, GeneMANIA, NetworkAnalysis, LinkedOmics, DAVID 6.8, and Metascape were applied for multilayer networks and functional enrichment analyses. Correlations between immune cell infiltrates/their gene markers and JAKs were evaluated by TIMER. RESULTS: We first explored the expression and methylation level of JAKs in breast cancer and found significantly reduced JAK1 and JAK2 expression at mRNA and protein levels, significantly higher JAK3 protein expression, and significantly increased TYK2 expression at mRNA level but decreased at protein level. In addition, hypermethylation of JAK3 and TYK2 and hypomethylation of JAK1 were found in tumor samples. In terms of prognostic values of JAKs in BC patients, low transcriptional levels of JAK1, JAK2, JAK3, and TYK2 indicated worse OS/DMFS/PPS/RFS/DFS, inferior DFS, worse RFS, and shorter OS/DMFS/RFS, respectively. The mRNA signature analysis showed that high-risk group had unfavorable OS/RFS/MFS. Low JAK2 protein level indicated unfavorable DSS/PFS in BC patients. Five CpGs of JAK1, four CpGs of JAK2, 20 CpGs of JAK3, and 13 CpGs of TYK2 were significantly associated with prognosis in BC patients. The DNA methylation signature analysis also suggested worse prognosis in the high-risk group. For potential biological roles of JAKs, interaction analyses, functional enrichment analyses for biological process, cellular component, molecular function, and KEGG pathway analyses of JAKs and their neighbor genes in BC were conducted. Kinase targets, gene-miRNA interactions, and transcription factor-gene interactions of JAKs were also identified. Furthermore, JAKs were found to be significantly related to immune infiltrates as well as the expression levels of multiple immune markers in BC. CONCLUSION: JAKs showed multilevel prognostic value and important biological roles in BC. They might serve as promising prognostic markers and possible targets in breast cancer.

Prognostic Value of Gastrokine-2 (GKN2) and Its Correlation with Tumor-Infiltrating Immune Cells in Lung Cancer and Gastric Cancers.

BACKGROUND: GKN2, as a secretory protein, is involved in the inflammation and immune modulation, and its aberrant expression is closely related to tumorigenesis. However, integrated studies on the value of GKN2 as a promising clinical biomarker and immunotherapy target in multiple tumors are still rare. METHODOLOGY: Multiple online databases, including ONCOMINE, SEGreg, UALCAN, GEPIA, K-M Plotter, cBioPortal, MethSurv, CellMarker, and Timer, were applied to assess the clinical significance of GKN2 and its correlation with tumor-infiltrating immune cells in differentially expressed cancers. RESULTS: Several databases confirmed that GKN2 was significantly down-regulated in lung and gastric cancers compared that in normal samples. GKN2 was altered in 3%, 5%, and 4% of the LUAD, LUSC, and STAD samples, respectively. Hyper-methylation of GKN2 was found in LUAD and LUSC samples. For the clinical values of GKN2, we found that the low transcription level of GKN2 was associated with worse OS in lung cancer, and inferior FP and PPS in gastric cancer, and the relationships between GKN2 expression and clinical variables regarding OS/FP/PPS in lung and gastric cancers were assessed. Moreover, the prognostic value of the DNA methylation patterns of GKN2 in LUAD, LUSC, and STAD was identified. Furthermore, GKN2 expression was found to be significantly correlated with the infiltrating multiple tumor immune cells, and statistically significant differences in the correlation between GKN2 expression and multiple markers of neutrophils and macrophage polarization were observed in LUAD, LUSC, and STAD. CONCLUSION: The study revealed the prognosis and risk factors for deterioration in patients with low expression of GKN2. GKN2 may be used as a valuable prognostic biomarker and therapeutic target in lung and gastric cancers.

Evidence of the Prognostic Value of Pretreatment Systemic Inflammation Response Index in Cancer Patients: A Pooled Analysis of 19 Cohort Studies.

OBJECTIVE: Systemic inflammation response index (SIRI) is a new inflammation-based evaluation system that has been reported for predicting survival in multiple tumors, but the prognostic significance of SIRI in cancers has not been evinced. METHODS: Eligible studies updated on December 31, 2019, were selected according to inclusion criteria, the literature searching was performed in PubMed, Web of Science, Google Scholar, and Cochrane. Hazard ratios (HRs), and 95% confidence intervals (CIs) were extracted and pooled by using Stata/SE 14.1. RESULTS: 11 publications involving 19 cohort studies with a total of 5,605 subjects were included. Meta-analysis results evinced that high SIRI was associated with worse OS (HR = 2.30, 95% CI: 1.87-2.83, p ≤ 0.001), poor CSS/DSS (HR = 2.83, 95% CI: 1.98-4.04, p ≤ 0.001), and inferior MFS/DFS/PFS/RFS/TTP (HR = 1.88, 95% CI: 1.65-2.15, p ≤ 0.001). The association of SIRI with OS was not significantly affected when stratified by diverse confounding factors. It was suggested that tumor patients with high pretreatment SIRI levels would suffer from adverse outcomes. CONCLUSION: High SIRI is associated with unfavorable clinical outcomes in human malignancies; pretreatment SIRI level might be a useful and promising predictive indicator of prognosis in cancers.

Prognostic significance of peripheral blood-derived neutrophil/lymphocyte ratio in patients with digestive cancer.

Accumulating studies reported the clinical value of derived neutrophil/lymphocyte ratio (dNLR) regarding the prediction of survival outcomes in digestive cancers, however, the prognostic significances of dNLR in these cancers were inconsistent. This study was carried out to clarify the relationship between circulating dNLR and prognosis in gastrointestinal (GI) cancers. Eligible publications were collected and extracted by searching Pubmed, Embase, Web of Science, and Google Scholar up to November 21, 2018. The prognostic impact of dNLR in subjects with GI cancers was assessed with the overall hazard ratios (HRs). A total of 26 studies with up to 13,945 participants were recruited. Our findings showed that peripheral blood dNLR before treatment could be a useful prognostic predictor in digestive cancers, an elevated dNLR indicated a shorter overall survival (OS) in GI tumors (HR, 1.44; 95% confidence interval [CI], 1.36-1.51). Furthermore, its significant prognostic value for OS was also confirmed in subgroup analyses stratified by disease type, publication year, type of research, detection method, geographic location, cut-off value, treatment, analysis type, follow-up time and disease stage. In addition, high dNLR was significantly associated with worse cancer-specific survival (HR, 1.25; 95% CI, 1.04-1.47) and inferior event-free survival (HR, 1.22; 95% CI, 1.11-1.33) in patients with digestive cancers. Our study showed elevated peripheral blood dNLR may indicate unfavorable outcomes in digestive cancer.

Calpain Small Subunit 1 Protein in the Prognosis of Cancer Survivors and Its Clinicopathological Correlation.

Background/Aims. Calpain small subunit 1 (Capn4) is implicated in tumorigenesis and plays a key role in multiple tumors. This study aimed to fully illustrate the prognostic value of Capn4 protein in cancer patients. METHODS: A systematic search was conducted against several online databases. Hazard ratios (HRs) or odds ratio (ORs) were used to investigate the relationship between Capn4 protein expression and prognosis as well as clinical parameters in cancer survivors. RESULTS: Eleven studies involving 1775 patients were identified. Overall, the results showed that Capn4 protein was associated with poor prognosis of overall survival (OS) (HR=1.74; 95% CI:1.47-2.01; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07. CONCLUSIONS: Expression of Capn4 protein is associated with cancer survival and clinicopathologic characteristics in patients.

Deregulated HOXB7 expression predicts poor prognosis of patients with malignancies of digestive system.

INTRODUCTION: Numerous studies have investigated the relationship between deregulated HOXB7 expression with the clinical outcome in patients with digestive stem cancers, HOXB7 has showed negative impacts but with varying levels. We aimed to comprehensively evaluate the prediction and prognostic value of HOXB7 in digestive stem cancers. EVIDENCE ACQUISITION: Electronic databases updated to December 1st, 2016 were retrieved to collect relevant eligible studies to quantitatively explore the potential roles of HOXB7 as a prognostic indicator in digestive system cancers. EVIDENCE SYNTHESIS: A total of 9 studies (N.=1298) was included in this synthetical meta-analysis. The pooled hazard ratios suggested that high expression of HOXB7 protein was associated with poor prognosis of OS in patients with digestive system cancers (HR=1.97, 95% CI: 1.65-2.28, P=0.000), and HOXB7 protein could act as an independent prognostic factor for predicting OS of patients with digestive system cancers (HR=2.02, 95% CI: 1.69-2.36, P=0.000). Statistical significance was also observed in subgroup meta-analysis based on the cancer type, histology type, country, sample size and publication date. Furthermore, we examined the correlations between HOXB7 protein and clinicopathological features. It showed that altered expression of HOXB7 protein was correlated with tumor invasion (P=0.000), lymph node status (P=0.000), distant metastasis (P=0.001) and TNM stage (P=0.000). However, the expression of HOXB7 protein was not associated with age (P=0.64), gender (P=0.40) or levels of differentiation (P=0.19). CONCLUSIONS: High expression of HOXB7 protein was associated with poor prognosis of patients with digestive system cancers, as well as clinicopathologic characteristics, including the tumor invasion, lymph node status, distant metastasis and TNM stage. The expression of HOXB7 protein was not associated with age, gender or levels of differentiation. HOXB7 protein expression level in tumor tissue might serve as a novel prognostic marker for digestive system cancers.