Application and Innovation of Multiomics Technologies in Clinical Oncology

Editorial

28 March 2023

Editorial: Application and innovation of multiomics technologies in clinical oncology

Xinmin Li

Anton Budzin

and

Ye Wang

896 views

1 citations

Editors

Ye Wang

Qingdao University, The Affiliated Qingdao Central Hospital of Qingdao University

Xiaoming Xing

The Affiliated Hospital of Qingdao University

Xinmin Li

University of California, Los Angeles

Anton A. Buzdin

European Organisation for Research and Treatment of Cancer

Impact

Original Research

23 March 2023

Heterogeneous pattern of gene expression driven by TTN mutation is involved in the construction of a prognosis model of lung squamous cell carcinoma

Zhao Liu

, 6 more and

Chunlin Zhang

1,924 views

2 citations

Epigenetics is influenced by chromatin stretching, nuclear deformation leads to genome instability and stress affects both transcription and protein production.

Review

17 March 2023

The role of physics in multiomics and cancer evolution

Lucie E. Gourmet

and

Simon Walker-Samuel

2,880 views

2 citations

(A): PARM1 expression distribution and survival distribution of osteosarcoma patients; (B): PARM1 high and low expression survival curve; (C): ROC curves of 1 year, 3 years and 5 years.

Original Research

06 March 2023

The bioinformatic approach identifies PARM1 as a new potential prognostic factor in osteosarcoma

Haijun Feng

, 2 more and

Shengbao Wang

2,900 views

1 citations

The forest plot shows PRICKLE1 as a prognosis-related Wnt signaling pathway gene.

Original Research

13 February 2023

Wnt signaling pathway-related gene PRICKLE1 is a prognostic biomarker for esophageal squamous cell carcinoma

Jinxian He

, 6 more and

Weiyu Shen

1,871 views

1 citations

Original Research

16 January 2023

LASSO-based screening for potential prognostic biomarkers associated with glioblastoma

Yin Tian

, 1 more and

Yun Jiang

3,350 views

3 citations

Original Research

14 December 2022

Analysis of the regulatory mechanisms of prognostic immune factors in thyroid cancer

Yin Tian

, 1 more and

Xue Sun

2,563 views

2 citations

(A)The waterfall plot of tumor somatic mutation established based on the SP-LUAD (left) and MP-LUAD (right) cohort. (B, C, E) The difference of mutation frequency of common mutated genes between SP- and MP-LUAD lesions. (D) Six genes statistically different mutated among these two cohorts, including RBM10, CDK4, ATRX, NTRK1, PREX2, SS18. (F, G) Mutation Frequency of SP- and MP-LUAD lesions. * p<0.05.

Original Research

02 December 2022

Distinct gene mutation profiles among multiple and single primary lung adenocarcinoma

Yadong Wang

, 6 more and

Jiajun Du

With the development of technologies, multiple primary lung cancer (MPLC) has been detected more frequently. Although large-scale genomics studies have made significant progress, the aberrant gene mutation in MPLC is largely unclear. In this study, 141 and 44 lesions from single and multiple primary lung adenocarcinoma (SP- and MP-LUAD) were analyzed. DNA and RNA were extracted from formalin-fixed, paraffin-embedded tumor tissue and sequenced by using the next-generation sequencing-based YuanSu450TM gene panel. We systematically analyzed the clinical features and gene mutations of these lesions, and found that there were six genes differently mutated in MP-LUAD and SP-LUAD lesions, including RBM10, CDK4, ATRX, NTRK1, PREX2, SS18. Data from the cBioPortal database indicated that mutation of these genes was related to some clinical characteristics, such as TMB, tumor type, et al. Besides, heterogeneity analysis suggested that different lesions could be tracked back to monophyletic relationships. We compared the mutation landscape of MP-LUAD and SP-LUAD and identified six differentially mutated genes (RBM10, CDK4, ATRX, NTRK1, PREX2, SS18), and certain SNV loci in TP53 and EGFR which might play key roles in lineage decomposition in multifocal samples. These findings may provide insight into personalized prognosis prediction and new therapies for MP-LUAD patients.

3,496 views

11 citations

Original Research

14 December 2022

Identification of prognosis-related gene features in low-grade glioma based on ssGSEA

Yuanzhi He

, 1 more and

Sanyang Tan

2,229 views

5 citations

Original Research

22 November 2022

MIR4435-2HG in exosomes promotes gastric carcinogenesis by inducing M2 polarization in macrophages

Chaofeng Li

, 8 more and

Tao Fu

Gastric cancer (GC) is a cancer with a high mortality rate. lncRNAs play a role in regulating GC tumorigenesis. In this paper, we analyzed differentially expressed lncRNAs between GC and adjacent normal tissues using multiple bioinformatics tools to identify new potential targets in GC. Cell viability and migration ability were detected using the Cell Counting Kit-8 (CCK-8) and transwell assays, MIR4435-2HG was negatively correlated with the survival rate of GC patients, and by inhibiting the activity of MIR4435-2HG, the viability and migration ability of GC cells could be reduced. In addition, RT- qPCR and western blot to detect gene and protein level expression, transmission electron microscopy and nanoparticle tracking analysis (NTA) to study the efficiency of exosome isolation, and flow cytometry to observe cell differentiation were employed, delivery of MIR4435-2HG shRNA via MKN45 cell-derived exosomes significantly reversed the MKN45 exosome-induced M2 polarization in macrophages. Furthermore, the low expression of MIR4435-2HG in MKN45 cell-derived exosomes inhibited the Jagged1/Notch and JAK1/STAT3 pathways in macrophages; MIR4435-2HG downregulated exosomes were found to significantly inhibit GC tumor growth in vivo by establishing a mouse model. In short, MKN45 cell-derived exosomes deliver lncRNA MIR4435-2HG, which promotes gastric carcinogenesis by inducing macrophage M2 polarization.

2,413 views

18 citations

(A, B) Differential expression of necroptosis-related genes between the C1 and C3 subgroups. (C) Results of the whole genome survival analysis of cutaneous melanoma showing the top 20 genes. (D) Venn diagram. *p<0.05,**p<0.01, ***p<0.001.

Original Research

29 November 2022

PGAM5: A necroptosis gene associated with poor tumor prognosis that promotes cutaneous melanoma progression

Jianzhong Peng

, 3 more and

Peng Xiao

2,147 views

9 citations

Original Research

21 September 2022

DIRAS3, GPR171 and RAC2 were identified as the key molecular patterns associated with brain metastasis of breast cancer

Ji Dai

, 4 more and

Meidi Yan

Objective: Brain metastasis is a primary cause of morbidity and mortality in breast cancer patients. Therefore, elucidation and understanding of the underlying mechanisms are essential for the development of new therapeutic strategies.

Methods: Differential gene analysis was performed for those with and without distant metastasis in The Cancer Genome Atlas (TCGA) database and those with and without recurrence in the brain in the dataset GSE12276. The differentially expressed genes procured from the two databases were intersected to obtain the intersecting genes associated with brain metastasis. Thereafter, the intersecting genes were subjected to LASSO model construction to screen for prognostic genes. The expression of the obtained genes in metastatic breast cancer was observed, and survival analysis was performed. Finally, GSEA analysis of the obtained genes was performed, and the relationship between them and immune cells was explored.

Results: A total of 335 differential genes for the occurrence of distant metastases were obtained based on the TCGA database. A total of 1070 differential genes for recurrence to the brain were obtained based on the dataset GSE12276. The Venn diagram showed 24 intersecting genes associated with brain metastasis. The LASSO prognostic model contained a total of five genes (GBP2, GPR171, DIRAS3, RAC2, and CACNA1D). Expression difference analysis showed that GBP2, GPR171, DIRAS3, and RAC2 were significantly down-regulated in expression in metastatic breast cancer compared with primary breast cancer tumors. Only GPR171, DIRAS3, and RAC2 were strongly correlated with the overall survival of breast cancer patients. Their correlation analysis with immune cells showed that the correlation coefficient between the expression levels of DIRAS3 and immune cells was low, and the expression levels of GPR171 and RAC2 were more closely correlated with B cells and macrophages.

Conclusions: The expression of DIRAS3, GPR171 and RAC2, genes associated with brain metastasis, was reduced in metastatic breast cancer, and GPR171 was found to promote brain metastasis of breast cancer cells by inducing B cells and thereby.

3,536 views

9 citations

(A): one-way Cox regression analysis of the prognosis of 7 energy metabolism-related genes in pancreatic cancer; (B): expression differences between cancer and paracancer in TCGA; (C): expression differences between cancer and paracancer in GSE62165; (D–H): expression differences of genes in different age stages, grade stage, T stage, N stage, and pTNM stage in TCGA, respectively. *p<0.05, **p<0.01, ***p<0.001 compared with the control group. ns, no significant.

Original Research

29 September 2022

Prognostic signature construction of energy metabolism-related genes in pancreatic cancer

Hao Liu

, 6 more and

Yuxiang Zhao

2,193 views

4 citations

Original Research

12 September 2022

Single-cell transcriptome analysis reveals T-cell exhaustion in denosumab-treated giant cell tumor of bone

Meiling Yang

, 4 more and

Changye Zou

Denosumab (DMAB), a human monoclonal antibody against the receptor activator of the nuclear factor-kappa B ligand, is used for the treatment for unresectable giant cell tumor of bone (GCTB). However, little is known about the molecular and functional characteristics of GCTB-infiltrating lymphocytes after DMAB treatment. Here, we performed single-cell RNA sequencing and immunostaining assays to delineate the immune landscape of GCTB in the presence and absence of DMAB. We found that exhausted CD8⁺ T cells were preferentially enriched in DMAB-treated GCTB. A distinct M2-skewed type of tumor-associated macrophages (TAMs) comprises the majority of GCTB TAMs. We identified cytokines, including interleukin-10, and inhibitory receptors of M2 TAMs as important mediators of CD8⁺ T cell exhaustion. We further revealed that DMAB treatment notably increased the expression levels of periostin (POSTN) in GCTB cells. Furthermore, POSTN expression was transcriptionally regulated by c-FOS signaling and correlated with GCTB recurrence in patients after DMAB treatment. Collectively, our findings reveal that CD8⁺ T-cells undergo unappreciated exhaustion during DMAB therapy and that GCTB cell-derived POSTN educates TAMs and establishes a microenvironmental niche that facilitates GCTB recurrence.

6,519 views

6 citations

Original Research

15 September 2022

lncRNA NEAT1 promotes the proliferation and metastasis of hepatocellular carcinoma by regulating the FOXP3/PKM2 axis

Junping Pan

, 3 more and

Xinhua Zhu

2,355 views

10 citations

Original Research

02 September 2022

HOXA1 is a radioresistance marker in multiple cancer types

Lu He

, 3 more and

Yi Yu

(A) Representative immunohistochemistry images showing low and high HOXA1 expression in NPC tissues. Scale bars, 50 μm. (B) Overall survival curves of NPC patients. (C) Cumulative bar chart showing that high HOXA1 expression was correlated with high risk of local relapse in NPC patients. (D) knockdown of HOXA1 expression downregulated EGFR, CAV1 and CDK6 expression in CNE1 cells. (E) knockdown of HOXA1 expression reduced the proliferation of CNE1 cells. (F) knockdown of HOXA1 expression downregulated EGFR, CAV1 and CDK6 expression in HNE1 cells. (G) knockdown of HOXA1 expression reduced the proliferation of HNE1 cells. (H, I) Dose-survival curves showing that knockdown of HOXA1 expression enhanced the radiosensitivity of CNE1 and HNE1 NPC cells. **P < 0.01; ***P < 0.001.

Radiotherapy is an important therapeutic method for patients with cancer. However, radioresistance can cause treatment failure. Thus, there is an urgent need to investigate mechanisms of radioresistance and identity markers that could be used to predict radioresistance and prognosis of post-radiotherapy cancer patients. In the present study, we propose HOXA1 as a candidate biomarker of intrinsic radioresistance in multiple cancer types. By analyzing data from The Cancer Genome Atlas (TCGA), we found that HOXA1 was aberrantly upregulated in multiple cancers, and that elevated HOXA1 was significantly associated with poor prognosis of post-radiotherapy head and neck squamous cell carcinoma (HNSCC) and low-grade glioma (LGG) patients. Correlation analysis showed that HOXA1 expression was positively correlated with expression of EGFR, CDK6, and CAV1, which have been reported to enhance radioresistance. In addition, gene set enrichment analysis (GSEA) showed that the oxidative phosphorylation gene set was negatively enriched in HOXA1 high-expression samples in both HNSCC and LGG. Moreover, immunohistochemical assays indicated that high HOXA1 expression was significantly correlated with a high recurrence rate of nasopharyngeal carcinoma (NPC) after radiotherapy. Further in vitro experiments demonstrated that HOXA1 knockdown markedly attenuated the DNA repair capacity of NPC cells and sensibilized NPC cells to irradiation. Taken together, the results of this study demonstrate that HOXA1 has potential to be a predictive marker for radioresistance and post-radiotherapy prognosis that could help to guide individualized treatment in multiple cancer types.

3,390 views

5 citations

Original Research

01 September 2022

Comprehensive prognostic and immunological analysis of CCT2 in pan-cancer

Wenming Lv

, 2 more and

Shengbao Wang

3,061 views

4 citations

Original Research

16 August 2022

The prognostic value of immune-related genes AZGP1, SLCO5A1, and CTF1 in Uveal melanoma

Wanpeng Wang

and

Sha Wang

Objective: Uveal melanoma (UM) is an aggressive malignancy with a poor prognosis and no available effective treatment. Therefore, exploring a potential prognostic marker for UM could provide new possibilities for early detection, recurrence, and treatment.

Methods: In this study, we used “ConsensusClusterPlus” to classify patients with UM into subgroups, screened for significant differences in immune prognostic factors between subgroups, selected three genes using LASSO (Least absolute shrinkage and selection operator) regression to construct a risk model, and performed tumor immune cell infiltration analysis on the risk model. infiltration analysis, and then verified the heterogeneous role of the 3 core genes in other cancers by pan-cancer analysis and validate its expression by RT-qPCR in normal and tumor cells.

Results: We consistently categorized 80 UM patients into two subgroups after the immunogenetic set, where the UM1 subgroup had a better prognosis than the UM2 subgroup, and used 3 immune-related genes AZGP1, SLCO5A1, and CTF1 to derive risk scores as independent prognostic markers and predictors of UM clinicopathological features. We found significant differences in overall survival (OS) between low- and high-risk groups, and prognostic models were negatively correlated with B cell and myeloid dendritic cell and positively correlated with CD8+ T cell AZGP1 and CTF1 were significantly upregulated in UM cells compared with normal UM cells.

Conclusion: Immunogens are significantly associated with the prognosis of UM, and further classification based on genetic characteristics may help to develop immunotherapeutic strategies and provide new approaches to develop customized treatment strategies for patients.

2,545 views

6 citations

Original Research

09 August 2022

The global change of gene expression pattern caused by PTEN mutation affects the prognosis of glioblastoma

Shengjun Zhou

, 3 more and

Zhiqing Lin

2,557 views

4 citations

(A) Spearman correlation analysis of eight candidate genes in the TCGA-LIHC cohort. (B) Eight risk genes expression in paired tissues from TCGA database. (C) The ROC curve of independent risk genes in TCGA-LIHC cohort. (D) The mRNA levels of quantified using qRT-PCR analysis in human liver cell line and two HCC cell lines. (E) The protein expression of TTK, KIF2C, HAVCR1, and MMP1. (F) Immunohistochemistry of the HAVCR1 from the HPA database (*p < 0.05, **p < 0.01, ***p < 0.001).

Original Research

02 August 2022

Bioinformatics analysis and experimental verification of the prognostic and biological significance mediated by fatty acid metabolism related genes for hepatocellular carcinoma

Xiao-Ren Zhu

, 7 more and

Yi-Ping Du

Background: Liver cancer is among the leading causes of death related to cancer around the world. The most frequent type of human liver cancer is hepatocellular carcinoma (HCC). Fatty acid (FA) metabolism is an emerging hallmark that plays a promoting role in numerous malignancies. This study aimed to discover a FA metabolism-related risk signature and formulate a better model for HCC patients’ prognosis prediction.

Methods: We collected mRNA expression data and clinical parameters of patients with HCC using the TCGA databases, and the differential FA metabolism-related genes were explored. To create a risk prognostic model, we carried out the consensus clustering as well as univariate and multivariate Cox regression analyses. 16 genes were used to establish a prognostic model, which was then validated in the ICGC dataset. The accuracy of the model was performed using receiver operating characteristic (ROC) analyses, decision curve analysis (DCA) and nomogram. The immune cell infiltration level of risk genes was evaluated with single-sample GSEA (ssGSEA) algorithm. To reflect the response to immunotherapy, immunophenoscore (IPS) was obtained from TCGA-LIHC. Then, the expression of the candidate risk genes (p < 0.05) was validated by qRT-PCR, Western blotting and single-cell transcriptomics. Cellular function assays were performed to revealed the biological function of HAVCR1.

Results: According to the TCGA-LIHC cohort analysis, the majority of the FA metabolism-related genes were expressed differentially in the HCC and normal tissues. The prognosis of patients with high-risk scores was observed to be worse. Multivariate COX regression analysis confirmed that the model can be employed as an independent prognosis factor for HCC patients. Furthermore, ssGSEA analysis revealed a link between the model and the levels of immune cell infiltration. Our model scoring mechanism also provides a high predictive value in HCC patients receiving anti-PDL1 immunotherapy. One of the FA metabolism-related genes, HAVCR1, displays a significant differential expression between normal and HCC cell lines. Hepatocellular carcinoma cells (Huh7, and HepG2) proliferation, motility, and invasion were all remarkably inhibited by HAVCR1 siRNA.

Conclusion: Our study identified a novel FA metabolism-related prognostic model, revealing a better potential treatment and prevention strategy for HCC.

4,718 views

10 citations

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