SOX1 and PAX1 Are Hypermethylated in Cervical Adenocarcinoma and Associated with Better Prognosis

Background. The increased risk and poor survival outcome of cervical adenocarcinoma (CAC) demand for effective early diagnostic biomarkers that can predict the disease progression and outcome. The purpose of this study was to investigate the value of methylation status of SOX1 and PAX1 in the detection and prognosis of CAC. Methods. We performed a quantitative methylation-specific polymerase chain reaction in 205 cervical paraffin-embedded specimens (175 CACs, 30 noncancer cervical tissues). Overall and progression-free survival (OS and PFS, respectively) rates were calculated and compared using the Kaplan-Meier method. The prognostic value of SOX1m and PAX1m on CAC patients was assessed by the Cox regression model. A mathematical formula combining SOX1m, PAX1m, and age was constructed for survival prediction. Results. The methylation status of SOX1 and PAX1 was higher in CAC tissues than in noncancer cervical tissues. In addition, SOX1m-positive CAC patients showed a higher 5-year OS rate than SOX1m-negative patients. In CAC patients with smaller tumor size (<4 cm), the PAX1m-positive group showed a higher 5-year PFS rate than the PAX1m-negative group. In the algorithm combining SOX1m, PAX1m, and age, the low-risk group showed a better 5-year OS and PFS rate than the high-risk group. Conclusion. SOX1 and PAX1 methylation levels are higher in CAC than in normal cervical tissues and are potential biomarkers for monitoring CAC prognosis.

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Stemness-related LncRNA pair signature for predicting therapy response in gastric cancer

BMC Cancer ◽

10.1186/s12885-021-08798-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Quan Jiang ◽

Hao Chen ◽

Zhaoqing Tang ◽

Jie Sun ◽

Yuanyuan Ruan ◽

...

Keyword(s):

Gastric Cancer ◽

Cox Regression ◽

Risk Group ◽

Therapy Response ◽

Risk Groups ◽

High Risk Group ◽

Low Risk ◽

Survival Prediction ◽

Critical Feature ◽

Kaplan Meier

Abstract Objective As a critical feature of cancers, stemness is acknowledged as a contributor to the development of drug resistance in gastric cancer (GC). LncRNAs have been revealed to participate in this process. In this study, we tried to develop a stemness-related lncRNA pair signature as guidance for clinical decisions. Methods The analysis was initiated by collecting stemness-related lncRNAs in TCGA cohort. The differentially expressed stemness-related lncRNAs between normal and tumor tissues in GC patients from TCGA datasets were further collected to establish the signature based on Lasso and Cox regression analyses. The predictive efficacy of the signature for chemotherapy and immunotherapy was also tested. The practicality of this signature was also validated by Zhongshan cohort. Results A 13-DEsrlncRNA pair-based signature was established. The cutoff point acquired by the AIC algorithm divided the TCGA cohort into high and low risk groups. We found that the low-risk group presented with better survival (Kaplan-Meier analysis, p < 0.001). Cox regression analyse was also conducted to confirm the signature as an independent risk factor for GC {p < 0.001, HR = 1.300, 95% CI (1.231–1.373)]}. As for the practicality of this signature, the IC50 of cytotoxic chemotherapeutics was significantly higher in the high-risk group. The low-risk group also presented with higher immunophenoscore (IPS) in both the “CTLA4+ PD1+” (Mann-Whitney U test, p = 0.019) and “CTLA4- PD1+” (Mann-Whitney U test, p = 0.013) groups, indicating higher sensitivity to immunotherapy. The efficacy of the signature was also validated by Zhongshan cohort. Conclusions This study could not only provide a stemness-related lncRNA signature for survival prediction in GC patients but also established a model with predictive potentials for GC patients’ sensitivity to chemotherapy and immunotherapy.

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Exploration of a Novel Prognostic Risk Signature and Its Effect on the Immune Response in Nasopharyngeal Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.709931 ◽

2021 ◽

Vol 11 ◽

Author(s):

Shuang Zhao ◽

Xin Dong ◽

Xiaoguang Ni ◽

Lin Li ◽

Xin Lu ◽

...

Keyword(s):

Immune Response ◽

Nasopharyngeal Carcinoma ◽

Risk Group ◽

Progression Free Survival ◽

Gene Signature ◽

Metastatic Carcinoma ◽

High Risk Group ◽

Molecular Characteristics ◽

Novel Gene ◽

Kaplan Meier

Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic carcinoma with different molecular characteristics and clinical outcomes. In this work, we aimed to establish a novel gene signature that could predict the prognosis of NPC patients. A total of 13 significant genes between the recurrence/metastasis (RM) group and the no recurrence/metastasis (no-RM) group were identified by machine learning from RNA-Seq data including 60 NPC tumor biopsies. Based on these genes, a 4-mRNA signature (considering U2AF1L5, TMEM265, GLB1L and MLF1) was identified. Receiver operating characteristic (ROC) and Kaplan-Meier (K-M) analyses indicated that this signature had good prognostic value for NPC. The overall survival (OS) and progression-free survival (PFS) of the patients in the high-risk group were significantly shorter than those of the patients in the low-risk group (p = 0.00126 and p = 0.000059, respectively). The area under the ROC curve (AUC) values of the 4-mRNA signature were higher than those of T stage and N stage for OS (0.893 vs 0.619 and 0.582, respectively) and PFS (0.86 vs 0.538 and 0.622, respectively). Furthermore, the 4-mRNA signature was closely associated with cell proliferation and the immune response. The expression of GLB1L and TMEM265 was associated with the level of tumor-infiltrating immune cells (r > 0.4, p < 0.05). We have validated the model through measuring the expression levels of the 4-mRNA signature by qRT-PCR, in an independent cohort of NPC patients. Here, we report a novel gene signature that can serve as a new tool for predicting the prognosis of NPC patients.

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Identification of Novel Tumor Microenvironment-Related Long Non-coding RNAs to Predict the Prognosis for Hepatocellular Carcinoma

10.21203/rs.3.rs-877901/v1 ◽

2021 ◽

Author(s):

Shenglan Huang ◽

Jian Zhang ◽

Dan Li ◽

Xiaolan Lai ◽

Lingling Zhuang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

High Risk ◽

Tumor Microenvironment ◽

Cox Regression ◽

Risk Group ◽

High Risk Group ◽

Low Risk ◽

Clinicopathological Parameters ◽

Kaplan Meier ◽

The Impact

Abstract Introduction: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with poor prognosis. Tumor microenvironment (TME) plays a vital role in the tumor progression of HCC. Thus, we aimed to analyze the association of TME with HCC prognosis, and construct an TME-related lncRNAs signature for predicting the prognosis of HCC patients.Methods: We firstly assessed the stromal/immune /Estimate scores within the HCC microenvironment using the ESTIMATE algorithm based on TCGA database, and its associations with survival and clinicopathological parameters were also analyzed. Then, different expression lncRNAs were filtered out according to immune/stromal scores. Cox regression was performed to built an TME-related lncRNAs risk signature. Kaplan–Meier analysis was carried out to explored the prognostic values of the risk signature. Furthermore, we explored the biological functions and immune microenvironment feathers in high- and low risk groups. Lastly, we probed the association of the risk signature with the treatment responses to immune checkpoint inhibitors (ICIs) in HCC by comparing the immunophenoscore (IPS).Results: Stromal/immune /Estimate scores of HCC patients were obtained based on the ESTIMATE algorithm. The Kaplan-Meier curve analysis showed the high stromal/immune/ Estimate scores were significantly associated with better prognosis of the HCC patients. Then, six TME-related lncRNAs were screened for constructing the prognosis model. Kaplan-Meier survival curves suggested that HCC patients in high-risk group had worse prognosis than those with low-risk. ROC curve and Cox regression analyses demonstrated the signature could predict HCC survival exactly and independently. Function enrichment analysis revealed that some tumor- and immune-related pathways associated with HCC tumorigenesis and progression might be activated in high-risk group. We also discovered that some immune cells, which were beneficial to enhance immune responses towards cancer, were remarkably upregulated in low-risk group. Besides, there was closely correlation of immune checkmate inhibitors (ICIs) with the risk signature and the signature can be used to predict treatment response of ICIs.Conclusions: We analyzed the impact of the tumor microenvironment scores on the prognosis of patients with HCC. A novel TME-related prognostic risk signature was established, which may improve prognostic predictive accuracy and guide individualized immunotherapy for HCC patients.

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Prognostic utility of neutrophil-to-lymphocyte ratio in patients with metastatic colorectal cancer treated using different modalities

Current Oncology ◽

10.3747/co.27.6573 ◽

2020 ◽

Vol 27 (5) ◽

Author(s):

G. Nogueira-Costa ◽

I. Fernandes ◽

R. Gameiro ◽

J. Gramaça ◽

A.T. Xavier ◽

...

Keyword(s):

Colorectal Cancer ◽

High Risk ◽

Metastatic Colorectal Cancer ◽

Real World ◽

Cox Regression ◽

Risk Group ◽

High Risk Group ◽

Low Risk ◽

First Line ◽

Kaplan Meier

Introduction Inflammation is a critical component in carcinogenesis. The neutrophil-to-lymphocyte ratio (nlr) has been retrospectively studied as a biomarker of prognosis in metastatic colorectal cancer (mcrc). Compared with a low nlr, a high nlr is associated with worse prognosis. In the present study, we compared real-world survival for patients with mcrc based on their nlr group, and we assessed the utility of the nlr in determining first-line chemotherapy and metastasectomy benefit. Methods In this retrospective and descriptive analysis of patients with mcrc undergoing first-line chemotherapy in a single centre, the last systemic absolute neutrophil and lymphocyte count before treatment was used for the nlr. A receiver operating characteristic curve was used to estimate the nlr cut-off value, dividing the patients into low and high nlr groups. Median overall survival (mos) was compared using Kaplan–Meier curves and the log-rank test. A multivariate analysis was performed using a Cox regression model. Results The 102 analyzed patients had a median follow-up of 15 months. Regardless of systemic therapy, approximately 20% of patients underwent metastasectomy. The nlr cut-off was established at 2.35, placing 45 patients in the low-risk group (nlr < 2.35) and 57 in the high-risk group (nlr ≥ 2.35). The Kaplan–Meier analysis showed a mos of 39.1 months in the low-risk group and 14.4 months in the high-risk group (p < 0.001). Multivariate Cox regression on the nlr estimated a hazard ratio of 3.08 (p = 0.01). Survival analysis in each risk subgroup, considering the history of metastasectomy, was also performed. In the low-risk group, mos was longer for patients undergoing metastasectomy than for those not undergoing the procedure (95.2 months vs. 22.6 months, p = 0.05). In the high-risk group, mos was not statistically different for patients undergoing or not undergoing metastasectomy (24.3 months vs. 12.7 months, p = 0.08). Conclusions Our real-world data analysis of nlr in patients with mcrc confirmed that this biomarker is useful in predicting survival. It also suggests that nlr is an effective tool to choose first-line treatment and to predict the benefit of metastasectomy.

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A Glycolysis-Based Long Non-coding RNA Signature Accurately Predicts Prognosis in Renal Carcinoma Patients

Frontiers in Genetics ◽

10.3389/fgene.2021.638980 ◽

2021 ◽

Vol 12 ◽

Author(s):

Honghao Cao ◽

Hang Tong ◽

Junlong Zhu ◽

Chenchen Xie ◽

Zijia Qin ◽

...

Keyword(s):

Clinical Significance ◽

Risk Score ◽

Cox Regression ◽

Risk Group ◽

Enrichment Analysis ◽

Roc Curves ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Survival Prediction ◽

Kaplan Meier

BackgroundThe prognosis of renal cell carcinoma (RCC) varies greatly among different risk groups, and the traditional indicators have limited effect in the identification of risk grade in patients with RCC. The purpose of our study is to explore a glycolysis-based long non-coding RNAs (lncRNAs) signature and verify its potential clinical significance in prognostic prediction of RCC patients.MethodsIn this study, RNA data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate cox regression displayed six significantly related lncRNAs (AC124854.1, AC078778.1, EMX2OS, DLGAP1-AS2, AC084876.1, and AC026401.3) which were utilized in construction of risk score by a formula. The accuracy of risk score was verified by a series of statistical methods such as receiver operating characteristic (ROC) curves, nomogram and Kaplan-Meier curves. Its potential clinical significance was excavated by gene enrichment analysis.ResultsKaplan-Meier curves and ROC curves showed reliability of the risk score to predict the prognosis of RCC patients. Stratification analysis indicated that the risk score was independent predictor compare to other traditional clinical parameters. The clinical nomogram showed highly rigorous with index of 0.73 and precisely predicted 1-, 3-, and 5-year survival time of RCC patients. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene set enrichment analysis (GSEA) depicted the top ten correlated pathways in both high-risk group and low-risk group. There are 6 lncRNAs and 25 related mRNAs including 36 lncRNA-mRNA links in lncRNA-mRNA co-expression network.ConclusionThis research demonstrated that glycolysis-based lncRNAs possessed an important value in survival prediction of RCC patients, which would be a potential target for future treatment.

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Prognostic Significance of Severe Thrombocytopenia in Overall Survival of Patients with Myelodysplastic Syndromes Treated with Azacytidine. a Multicenter Study By the Hellenic MDS Study Group

Blood ◽

10.1182/blood-2018-99-119531 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1822-1822

Author(s):

Athanasios Galanopoulos ◽

Evdoxia Kamouza ◽

Christos K. Kontos ◽

Argiris Symeonidis ◽

Vassiliki Pappa ◽

...

Keyword(s):

Overall Survival ◽

Regression Analysis ◽

High Risk ◽

Myelodysplastic Syndromes ◽

Cox Regression ◽

Risk Group ◽

Prognostic Significance ◽

High Risk Group ◽

Severe Thrombocytopenia ◽

Kaplan Meier

Abstract INTRODUCTION: The hypomethylating agents 5-azacitidine (5-AZA) and decitabine are recently considered the most preferable treatment option for patients with intermediate-2 and high-risk myelodysplastic syndromes (MDS), by International Prognostic Scoring System (IPSS). 5-AZA responders experience improved survival both in clinical trials (AZA 001) and in the real-life setting. Thrombocytopenia is a common event in MDS, during the course of the disease; recently, severe thrombocytopenia (≤30,000 platelets/μL) has been suggested as an important factor regarding the survival of MDS patients. In the present study, we examined the potential prognostic significance of severe thrombocytopenia, in intermediate-2- and high-risk MDS patients, being treated with 5-AZA, during the first 3 years of treatment. METHODS: This retrospective study included 850 higher-risk patients (intermediate-2- and high-risk), registered in the the Hellenic MDS Registry, treated with 5-AZA from 2010 to 2018 and were followed up for a time period up to 3 years. Complete patient data were available for 225 patients. Biostatistical analysis performed in this study included Kaplan-Meier survival analysis and Cox regression. The level of statistical significance was set at a probability value of less than 0.050 (P<0.050). RESULTS: The current study included 225 patients (159 male and 66 women) with intermediate-2- or high-risk MDS treated with 5-AZA, with a median age of 74 years (range: 47 - 89). WHO diagnosis included 1 (0.4%) case of RCUD, 8 (3.6%) cases of RCMD, 3 (1.3%) cases of RCMD-RS, 43 (19.1%) cases of RAEB-1, and 170 (75.6%) cases of RAEB-2. According to IPSS, 174 (77.3%) patients were classified in the intermediate-2 risk group and 51 (22.7%) patients in the high-risk group. In addition, according to IPSS-R, 24 (10.7%) patients were categorized in the intermediate risk group, 106 (47.1%) patients in the high-risk group, and 95 (42.2%) patients in the very-high risk group. All patients were evaluated regarding response to 5-AZA treatment. The initial response at 6 months was: complete remission (CR) in 40 (18.4%) patients, partial remission (PR) in 24 (11.1%) patients, hematological improvement (HI) in 35 (16.1%) patients; therefore, the initial overall response rate (CR, PR, and HI) was 45.6%. Stable disease (SD) was achieved by 56 (25.8%) MDS patients, while 62 (28.5%) patients showed progression of disease (PD) or treatment failure. Severe thrombocytopenia was not predictive of response, as shown using logistic regression analysis. However, severe thrombocytopenia predicted poor overall survival (OS) in the first 3 years of treatment with 5-AZA, as shown by the Kaplan-Meier analysis (Figure 1; P=0.016). Regarding AML-free survival, a strong trend was observed for thy unfavorable prognostic role of this severe cytopenia (P=0.096). Univariate Cox regression analysis for OS revealed a statistically significant hazard ratio (HR) of 1.6 for MDS patients with severe thrombocytopenia (HR=1.6, 95% CI=1.08, P=0.019). CONCLUSIONS: Our study showed that severe thrombocytopenia (≤ 30,000 platelets/μL) in intermediate-2- and high-risk MDS patients, treated with 5-AZA, predicts lower OS rates during the first 3 years of treatment. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

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PLXDC1 May Serve As A Target For Combining Antiangiogenic Therapy and Immunotherapy In Gastric Adenocarcinoma

10.21203/rs.3.rs-816727/v1 ◽

2021 ◽

Author(s):

Xinwei Li ◽

Yonfei Fan ◽

Fang Su ◽

Zishu Wang

Keyword(s):

Risk Factor ◽

Cox Regression ◽

Risk Group ◽

Antiangiogenic Therapy ◽

High Risk Group ◽

The Cancer Genome Atlas ◽

Survival Prediction ◽

Antiangiogenic Agents ◽

Human Protein Atlas ◽

Cox Analysis

Abstract Introduction Based on the immunosuppression of traditional antiangiogenic agents in the treatment of tumors and the newly proposed concept of antiangiogenic therapy combined with immunotherapy, this paper will mainly explore the prospects of PLXDC1 in stomach adenocarcinoma (STAD) regarding antiangiogenic therapy and immunotherapy.Methods First, the transcriptional and translational levels of PLXDC1 in STAD were analyzed using the Oncomine, The Cancer Genome Atlas (TCGA) and Human Protein Atlas databases and then univariate and multivariate Cox regression analyses were performed using TCGA data. Next, we explored the correlation between PLXDC1 and STAD immunity from multiple aspects. Finally, based on the acquisition of immunomodulators associated with PLXDC1 expression from TISIDB, we constructed PLXDC1-related immune prognostic signatures of four genes (NT5E, CTLA, TGFBR1, and CSF1R) and constructed a nomogram for predicting survival to analyze the clinical utility of PLXDC1 in immunotherapy.Results Our results demonstrated that PLXDC1 was highly expressed in STAD and that its high expression was associated with poor prognosis in STAD. Multivariate Cox analysis suggested that PLXDC1 could be used as an independent prognostic risk factor for STAD. The high-risk group for which we constructed PLXDC1-related immune prognostic signatures showed poorer prognosis compared to low-risk group, and the risk score of our model could be used as an independent risk factor for STAD prognosis. Moreover, the nomogram survival prediction system showed good accuracy of the constructed immune signatures.Conclusions In conclusion, PLXDC1 can serve as a biomarker for the diagnosis and treatment of STAD and it may also be a new target for STAD immunotherapy. Therefore, PLXDC1 can combine antiangiogenic therapy with immunotherapy.

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Relating the gut metagenome and metatranscriptome to immunotherapy responses in melanoma patients

Genome Medicine ◽

10.1186/s13073-019-0672-4 ◽

2019 ◽

Vol 11 (1) ◽

Cited By ~ 9

Author(s):

Brandilyn A. Peters ◽

Melissa Wilson ◽

Una Moran ◽

Anna Pavlick ◽

Allison Izsak ◽

...

Keyword(s):

Microbial Community ◽

Gut Microbiota ◽

Cox Regression ◽

Risk Group ◽

Progression Free Survival ◽

High Risk Group ◽

Rrna Gene ◽

Nucleotide Biosynthesis ◽

Microbiome Composition ◽

Melanoma Patients

Abstract Background Recent evidence suggests that immunotherapy efficacy in melanoma is modulated by gut microbiota. Few studies have examined this phenomenon in humans, and none have incorporated metatranscriptomics, important for determining expression of metagenomic functions in the microbial community. Methods In melanoma patients undergoing immunotherapy, gut microbiome was characterized in pre-treatment stool using 16S rRNA gene and shotgun metagenome sequencing (n = 27). Transcriptional expression of metagenomic pathways was confirmed with metatranscriptome sequencing in a subset of 17. We examined associations of taxa and metagenomic pathways with progression-free survival (PFS) using 500 × 10-fold cross-validated elastic-net penalized Cox regression. Results Higher microbial community richness was associated with longer PFS in 16S and shotgun data (p < 0.05). Clustering based on overall microbiome composition divided patients into three groups with differing PFS; the low-risk group had 99% lower risk of progression than the high-risk group at any time during follow-up (p = 0.002). Among the species selected in regression, abundance of Bacteroides ovatus, Bacteroides dorei, Bacteroides massiliensis, Ruminococcus gnavus, and Blautia producta were related to shorter PFS, and Faecalibacterium prausnitzii, Coprococcus eutactus, Prevotella stercorea, Streptococcus sanguinis, Streptococcus anginosus, and Lachnospiraceae bacterium 3 1 46FAA to longer PFS. Metagenomic functions related to PFS that had correlated metatranscriptomic expression included risk-associated pathways of l-rhamnose degradation, guanosine nucleotide biosynthesis, and B vitamin biosynthesis. Conclusions This work adds to the growing evidence that gut microbiota are related to immunotherapy outcomes, and identifies, for the first time, transcriptionally expressed metagenomic pathways related to PFS. Further research is warranted on microbial therapeutic targets to improve immunotherapy outcomes.

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A Risk of Venous Thromboembolism Algorithm as a Predictor of Venous Thromboembolism in Patients with Colorectal Cancer

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/10760296211064900 ◽

2021 ◽

Vol 27 ◽

pp. 107602962110649

Author(s):

Ying Chen ◽

Yanchun Wang ◽

Suhong Xie ◽

Hui Zheng ◽

Ying Tong ◽

...

Keyword(s):

Colorectal Cancer ◽

Venous Thromboembolism ◽

Risk Group ◽

Progression Free Survival ◽

High Risk Group ◽

Cancer Center ◽

Free Survival ◽

Prognostic Analysis ◽

Increased Risk ◽

Patients Experience

Cancer patients experience an increased risk of venous thromboembolism (VTE). In this study, we investigated a risk of venous thromboembolism algorithm (RVTA) in patients with colorectal cancer and evaluated its ability to predict the prognosis of colorectal cancer. We retrospectively analyzed clinical data from 345 patients with colorectal cancer from January 2015 to December 2018 at the Shanghai Cancer Center to develop the RVTA. Additionally, the 345 patients were followed until December 2020 for prognostic analysis. The RVTA included the following variables: (a) platelet count, (b) blood transfusion history, (c) metastasis, (d) multiple chemotherapy regimens, and (e) the D-dimer level. Good predictive efficiency was observed for the RVTA (AUC was 0.825; 95% CI was 0.721 to 0.930). The median progression-free survival (PFS) of patients who had a score less than 4 (0-3), defined as the low-risk group, was significantly longer than that of the high-risk group, which included patients who had a score greater than 4 (4-8) (26 vs ten months, P < .001). The RVTA was a valuable predictor for VTE risk and had prognostic value in colorectal cancer.

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Immune-Related lncRNA Signature for Predicting the Immune Landscape of Head and Neck Squamous Cell Carcinoma

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.689224 ◽

2021 ◽

Vol 8 ◽

Author(s):

Ji Yin ◽

Xiaohui Li ◽

Caifeng Lv ◽

Xian He ◽

Xiaoqin Luo ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Regression Analysis ◽

High Risk ◽

Cell Carcinoma ◽

Cox Regression ◽

Risk Group ◽

Risk Groups ◽

High Risk Group ◽

Survival Prediction ◽

Cox Regression Analysis

Background: Long non-coding RNA (lncRNA) plays a significant role in the development, establishment, and progression of head and neck squamous cell carcinoma (HNSCC). This article aims to develop an immune-related lncRNA (irlncRNA) model, regardless of expression levels, for risk assessment and prognosis prediction in HNSCC patients.Methods: We obtained clinical data and corresponding full transcriptome expression of HNSCC patients from TCGA, downloaded GTF files to distinguish lncRNAs from Ensembl, discerned irlncRNAs based on co-expression analysis, distinguished differentially expressed irlncRNAs (DEirlncRNAs), and paired these DEirlncRNAs. Univariate Cox regression analysis, LASSO regression analysis, and stepwise multivariate Cox regression analysis were then performed to screen lncRNA pairs, calculate the risk coefficient, and establish a prognosis model. Finally, the predictive power of this model was validated through the AUC and the ROC curves, and the AIC values of each point on the five-year ROC curve were calculated to select the maximum inflection point, which was applied as a cut-off point to divide patients into low- or high-risk groups. Based on this methodology, we were able to more effectively differentiate between these groups in terms of survival, clinico-pathological characteristics, tumor immune infiltrating status, chemotherapeutics sensitivity, and immunosuppressive molecules.Results: A 13-irlncRNA-pair signature was built, and the ROC analysis demonstrated high sensitivity and specificity of this signature for survival prediction. The Kaplan–Meier analysis indicated that the high-risk group had a significantly shorter survival rate than the low-risk group, and the chi-squared test certified that the signature was highly related to survival status, clinical stage, T stage, and N stage. Additionally, the signature was further proven to be an independent prognostic risk factor via the Cox regression analyses, and immune infiltrating analyses showed that the high-risk group had significant negative relationships with various immune infiltrations. Finally, the chemotherapeutics sensitivity and the expression level of molecular markers were also significantly different between high- and low-risk groups.Conclusion: The signature established by paring irlncRNAs, with regard to specific expression levels, can be utilized for survival prediction and to guide clinical therapy in HNSCC.

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