• Biomarker
• Clinical applications
• Gastric cancer
• Noncoding RNAs
• lncRNAs

• Humans
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/genetics
• Stomach Neoplasms/therapy
• Prognosis
• RNA, Long Noncoding/genetics
• Biomarkers, Tumor/genetics

• Long noncoding RNA
• XIST
• ZFPM2-AS1
• biomarker
• diagnosis
• gastric cancer
• plasma

• Humans
• RNA, Long Noncoding/blood
• RNA, Long Noncoding/genetics
• Stomach Neoplasms/blood
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/genetics
• Biomarkers, Tumor/blood
• Biomarkers, Tumor/genetics
• Male
• Female
• Middle Aged
• ROC Curve
• Aged
• DNA-Binding Proteins/blood
• DNA-Binding Proteins/genetics
• Adult

Abnormal expression of lncRNAs is relevant to the occurrence and development of gastric cancer (GC), but the significance remains inconclusive. We performed a diagnostic meta-bioinformatics analysis to elucidate the association between lncRNA expression and GC risk.

Published datasets were selected from PubMed, Embase, CNKI, and Web of Science, up to 1st December 2021. The pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated to evaluate the diagnostic value. RNA sequencing data were downloaded for validation.

54 studies with 4671 patients and 4652 matched controls were included in the meta-analysis. The pooled SEN, SPE, PLR, NLR, DOR, and AUC were 0.71, 0.76, 2.9, 0.39, 8, and 0.79, respectively. Subgroup analyses showed that the DOR and AUC of intergenic lncRNAs, circulating lncRNAs, larger sample size (>200), and high-quality (NOS score ≥ 7) groups were superior to antisense lncRNAs, tissue lncRNAs, smaller sample size (≤200), and low-quality (NOS score < 7) groups, respectively. However, only circulating lncRNAs had significantly higher diagnostic utility than that tissue lncRNAs. Nine differentially expressed lncRNAs in the meta-analysis were verified in TCGA-STAD. PVT1 was the most effective single lncRNA, with AUC of 0.949, SEN of 0.808, and SPE of 0.969, while PVT1 and C5orf66-AS1 were the most effective combination, with AUC of 0.972, SEN of 0.941, and SPE of 0.937.

Abnormally expressed lncRNAs, especially circulating lncRNAs, might be potential diagnostic biomarkers for GC risk. A novel combined model of lncRNAs might achieve better GC diagnosis performance.

The aim of the study was to propose a signature based on genes associated with antigen processing and presentation (APscore) to predict prognosis and response to immune checkpoint inhibitors (ICIs) in advanced gastric cancer (aGC).

How antigen presentation-related genes affected the immunotherapy response and whether they could predict the clinical outcomes of the immune checkpoint inhibitor (ICI) in aGC remain largely unknown.

In this study, an aGC cohort (Kim cohort, RNAseq, N=45) treated by ICIs, and 467 aGC patients from seven cohorts were conducted to investigate the value of the APscore predicting the prognosis and response to ICIs. Subsequently, the associations of the APscore with the tumor microenvironment (TME), molecular characteristics, clinical features, and somatic mutation variants in aGC were assessed. The area under the receiver operating characteristic curve (AUROC) of the APscore was analyzed to estimate response to ICIs. Cox regression or Log-rank test was used to estimate the prognosis of aGC patients.

The APscore constructed by principal component analysis algorithms was an effective predictive biomarker of the response to ICIs in the Kim cohort and 467 aGC patients (Kim: AUC =0.85, 95% CI: 0.69–1.00; 467 aGC: AUC =0.69, 95% CI: 0.63–0.74). The APscore also was a prognostic biomarker in 467 aGC patients (HR=1.73, 95% CI: 1.21−2.46). Inhibitory immunity, decreased TMB and low stromal scores were observed in the high APscore group, while activation of immunity, increased TMB, and high stromal scores were observed in the low APscore group. Next, we evaluated the value of several central genes in predicting the prognosis and response to ICIs in aGC patients, and verified them using immunogenic, transcriptomic, genomic, and multi-omics methods. Lastly, a predictive model built successfully discriminated patients with vs. without immunotherapy response and predicted the survival of aGC patients.

The APscore was a new biomarker for identifying high-risk aGC patients and patients with responses to ICIs. Exploration of the APscore and hub genes in multi-omics GC data may guide treatment decisions.

• Humans
• Prognosis
• Antigen Presentation
• Antineoplastic Agents, Immunological/therapeutic use
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/genetics
• Biomarkers, Tumor/genetics
• Mutation
• Immunotherapy/methods
• Immune Checkpoint Inhibitors/therapeutic use
• Tumor Microenvironment

• National Natural Science Foundation of China
• Postdoctoral Research Foundation of China

Long noncoding RNA (lncRNA) ZNFX1-AS1 (ZFAS1) is a newly discovered lncRNA, but its diagnostic value in gastric cancer is unclear.

To investigate the potential role of ZFAS1 in gastric cancer and to evaluate the clinical significance of ZFAS1 as a biomarker for gastric cancer screening.

Quantitative real-time polymerase chain reaction (qRT-PCR) was used to screen for gastric cancer-associated lncRNAs in gastric cancer patients, gastric stromal tumor patients, gastritis or gastric ulcer patients, and healthy controls. Correlations between ZFAS1 expression and clinicopathological features were analyzed. The biological effects of ZFAS1 on the proliferation, migration, and invasion of gastric cancer cells were studied by MTT, colony formation, and transwell mi-gration assays. The potential mechanism of ZFAS1 was demonstrated using enzyme-linked immunosorbent assay and qRT-PCR. The relationship between ZFAS1 and tumorigenesis was demonstrated using in vivo tumor formation assays.

The plasma level of lncRNA ZFAS1 was significantly higher in preoperative patients with gastric cancer than in individuals in the other 4 groups. Increased expression of ZFAS1 was significantly associated with lymph node metastasis, advanced TNM stage, and poor prognosis. ZFAS1 regulated the proliferation, migration, and invasion of gastric cancer cells and regulated the growth of gastric cancer cells in vivo. LIN28 and CAPRIN1 were identified as key downstream mediators of ZFAS1 in gastric cancer cells.

LncRNA ZFAS1 promoted the invasion and proliferation of gastric cancer cells by modulating LIN28 and CAPRIN1 expression, suggesting that ZFAS1 can be used as a potential diagnostic and prognostic biomarker in gastric cancer.

• Long noncoding RNA
• ZNFX1-AS1
• Gastric cancer
• Biomarker
• Invasion
• Proliferation

• Antigens, Neoplasm
• Biomarkers
• Cell Cycle Proteins/metabolism
• Cell Line, Tumor
• Cell Movement/genetics
• Cell Proliferation/genetics
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs/genetics
• Neoplasm Invasiveness/pathology
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• RNA-Binding Proteins
• Stomach Neoplasms/pathology

Investigating molecular biomarkers that accurately predict prognosis is of considerable clinical significance. Accumulating evidence suggests that long non-coding ribonucleic acids (lncRNAs) are frequently aberrantly expressed in colorectal cancer (CRC).

To elucidate the prognostic function of multiple lncRNAs serving as biomarkers in CRC.

We performed lncRNA expression profiling using the lncRNA mining approach in large CRC cohorts from The Cancer Genome Atlas (TCGA) database. Receiver operating characteristic analysis was performed to identify the optimal cutoff point at which patients could be classified into the high-risk or low-risk groups. Based on the Cox coefficient of the individual lncRNAs, we identified a nine-lncRNA signature that was associated with the survival of CRC patients in the training set (n = 175). The prognostic value of this nine-lncRNA signature was validated in the testing set (n = 174) and TCGA set (n = 349). The prognostic models, consisting of these nine CRC-specific lncRNAs, performed well for risk stratification in the testing set and TCGA set. Time-dependent receiver operating characteristic analysis indicated that this predictive model had good performance.

Multivariate Cox regression and stratification analysis demonstrated that this nine-lncRNA signature was independent of other clinical features in predicting overall survival. Functional enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology terms further indicated that these nine prognostic lncRNAs were closely associated with carcinogenesis-associated pathways and biological functions in CRC.

A nine-lncRNA expression signature was identified and validated that could improve the prognosis prediction of CRC, thereby providing potential prognostic biomarkers and efficient therapeutic targets for patients with CRC.

• Colorectal cancer
• Long non-coding ribonucleic acid
• Biomarkers
• Survival prediction
• The Cancer Genome Atlas
• Therapeutic targets

Long non-coding RNAs (lncRNAs) are functional components of the human genome. Recent studies have demonstrated that lncRNAs play essential roles in tumorigenesis, and are involved in cell proliferation, apoptosis, migration and invasion in several types of tumor, including lung cancer. However, the clinical relevance of lncRNA expression in lung cancer remains unknown. The aim of the present study was to investigate the expression pattern of RFPL3 antisense (RFPL3S) and its associations with clinicopathological characteristics in patients with lung cancer. Whether RFPL3S can act as a potential prognostic biomarker for lung cancer was also investigated. RFPL3S expression in tumor samples and cells was assessed using the Oncomine database and the Cancer Cell Line Encyclopedia, respectively. Based on Kaplan-Meier Plotter analyses, the prognostic values of RFPL3S were further evaluated. It was revealed that RFPL3S was highly expressed in lung cancer tissues when compared with normal tissues and was significantly associated with pN factor, pTNM stage and Ki-67 labeling index. In the survival analyses, increased RFPL3S expression was associated with poor survival and was inversely associated with first progression in all patients. These results indicate that RFPL3S may be of clinical significance and may act as a prognostic biomarker in lung cancer.

• RFPL3S
• biomarker
• lncRNA
• lung cancer
• prognosis

• Hepatocellular carcinoma
• chronic hepatitis C
• diagnosis
• exosome
• lncRNA
• miRNA

• Expression
• Gastric cancer
• lncRNA

• autophagy
• exophagy
• exosomes
• hepatocellular carcinoma
• hesperidin

Gastrointestinal cancers (GICs) are a huge threat to human health, which mainly include esophageal, gastric, and colorectal cancers. The purpose of this study was to clarify the prognostic value of long noncoding RNAs (lncRNAs) in GICs. A total of 111 articles were included, and 13103 patients (3123 with esophageal cancer, 4972 with gastric cancer, and 5008 with colorectal cancer) were enrolled in this study. The pooled hazard ratio (HR) values and corresponding 95% confidence interval (95% CI) of overall survival (OS) related to different lncRNA expressions in esophageal, gastric, colorectal, and gastrointestinal cancer patients were 1.92 (1.70–2.16), 1.96 (1.77–2.16), 2.10 (1.87–2.36), and 2.00 (1.87–2.13), respectively. We have identified 74 lncRNAs which were associated closely with poor prognosis of GIC patients, including 58 significantly upregulated lncRNA expression and 16 significantly downregulated lncRNA expression. In addition, 47 of the included studies revealed relative mechanisms and 12 of them investigated the correlation between lncRNAs and microRNAs. Taken together, this meta-analysis supports that specific lncRNAs are significantly related to the prognosis of GIC patients and may serve as novel markers for predicting the prognosis of GIC patients. Furthermore, lncRNAs may have a promising contribution to lncRNA-based targeted therapy and clinical decision-making in the future.

In the last few years, accumulating evidence has indicated that numerous long noncoding RNAs (lncRNAs) are abnormally expressed in gastric cancer (GC) and are associated with the survival of GC patients. This study aimed to conduct a meta-analysis on 19 lncRNAs (AFAP1 antisense RNA 1 [AFAP1-AS1], CDKN2B antisense RNA 1 [ANRIL], cancer susceptibility 15 [CASC15], colon cancer associated transcript 2 [CCAT2], gastric adenocarcinoma associated, positive CD44 regulator, long intergenic noncoding RNA [GAPLINC], H19, imprinted maternally expressed transcript [H19], HOX transcript antisense RNA [HOTAIR], HOXA distal transcript antisense RNA [HOTTIP], long intergenic non-protein coding RNA 673 [LINC00673], metastasis-associated lung adenocarcinoma transcript 1 [MALAT1], maternally expressed 3 [MEG3], promoter of CDKN1A antisense DNA damage activated RNA [PANDAR], Pvt1 oncogene [PVT1], SOX2 overlapping transcript [Sox2ot], SPRY4 intronic transcript 1 [SPRY4-IT1], urothelial cancer associated 1 [UCA1], X inactive specific transcript [XIST], ZEB1 antisense RNA 1 [ZEB1-AS1] and ZNFX1 antisense RNA 1 [ZFAS1]) to systematically estimate their prognostic value in GC.

The qualified literature was systematically searched in PubMed, Web of Science, Embase and Cochrane Database of Systematic Reviews (up to March 16, 2018), and one meta-analysis relating to the relationship between lncRNA expression and overall survival (OS) of GC patients was performed. The only evaluation criterion of survival results was OS.

A total of 6,095 GC patients and 19 lncRNAs from 51 articles were included in the present study. Among the listed 19 lncRNAs, 18 lncRNAs (other than SPRY4-IT1) showed a significantly prognostic value (P<0.05).

This meta-analysis suggested that the abnormally expressed lncRNAs (AFAP1-AS1, ANRIL, CASC15, CCAT2, GAPLINC, H19, HOTAIR, HOTTIP, LINC00673, MALAT1, MEG3, PANDAR, PVT1, Sox2ot, UCA1, XIST, ZEB1-AS1 and ZFAS1) were significantly associated with the survival of GC patients, among which AFAP1-AS1, CCAT2, LINC00673, PANDAR, PVT1, Sox2ot, ZEB1-AS1 and ZFAS1 were strong candidates in predicting the prognosis of GC patients.

• gastric cancer
• long noncoding RNA
• meta-analysis
• prognosis

• HULC
• ZNFX1-AS1
• gastric cancer
• long non-coding RNA
• tumor marker

The current study determined the expression and clinical value of lncRNA AC010761.9 in human gastric adenocarcinoma (GA).

Real-time quantitative reverse transcription (qRT)-PCR was used to detect the level of lncRNA expression in 145 GA tissues and three GA cell lines, and the correlation between its level and clinicopathologic characteristics and potential corresponding mRNA of TNF receptor-associated factor 4 gene (TRAF4) was then evaluated.

Elevated lncRNA AC010761.9 was detected in all 6 GA tissues by previous lncRNA expression profile microarray assay. LncRNA AC010761.9 was over-expressed in 99 of 145 GA tissues (68.3%) with an elevated fold change of up to 35.14 compared to matched paracancerous tissues (p < 0.05), and was also over-expressed in the 3 GA cell lines (MGC803, BGC823, and SGC7901) compared to the normal gastric mucosal epithelial cell line (GES-1 cells; p < 0.05) by qRT-PCR. The elevated expression of this lncRNA was related to tumor size (p = 0.028), degree of differentiation (p = 0.047), and serum carbohydrate antigen (CA19-9) and carcinoembryonic antigen (CEA) concentrations (p = 0.026 and p = 0.037, respectively). Multivariate analysis further confirmed that the expression of lncRNA AC010761.9 was related to the degree of tumor differentiation (p = 0.015). Additionally, the expression of lncRNA AC010761.9 had a positive correlation with the mRNA expression of the potentially associated gene (TRAF4) in GA tissues (r = 0.385, p < 0.01).

LncRNA AC010761.9 may be linked to GA progression and is a potential new biomarker for GA.

The online version of this article (10.1186/s12957-017-1289-y) contains supplementary material, which is available to authorized users.

• Expression and clinical value
• Gastric adenocarcinoma
• lncRNA AC010761.9

• biomarker
• gastric cancer
• gene expression
• lncRNAs
• long noncoding RNAs

• Biomarkers, Tumor/genetics
• Gene Expression Regulation, Neoplastic/genetics
• Humans
• RNA, Long Noncoding/genetics
• Stomach Neoplasms/genetics
• Stomach Neoplasms/pathology

Long non-coding RNAs (lncRNAs) are highlighted as novel cancer biomarkers with great promise. Herein, we focused on summarizing the overall diagnostic performance of lncRNAs for gastric cancer (GC).

Publications fulfilling the search criteria were selected from the online databases. Study quality was assessed according to the Quality Assessment for Studies of Diagnostic Accuracy (QUADAS) checklist. The summary receiver operator characteristic (SROC) curve was plotted using a bivariate meta-analysis model. Statistical analysis was performed based on the platforms of STATA 12.0 and Meta-Disc 1.4 software.

Fifteen studies with 1252 patients and 1283 matched controls were included. The pooled sensitivity and specificity for lncRNA expression profile in differentiating GC patients from cancer-free individuals were 0.68 (95%CI: 0.61-0.74) and 0.79 (95%CI: 0.72-0.84), respectively, corresponding to an area under curve (AUC) of 0.80. Moreover, the stratified analyses demonstrated that plasma-based lncRNA profiling harbored higher accuracy than that tissue-based assay (specificity: 0.80 versus 0.75; AUC: 0.84 versus 0.77).

LncRNA profiling hallmarks a moderate diagnostic value in the management of GC and that lncRNA expression patterns may potentially be utilized as auxiliary biomarkers in confirming GC.

• biomarker
• diagnostic accuracy
• gastric cancer
• lncRNA
• meta-analysis

• Gastric cancer
• MiR-320
• diagnosis
• prognosis

Long non-coding RNAs (lncRNAs) have been identified as novel biomarkers for the diagnosis, staging and prognosis for gastric cancer. However, various studies have reported a series of significances based on different diagnostic values. Therefore, the current study performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of lncRNAs for gastric cancer, and to discuss lncRNA types and sources of heterogeneity. The Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, EMBASE, the Chinese Biomedical Literature Database, the China Academic Journals Full-text Database and the Chinese Scientific Journals Database were systematically searched for potential studies. Studies were included if they were associated with lncRNAs, gastric cancer and reported diagnostic outcomes. Analysis of diagnostic values was used to summarize the overall test performance of lncRNAs. Ten studies were included in this meta-analysis. The ranges of the diagnostic value of lncRNAs for gastric cancer were as follows: Sensitivity was 0.45–0.83, and pooled sensitivity was 0.63; specificity was 0.60–0.93, and pooled specificity was 0.75; positive likelihood ratio was 1.80–6.92, and pooled positive likelihood ratio was 2.51; negative likelihood ratio was 0.23–0.67, and pooled negative likelihood ratio was 0.50; diagnostic odds ratio was 3.33–13.75, and pooled diagnostic odds ratio was 5.47. An overall area under the curve value of the summary receiver operating characteristic curve was 0.7550. LncRNAs did not have a high accuracy for identifying gastric cancer at present, but may be a useful screening tool for diagnosing gastric cancer due to their correlation with gastric cancer biological features. LncRNAs are potential biomarkers for gastric cancer if the screening strategy is altered, or they are combined with other biomarkers to diagnose gastric cancer.

• gastric cancer
• long non-coding RNAs
• meta-analysis
• sensitivity
• specificity

• BM niche
• Cancer stem cell
• Clinical implications
• Leukemia
• Leukemic stem cell
• Surface markers
• ncRNAs

• NONHSAT076754
• biomarker
• lymph node metastasis
• papillary thyroid cancer
• ultrasonography

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor/genetics
• Carcinoma, Papillary/diagnosis
• Carcinoma, Papillary/genetics
• Carcinoma, Papillary/pathology
• Cell Line, Tumor
• Cell Movement/genetics
• Female
• Humans
• Lymph Nodes/pathology
• Lymphatic Metastasis
• Male
• Middle Aged
• Neck
• Neoplasm Invasiveness
• Predictive Value of Tests
• Prognosis
• RNA, Long Noncoding/physiology
• Thyroid Cancer, Papillary
• Thyroid Neoplasms/diagnosis
• Thyroid Neoplasms/genetics
• Thyroid Neoplasms/pathology
• Ultrasonography/methods

• Helicobacter pylori
• gastric cancer
• genotoxicity
• long noncoding RNAs
• stem cells

• Drug resistance
• Long non-coding RNA
• Tumor

• Adriamycin
• Chemotherapy
• Gastric cancer
• Long noncoding RNA
• UCA1

• biomarker
• gastric cancer
• long noncoding RNA
• target therapy

Long noncoding RNAs (lncRNAs) with dysregulated expression levels have been investigated in numerous types of different cancer. Whether lncRNAs can predict the progression of gastric cancer (GC) still remains largely unclear. The aim of our study was to investigate whether KRT18P55, a novel intergenic lncRNA, can be a predictive biomarker for GC.

To determine the expression levels of KRT18P55 in GC, we evaluated it in five GC cell lines (SGC-7901, MGC-803, BGC-823, AGS, and HG27) and 97 GC tissue samples in comparison with a normal control by quantitative polymerase chain reaction. In addition, the association with patient clinicopathological characteristics was analyzed to identify the clinical significance of KRT18P55. We also used publicly accessible data from The Cancer Genome Atlas (TCGA) to further verify the expression levels and clinical significance of KRT18P55. Furthermore, a receiver operating characteristic curve was also conducted to evaluate the diagnostic value of KRT18P55 for GC.

A significant upregulation was observed in GC cell lines (P<0.01) and tissue samples (P<0.01). This finding was consistent with the results of 29 pairs of GC tissue samples from TCGA (P<0.01). Additionally, we indicated that the increased expression of KRT18P55 was related to the progression of intestinal type (P=0.032), which was also supported by results of independent GC cohorts from TCGA (P<0.01). However, we did not find significant difference in prognosis between patients with high and low expression of KRT18P55 (P>0.05). Finally, KRT18P55 showed potential diagnostic value for GC with an area under the receiver operating characteristic curve of 0.733 (P<0.01).

Upregulated KRT18P55 was a novel biomarker for the progression of GC, especially for the intestinal type.

• KRT18P55
• biomarker
• gastric cancer
• intestinal type
• long noncoding RNA

• Bcr-Abl
• CML
• cancer
• lncRNAs
• microRNAs

• Gene Expression Regulation, Neoplastic
• Humans
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology
• RNA, Long Noncoding/genetics

• Biomarker
• Diagnosis
• Gastric cancer
• Long non-coding RNAs
• Prognosis