Evaluating the prognostic value of tumor deposits in non-metastatic lymph node-positive colon adenocarcinoma using Cox regression and machine learning.

BACKGROUND: The 8th AJCC TNM staging for non-metastatic lymph node-positive colon adenocarcinoma patients(NMLP-CA) stages solely by lymph node status, irrespective of the positivity of tumor deposits (TD). This study uses machine learning and Cox regression to predict the prognostic value of tumor deposits in NMLP-CA. METHODS: Patient data from the SEER registry (2010-2019) was used to develop CSS nomograms based on prognostic factors identified via multivariate Cox regression. Model performance was evaluated by c-index, dynamic calibration, and Schmid score. Shapley additive explanations (SHAP) were used to explain the selected models. RESULTS: The study included 16,548 NMLP-CA patients, randomized 7:3 into training (n = 11,584) and test (n = 4964) sets. Multivariate Cox analysis identified TD, age, marital status, primary site, grade, pT stage, and pN stage as prognostic for cancer-specific survival (CSS). In the test set, the gradient boosting machine (GBM) model achieved the best C-index (0.733) for CSS prediction, while the Cox model and GAMBoost model optimized dynamic calibration(6.473) and Schmid score (0.285), respectively. TD ranked among the top 3 most important features in the models, with increasing predictive significance over time. CONCLUSIONS: Positive tumor deposit status confers worse prognosis in NMLP-CA patients. Tumor deposits may confer higher TNM staging. Furthermore, TD could play a more significant role in the staging system.

SLC20A1 is a prospective prognostic and therapy response predictive biomarker in head and neck squamous cell carcinoma.

BACKGROUND: SLC20A1, a prominent biomarker in several cancers, has been understudied in its predictive role in head and neck squamous cell carcinoma (HNSCC). METHODS: The Cancer Genome Atlas (TCGA) database was used to analyze HNSCC prognosis, SLC20A1 overexpression, and clinical characteristics. Quantitative real-time PCR and Western blot analysis confirmed SLC20A1 expression in HNSCC tissues. Cellular behaviors such as invasion, migration and proliferation were assessed using Transwell, wound healing and colony formation assays. Immune system data were obtained from the Tumor Immune Estimation Resource (TIMER) and CIBERSORT databases. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore biological parameters and pathways associated with SLC20A1 overexpression in HNSCC. RESULTS: In 499 HNSCC samples, SLC20A1 mRNA and protein expression were significantly higher than in 44 normal counterparts, confirmed by 24 paired samples. Patients were categorized based on SLC20A1 levels, survival status and overall survival. High SLC20A1 expression correlated with advanced T stage, increased risk scores and decreased survival. Stage, age and SLC20A1 expression emerged as independent predictive factors for HNSCC in univariate and multivariate analyses. SLC20A1 overexpression, which is associated with poor prognosis, may influence cell proliferation, migration, invasion, chemotherapy response, and the immune milieu. CONCLUSIONS: SLC20A1 overexpression in HNSCC, characterized by increased cellular invasion, migration and proliferation, is a potential prognostic biomarker and therapeutic response indicator.

Adjuvant medial versus entire supraclavicular lymph node irradiation in high-risk early breast cancer (SUCLANODE): a protocol for a multicenter, randomized, open-label, phase 3 trial.

BACKGROUND: Supraclavicular nodal (SCL) irradiation is commonly used for patients with high-risk breast cancer after breast surgery. The Radiation Therapy Oncology Group (RTOG) and European Society for Radiotherapy and Oncology (ESTRO) breast contouring atlases delineate the medial part of the SCL region, while excluding the posterolateral part. However, recent studies have found that a substantial proportion of SCL failures are located in the posterolateral SCL region, outside of the RTOG/ESTRO-defined SCL target volumes. Consequently, many radiation oncologists advocate for enlarging the SCL irradiation target volume to include both the medial and posterolateral SCL regions. Nevertheless, it remains uncertain whether adding the posterolateral SCL irradiation improves survival outcomes for high-risk breast cancer patients. METHODS: The SUCLANODE trial is an open-label, multicenter, randomized, phase 3 trial comparing the efficacy and adverse events of medial SCL irradiation (M-SCLI group) and medial plus posterolateral SCL irradiation (entire SCL irradiation, E-SCLI group) in high-risk breast cancer patients who underwent breast conserving-surgery or mastectomy. Patients with pathological N2-3b disease following initial surgery, or clinical stage III or pathological N1-3b if receiving neoadjuvant systemic therapy, are eligible and randomly assigned (1:1) to M-SCLI group and E-SCLI group. Stratification is by chemotherapy sequence (neoadjuvant vs. adjuvant), T stage (T3-4 vs. T1-2), N stage (N1-2 vs. N3), and ER status (positive vs. negative). Other radiation volumes are identical in the two arms, including breast/chest wall, undissected axillary lymph node, and internal mammary node. Advanced intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), or tomotherapy techniques are recommended. Both hypofractionated and conventional fractionation schedules are permitted. The primary end point is invasive disease-free survival, and secondary end points included overall survival, SCL recurrence, local-regional recurrence, distance recurrence, safety outcome, and patient-reported outcomes. The target sample size is 1650 participants. DISCUSSION: The results of the SUCLANODE trial will provide high-level evidence regarding whether adding posterolateral SCL irradiation to medial SCL target volume provides survival benefit in patients with high-risk breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05059379. Registered 28 September 2021, https://www. CLINICALTRIALS: gov/ct2/show/NCT05059379 .

Biological function and clinical application prospect of tsRNAs in digestive system biology and pathology.

tsRNAs are small non-coding RNAs originating from tRNA that play important roles in a variety of physiological activities such as RNA silencing, ribosome biogenesis, retrotransposition, and epigenetic inheritance, as well as involvement in cellular differentiation, proliferation, and apoptosis. tsRNA-related abnormalities have a significant influence on the onset, development, and progression of numerous human diseases, including malignant tumors through affecting the cell cycle and specific signaling molecules. This review introduced origins together with tsRNAs classification, providing a summary for regulatory mechanism and physiological function while dysfunctional effect of tsRNAs in digestive system diseases, focusing on the clinical prospects of tsRNAs for diagnostic and prognostic biomarkers. Video Abstract.

A tRF-5a fragment that regulates radiation resistance of colorectal cancer cells by targeting MKNK1.

Radiotherapy serves as a crucial strategy in the treatment of colorectal cancer (CRC). However, its efficacy is often hindered by the challenge of radiation resistance. Although the literature suggests that some tRNA-derived small RNAs (tsRNAs) are associated with various cancers, studies reporting the relationship of tsRNAs with cancer cell radiosensitivity have not been published yet. In our study, we utilized tsRNAs sequencing to predict differentially expressed tsRNAs in two CRC cells and their radioresistant cells, and 10 tsRNAs with significant differences in expression were validated by qPCR. The target genes of tRF-16-7X9PN5D were predicted and verified by the bioinformatics, dual-luciferase reporter gene assay and western blotting analyses. Wound healing, colony formation, transwell invasion and CCK-8 assays were performed to detect the effects of tRF-16-7X9PN5D on cell function and radiosensitivity. Western blotting evaluated the relationship between tRF-16-7X9PN5D and the MKNK-eIF4E axis. Our findings demonstrated that tRF-16-7X9PN5D expression was substantially downregulated in radioresistant CRC cells. Furthermore, tRF-16-7X9PN5D could promote CRC cells' ability to proliferate, migrate, invade and obtain radiation resistance by targeting MKNK1. Finally, tRF-16-7X9PN5D could regulate eIF4E phosphorylation via MKNK1. This investigation indicated that tRF-16-7X9PN5D has an essential regulatory role in the radiation resistance of CRC by directly targeting MKNK1, and may be a new pathway for regulating the CRC radiosensitivity.

In Situ Characterization of 17-4PH Stainless Steel by Small-Angle Neutron Scattering.

17-4PH martensitic steel is usually used as valve stems in nuclear power plants and it suffers from thermal aging embrittlement due to long-time service in a high-temperature and high-pressure environment. Here, we characterized the evolution of microstructures at the nano-scale in 17-4PH steel by in situ small-angle neutron scattering (SANS) with a thermo-mechanically coupled loading device. The device could set different temperatures and tensile so that an in situ SANS experiment could dynamically characterize the process of nanoscale structural changes. The results showed that with increasing thermal aging time, the ε-Cu phase precipitates and grows as the temperature is 475 °C and 590 °C, and the ε-Cu phase is spherical at 475 °C but became elongated cylinders at 590 °C. Moreover, the loading stress could aid in the growth of the ε-Cu phase at 475 °C.

Dysregulation of Transfer RNA-derived Small RNAs that Regulate Cell Activity and its Related Signaling Pathways in Human Cancers.

tsRNAs are small noncoding RNAs that originate from tRNA cleavage and play important regulatory roles in gene expression, translation, transcription, and epigenetic modification. The dysregulation of tsRNAs in cancer disrupts gene expression and perturbs various cellular activities, including cell proliferation, apoptosis, migration, and invasion. Moreover, tsRNAs may influence cancer development by regulating related cell signaling pathways. In this review, we first examine the origins and classification of tsRNAs and their effects on tumor cell activity. To highlight the latest research progress of tsRNAs and signaling pathways, we summarize the possible mechanisms of tsRNAs in specific tumor-related signaling pathways, including the Wnt, TGFb1, MAPK, PI3K-AKT, Notch, and MDM2/p53 signaling pathways, that have been identified in recent research.

Survival benefit of radiotherapy and nomogram for patients with primary tracheal malignant tumors: a propensity score-matched SEER database analysis.

PURPOSE: The purpose of this study was to conduct a matched-pair analysis to assess the impact of radiotherapy (RT) on patients with malignant tracheal tumors using the surveillance, epidemiology, and end results database. Additionally, a predictive nomogram was developed for patients with malignant tracheal tumors. METHODS: Propensity score matching (PSM) was used to minimize bias between the RT and no-RT groups. We utilized both univariate and multivariate Cox proportional hazards regression analyses to identify independent prognostic factors for patients and subgroups. We developed a novel nomogram and evaluated its results using the C-index. RESULTS: A total of 648 patients between 1975 and 2019 were included, and 160 patients in RT were 1:1 propensity score-matched with no-RT. The independent prognostic factors for patients with tracheal malignant tumors were surgery, marital status, disease extension, pathology, and age. The independent risk factors for patients without surgery included RT and disease extension. The C-index confirmed that the nomogram accurately predicted the prognosis of patients with tracheal malignant tumors. CONCLUSIONS: Our findings suggest that RT may provide a survival benefit for tracheal cancer patients who did not undergo surgery. The nomogram can be a useful tool for predicting prognosis in patients with tracheal malignant tumors.

Integrated Analysis of microRNA and RNA-Seq Reveals Phenolic Acid Secretion Metabolism in Continuous Cropping of Polygonatum odoratum.

Polygonatum odoratum (Mill.) Druce is an essential Chinese herb, but continuous cropping (CC) often results in a serious root rot disease, reducing the yield and quality. Phenolic acids, released through plant root exudation, are typical autotoxic substances that easily cause root rot in CC. To better understand the phenolic acid biosynthesis of P. odoratum roots in response to CC, this study performed a combined microRNA (miRNA)-seq and RNA-seq analysis. The phenolic acid contents of the first cropping (FC) soil and CC soil were determined by HPLC analysis. The results showed that CC soils contained significantly higher levels of p-coumaric acid, phenylacetate, and caffeic acid than FC soil, except for cinnamic acid and sinapic acid. Transcriptome identification and miRNA sequencing revealed 15,788 differentially expressed genes (DEGs) and 142 differentially expressed miRNAs (DEMs) in roots from FC and CC plants. Among them, 28 DEGs and eight DEMs were involved in phenolic acid biosynthesis. Meanwhile, comparative transcriptome and microRNA-seq analysis demonstrated that eight miRNAs corresponding to five target DEGs related to phenolic acid synthesis were screened. Among them, ath-miR172a, ath-miR172c, novel_130, sbi-miR172f, and tcc-miR172d contributed to phenylalanine synthesis. Osa-miR528-5p and mtr-miR2673a were key miRNAs that regulate syringyl lignin biosynthesis. Nta-miR156f was closely related to the shikimate pathway. These results indicated that the key DEGs and DEMs involved in phenolic acid anabolism might play vital roles in phenolic acid secretion from roots of P. odoratum under the CC system. As a result of the study, we may have a better understanding of phenolic acid biosynthesis during CC of roots of P. odoratum.

High eukaryotic initiation factor 5A2 expression predicts poor prognosis and may participate in the SNHG16/miR-10b-5p/EIF5A2 regulatory axis in head and neck squamous cell carcinoma.

BACKGROUND: This study attempted to investigate the significance of eukaryotic initiation factor 5A2 (EIF5A2) in the prognosis and regulatory network of head and neck squamous cell carcinoma (HNSCC). METHODS: EIF5A2 expression, prognostic information, and methylation levels of HNSCC were collected from the Cancer Genome Atlas (TCGA) database. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot analyses were performed to determine EIF5A2 levels in HNSCC and normal tissue samples. R software was employed for expression analysis and prognosis assessment of EIF5A2 in HNSCC. A competing endogenous RNA (ceRNA) network was generated with the starBase database. Gene set enrichment analysis (GSEA) was used to determine the enriched physiological functions and network related to high expression of EIF5A2 in HNSCC. Immune infiltration-related outcomes were acquired from the CIBERSORT and Tumor Immune Estimation Resource (TIMER) database. RESULTS: EIF5A2 overexpression was observed in HNSCC and linked to poor progression-free survival and overall survival time. Cox regression analyses showed that EIF5A2 level was a stand-alone indicator of HNSCC patients' prognosis. A ceRNA network analysis highlighted the SNHG16/miR-10b-5p/EIF5A2 axis in EIF5A2 regulation. The GSEA results indicated that EIF5A2 was involved in complex signaling pathways. The CIBERSORT and TIMER databases revealed significant associations between EIF5A2 expression and immune cell infiltration. CONCLUSION: EIF5A2 overexpression may be a risk factor for prognosis in HNSCC and may be regulated by the SNHG16/miR-10b-5p/EIF5A2 axis.

Establishment and validation of a redox-related long non-coding RNAs prognostic signature in head and neck squamous cell carcinoma.

Reduction and oxidation (redox) reactions occur in living organisms as part of normal cellular metabolism. Here, we established a novel redox-related long non-coding RNAs (rrlncRNAs) signature to predict the prognosis and therapeutic response in Head and neck squamous cell carcinoma (HNSCC). The expression profile and clinical information were obtained from the TCGA project. In total, 10 differently expressed rrlncRNAs associated with prognosis were identified and involved in a prognostic risk score signature by the least absolute shrinkage and selection operator penalized Cox analysis. The area under the receiver operating characteristic curves of the survival rates predicted by the rrlncRNAs signature over one, two, and three years were found to be 0.651, 0.670, and 0.679. Following the completion of the Kaplan-Meier survival study, we discovered that the lower-risk cohort exhibited a much longer overall survival period in contrast with the higher-risk cohort. Univariate and multivariable Cox regression analyses demonstrated that the risk score independently served as a significant predictive factor. GO annotation and KEGG pathway analyses illustrated that the rrlncRNAs signature was strongly associated with immune-related functions as well as signaling pathways. The tumor-infiltrating immune cells, tumor microenvironment, immune-related functions, HLA gene family expression, immune checkpoint genes expression, and somatic variants differed substantially between the low- and high-risk cohorts. Moreover, patients in low-risk group were predicted to present a favorable immunotherapy responsiveness, while in contrast, the high-risk group patients might have a stronger sensitivity to "docetaxel". According to our findings, the rrlncRNAs signature showed an excellent prognosis predictive value and might indicate therapeutic response to immunotherapy in HNSCC.

Bioinformatics algorithm for lung adenocarcinoma based on macropinocytosis-related long noncoding RNAs as a reliable indicator for predicting survival outcomes and selecting suitable anti-tumor drugs.

As a highly conserved endocytic mechanism during evolution, macropinocytosis is enhanced in several malignant tumors, which promotes tumor growth by ingesting extracellular nutrients. Recent research has emphasized the crucial role of macropinocytosis in tumor immunity. In the present study, we established a new macropinocytosis-related algorithm comprising molecular subtypes and a prognostic signature, in which patients with lung adenocarcinoma (LUAD) were classified into different clusters and risk groups based on the expression of 16 macropinocytosis-related long noncoding RNAs. According to the molecular subtypes, we discovered that patients with LUAD in cluster1 had a higher content of stromal cells and immune cells, stronger intensity of immune activities, higher expression of PD1, PDL1, and HAVCR2, and a higher tumor mutational burden, while patients in cluster2 exhibited better survival advantages. Furthermore, the constructed prognostic signature revealed that low-risk patients showed better survival outcomes, earlier tumor stage, higher abundance of stromal cells and immune cells, higher immune activities, higher expression of PD1, PDL1, CTLA4, and HAVCR2, and more sensitivity to Paclitaxel and Erlotinib. By contrast, patients with high scores were more suitable for Gefitinib treatment. In conclusion, the novel algorithm that divided patients with LUAD into different groups according to their clusters and risk groups, which could provide theoretical support for predicting their survival outcomes and selecting drugs for chemotherapy, targeted therapy, and immunotherapy.

Eukaryotic initiation factor 5A2 mediates hypoxia-induced autophagy and cisplatin resistance.

Hypoxia-induced cisplatin resistance is a major challenge during non-small cell lung cancer (NSCLC) treatment. Based on previous studies, we further explored the effect of eukaryotic initiation factor 5A2 (eIF5A2) in hypoxia-induced cisplatin resistance. In this study, we found that autophagy and cisplatin resistance were increased under hypoxic conditions in three different NSCLC cell lines. Compared with that under normoxic conditions, dramatic upregulation of eIF5A2 and hypoxia inducible factor 1 subunit alpha (HIF-1α) levels were detected under hypoxia exposure. Small interfering RNA silencing of HIF-1α resulted in decreased expression of eIF5A2, indicating that eIF5A2 acts downstream of HIF-1α. In addition, the expression of eIF5A2 was significantly higher in NSCLC tumors compared with that in normal tissues. RNA silencing-mediated downregulation of eIF5A2 decreased hypoxia-induced autophagy, thereby reducing hypoxia-induced cisplatin resistance in NSCLC cells. The roles of eIF5A2 in cisplatin resistance were further validated in vivo. Combined treatment using eIF5A2-targeted downregulation together with cisplatin significantly inhibited tumor growth compared with cisplatin alone in the subcutaneous mouse model. In conclusions, eIF5A2 overexpression is involved in hypoxia-induced autophagy during cisplatin resistance. We suggest that a combination of eIF5A2 targeted therapy and cisplatin chemotherapy is probably an effective strategy to reverse hypoxia-induced cisplatin resistance and inhibit NSCLC development.

Upregulation of INHBA mediated by the transcription factor BHLHE40 promotes colon cancer cell proliferation and migration.

BACKGROUND: Colon cancer is highly prevalent, and cell proliferation and migration are major reasons for its progression to malignancy. The upregulation of INHBA, a glycoprotein hormone that regulates the secretion of pituitary hormones, is documented to be oncogenic in numerous cancers, consisting of breast, gastric, and ovarian cancer. Herein, we assessed the role of INHBA in the proliferation along with the migration of colon cancer cells. METHODS: TCGA datasets were used to assess INHBA expression and its correlation with prognosis in colon cancer patients. Analyses on JASPAR, PROMO, and ENCODE databases, uncovered high correlation between INHBA and BHLHE40. Western blot and RT-qPCR analysis were used to determine protein and mRNA levels. Cell transfection inhibited the expression of INHBA and BHLHE40. Cell proliferation rates were determined using CCK8 analysis. Wound healing assays were adopted to explore cell migration. RESULTS: INHBA is markedly elevated in colon cancer tissues along with cells and is a predictive factor for patient's prognosis with colon cancer. INHBA silencing suppressed colon cancer cell proliferation and migration. Furthermore, we confirmed the association of INHBA with BHLHE40 in colon cancer cells. BHLHE40 could directly modulates INHBA expression. Here, we show that BHLHE40 modulates the expression of INHBA, which influences the proliferation, and migration of colon cancer cells. CONCLUSION: INHBA acts as an oncogene in colon cancer and it can be regulated by the transcription factor BHLHE40.

Construction of an algorithm based on oncosis-related LncRNAs comprising the molecular subtypes and a risk assessment model in lung adenocarcinoma.

BACKGROUND: As an important non-apoptotic cell death method, oncosis has been reported to be closely associated with tumors in recent years. However, few research reported the relationship between oncosis and lung cancer. METHODS: In this study, we established an oncosis-based algorithm comprised of cluster grouping and a risk assessment model to predict the survival outcomes and related tumor immunity of patients with lung adenocarcinomas (LUAD). We selected 11 oncosis-related lncRNAs associated with the prognosis (CARD8-AS1, LINC00941, LINC01137, LINC01116, AC010980.2, LINC00324, AL365203.2, AL606489.1, AC004687.1, HLA-DQB1-AS1, and AL590226.1) to divide the LUAD patients into different clusters and different risk groups. Compared with patients in clsuter1, patients in cluster2 had a survival advantage and had a relatively more active tumor immunity. Subsequently, we constructed a risk assessment model to distinguish between patients into different risk groups, in which low-risk patients tend to have a better prognosis. GO enrichment analysis revealed that the risk assessment model was closely related to immune activities. In addition, low-risk patients tended to have a higher content of immune cells and stromal cells in tumor microenvironment, higher expression of PD-1, CTLA-4, HAVCR2, and were more sensitive to immune checkpoint inhibitors (ICIs), including PD-1/CTLA-4 inhibitors. The risk score had a significantly positive correlation with tumor mutation burden (TMB). The survival curve of the novel oncosis-based algorithm suggested that low-risk patients in cluster2 have the most obvious survival advantage. CONCLUSION: The novel oncosis-based algorithm investigated the prognosis and the related tumor immunity of patients with LUAD, which could provide theoretical support for customized individual treatment for LUAD patients.

The prognostic effect of PNN in digestive tract cancers and its correlation with the tumor immune landscape in colon adenocarcinoma.

BACKGROUND: The present study investigated the expression, mutation, and methylation profile of PNN and its prognostic value in digestive tract cancers. The disparities in signaling pathways and the immune landscape in colon adenocarcinoma (COAD) based on PNN expression were specifically explored. METHODS: The expression, mutation, methylation levels of PNN, and survival data in esophageal cancer, gastric adenocarcinoma, COAD, and rectal adenocarcinoma were evaluated using several bioinformatic databases. Gene Ontology (GO) enrichment analysis and gene set enrichment analysis (GSEA) were performed to investigate the enriched biological functions and pathways in COAD. Several acknowledged bioinformatic algorithms were employed to assess the correlation between PNN expression and the tumor immune landscape in COAD. RESULTS: PNN was upregulated and remarkably related to tumor stage in digestive tract cancers. High expression of PNN was positively associated with poor progression-free survival and overall survival time, specifically in COAD. PNN expression was identified as an independent prognostic factor in COAD. GO and GSEA analyses revealed that PNN participates in multiple biological processes underlying carcinogenicity in COAD. Further investigation showed that PNN expression was significantly associated with tumor-infiltrating immune cells, immune cell functions, and several immune checkpoints in COAD. The PNN low expression group had a lower tumor immune dysfunction and exclusion (TIDE) score and a higher immunophenoscore (IPS), indicating a better response to immunotherapy. CONCLUSION: PNN was highly expressed in digestive tract cancers and could act as an independent prognostic factor and a response predictor for immunotherapy in COAD.

Identification of an Autophagy-Related lncRNA Prognostic Signature and Related Tumor Immunity Research in Lung Adenocarcinoma.

Autophagy is closely associated with the tumor immune microenvironment (TIME) and prognosis of patients with lung adenocarcinoma (LUAD). In the present study, we established a signature on the basis of long noncoding RNAs (lncRNAs) related to autophagy (ARlncRNAs) to investigate the TIME and survival of patients with LUAD. We selected ARlncRNAs associated with prognosis to construct a model and divided each sample into different groups on the basis of risk score. The ARlncRNA signature could be recognized as an independent prognostic factor for patients with LUAD, and patients in the low-risk group had a greater survival advantage. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis suggested that several immune functions and pathways were enriched in different groups. A high-risk score correlated significantly negatively with high abundance of immune cells and stromal cells around the tumor and high tumor mutational burden. Low-risk patients had a higher PD-1, CTLA-4, and HAVCR2 expression and had a better efficacy of immune checkpoint inhibitors, including PD-1/CTLA-4 inhibitor. A reliable signature on the basis of ARlncRNAs was constructed to explore the TIME and prognosis of patients with LUAD, which could provide valuable information for individualized LUAD treatment.

Establishment of a novel ferroptosis-related lncRNA pair prognostic model in colon adenocarcinoma.

Long non-coding RNAs (lncRNAs) have been reported to be prognostic factors for cancer. Ferroptosis is an iron-dependent process of programmed cell death. Here, we established a ferroptosis-related lncRNA (frlncRNA) pair signature and revealed its prognostic value in colon adenocarcinoma (COAD) by analyzing the data from The Cancer Genome Atlas (TCGA). FrlncRNAs were identified based on co-expression analysis using the Pearson correlation. Differentially expressed frlncRNAs (DEfrlncRNAs) were recognized and paired, followed by prognostic assessment using univariate Cox regression analysis. The least absolute shrinkage and selection operator (LASSO) penalized Cox analysis was used to determine and construct a risk score prognostic model, by which the receiver operating characteristic (ROC) curves for predicting the overall survival (OS) were conducted. Following the evaluation of whether it was an independent prognostic factor, correlations between the risk score model and clinicopathological characteristics, hypoxia- and immune-related factors, and somatic variants were investigated. In total, 148 DEfrlncRNA pairs were identified, 25 of which were involved in a risk score prognostic signature. The area under ROC curves (AUCs) representing the predictive effect for 1-, 3-, and 5-year survival rates were 0.860, 0.885, and 0.934, respectively. The risk score model was confirmed as an independent prognostic factor and was significantly superior to the clinicopathological characteristics. Correlation analyses showed disparities in clinicopathological characteristics, hypoxia- and immune-related factors, and somatic variants, as well as specific signaling pathways between high- and low-risk groups. The novel risk score prognostic model constructed by pairing DEfrlncRNAs showed promising clinical prediction value in COAD.

Construction of an immune-related lncRNA signature as a novel prognosis biomarker for LUAD.

The tumor immune microenvironment of lung cancer is associated with prognosis and immunotherapy efficacy. Long noncoding RNAs are identified as prognostic biomarkers associated with immune functions. We constructed a signature comprising differentially expressed immune-related lncRNAs to predict the prognosis of patients with lung adenocarcinoma. We established the immune-related lncRNA signature by pairing immune-related lncRNAs regardless of expression level and lung adenocarcinoma patients were divided into high- and low-risk groups. The prognosis of patients in the two groups was significantly different; The immune-related lncRNA signature could serve as an independent lung adenocarcinoma prognostic indicator. The signature correlated negatively with B cell, CD4+ T cell, M2 macrophage, neutrophil, and monocyte immune infiltration. Patients with low risk scores had a higher abundance of immune cells and stromal cells around the tumor. Gene set enrichment analysis showed that samples from low-risk group were more active in the IgA production in intestinal immune network and the T and B cell receptor signaling pathway. High-risk groups had significant involvement of the cell cycle, DNA replication, adherens junction, actin cytoskeleton regulation, pathways in cancer, and TGF-ß signaling pathways. High risk scores correlated significantly negatively with high CTLA-4 and HAVCR2 expression and higher median inhibitory concentration of common anti-tumor chemotherapeutics (e.g., cisplatin, paclitaxel, gemcitabine) and targeted therapy (e.g., erlotinib and gefitinib). We identified a reliable immune-related lncRNA lung adenocarcinoma prognosis model, and the immune-related lncRNA signature showed promising clinical prediction value.

Expression mode and prognostic value of FXYD family members in colon cancer.

The FXYD gene family comprises seven members that encode a class of small-membrane proteins characterized by an FXYD motif and interact with Na+/K+-ATPase. Until now, the expression patterns and prognostic roles of the FXYD family in colon cancer (CC) have not been systematically reported. Gene expression, methylation, clinicopathological features and the prognoses of CC patients were obtained from The Cancer Genome Atlas (TCGA) database. The expression feature and prognostic values of FXYD members were identified. Gene set enrichment analysis (GSEA) was performed to explore the potential mechanism underlying the function of the FXYD family in CC. Tumor Immune Estimation Resource (TIMER) and CIBERSORT analysis were used to assess the correlations between FXYD family members and tumor immune infiltrating cells (TIICs). FXYD family members were differentially expressed in CC except for FXYD2. FXYD2, FXYD3 and FXYD4 were revealed as independent prognostic factors for recurrence, while FXYD3 and FXYD7 were identified as prognostic factors for survival according to univariate and multivariate analyses with Cox regression. GSEA revealed that FXYD family members were involved in complicated biological functions underlying cancer progression. TIMER and CIBERSORT analyses showed significant associations between FXYD family genes and TIICs. The present study comprehensively revealed the expression mode and prognostic value of FXYD members in CC, providing insights for further study of the FXYD family as potential clinical biomarkers in CC.