Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8+T cells in hepatocellular carcinoma using Multiplex Quantitative Analysis

Guo, Mengzhou; Yuan, Feifei; Qi, Feng; Sun, Jialei; Rao, Qianwen; Zhao, Zhiying; Huang, Peixin; Fang, Tingting; Yang, Biwei; jinglin, xia

doi:10.21203/rs.3.rs-19039/v1

Cited by 3 publications

(2 citation statements)

References 41 publications

(47 reference statements)

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“…[46] It is thought that positive expression of PD-L1 in tumors is an indicator of patients who are more likely to respond to treatment. [47] However, some patients who test positive for PD-L1 may not respond to treatment; more importantly, some patients who test negative may still respond, making this an imperfect biomarker. [48] A number of studies have reported con icting data on the relationship between PD-L1 expression and survival/poor prognosis in TETs.…”

Section: Discussionmentioning

confidence: 99%

Characteristics of Genomic Mutations and Signaling Pathway Alterations in Thymic Epithelial Tumors

Yang

Chen

Cheng

et al. 2021

Preprint

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Purpose: To elucidate mechanisms of thymic epithelial tumor (TET) canceration through characterization of genomic mutations and signal pathway alterations.Methods: Primary tumor and blood samples were collected from 21 patients diagnosed with TETs (thymoma and thymic cancer), 15 of whom were screened by nucleic acid extraction and total exon sequencing. Bioinformatics was used to comprehensively analyze sequencing data for these samples, including differences in tumor mutation burden (TMB) and signaling pathways.Results: We found that the gene with the highest mutation frequency in thymic carcinoma was ZNF429 (36%). In addition, mutations in BAP1 (14%), ABI1 (7%), BCL9L (7%), CHEK2 (7%) were only detected in thymic carcinoma, whereas ZNF721 mutations (7%) were found only in thymoma. Mean TMB values for thymic carcinoma and thymoma groups were 0.722 and 0.663 mutations per megabase (Mb), respectively, differences that were not statistically significant. There were significant differences in enriched pathways for cellular components between tumor metastasis and non-metastatic samples. The ErbB signaling pathway was enriched in both the thymoma group and the intersection group, whereas “pathways in cancer” was found in both the thymoma group and thymic cancer group. In contrast, enrichment of longevity-regulating and MAPK signaling pathways was found only in the thymoma group.Conclusions: We identified multiple differences in somatic genes and pathways, providing insights into differences between thymoma and thymic carcinoma that could aid in designing personalized clinical therapy.

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Section: Discussionmentioning

confidence: 99%

Characteristics of Genomic Mutations and Signaling Pathway Alterations in Thymic Epithelial Tumors

Yang

Chen

Cheng

et al. 2021

Preprint

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“…Advantages include (1) a fully automated staining process for medium throughput, (2) visualization of several markers on the same tissue section, and (3) signal amplification. This permits identification of cellular phenotypes in the context of a specific tissue compartment such as the tumor microenvironment [2–4]. Prior to routine implementation, these technologies require stringent validation of the antibody panel including staining order, marker co‐localization, antibody elution, spectral overlap, antibody cross‐reactivity, and decreased signal due to the potential of steric hindrance [1].…”

Section: Tyramide Signal Amplification (Tsa)mentioning

confidence: 99%

Clinical and research applications of multiplexed immunohistochemistry and in situ hybridization

McGinnis¹,

Ibarra-Lopez²,

Rost³

et al. 2021

The Journal of Pathology

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Over the past decade, invention and adoption of novel multiplexing technologies for tissues have made increasing impacts in basic and translational research and, to a lesser degree, clinical medicine. Platforms capable of highly multiplexed immunohistochemistry or in situ RNA measurements promise evaluation of protein or RNA targets at levels of plex and sensitivity logs above traditional methods – all with preservation of spatial context. These methods promise objective biomarker quantification, markedly increased sensitivity, and single‐cell resolution. Increasingly, development of novel technologies is enabling multi‐omic interrogations with spatial correlation of RNA and protein expression profiles in the same sample. Such sophisticated methods will provide unprecedented insights into tissue biology, biomarker science, and, ultimately, patient health. However, this sophistication comes at significant cost, requiring extensive time, practical knowledge, and resources to implement. This review will describe the technical features, advantages, and limitations of currently available multiplexed immunohistochemistry and spatial transcriptomic platforms. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Lymphocyte-activation gene 3 protein expression in tumor-infiltrating lymphocytes is associated with a poor prognosis of ovarian clear cell carcinoma

et al. 2023

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Background Histological analysis has revealed the need for new treatment techniques for epithelial ovarian cancer. Immune checkpoint inhibitors may be a new therapeutic strategy for ovarian clear cell carcinoma (OCCC). Lymphocyte-activation gene 3 (LAG-3), an immune checkpoint, is a poor prognostic factor and a new therapeutic target for several malignancies. In this study, we demonstrated the correlation between LAG-3 expression and the clinicopathological features of OCCC. We evaluated LAG-3 expression in tumor-infiltrating lymphocytes (TILs) via immunohistochemical analysis using tissue microarrays containing surgically resected specimens from 171 patients with OCCC. Results The number of LAG-3-positive cases was 48 (28.1%), whereas the number of LAG-3-negative cases was 123 (71.9%). LAG-3 expression significantly increased in patients with advanced stages (P = 0.036) and recurrence (P = 0.012); however, its expression did not correlate with age (P = 0.613), residual tumor (P = 0.156), or death (P = 0.086). Using the Kaplan − Meier method, LAG-3 expression was found to be correlated with poor overall survival (P = 0.020) and progression-free survival (P = 0.019). Multivariate analysis revealed LAG-3 expression (hazard ratio [HR] = 1.86; 95% confidence interval [CI], 1.00 − 3.44, P = 0.049) and residual tumor (HR = 9.71; 95% CI, 5.13 − 18.52, P < 0.001) as independent prognostic factors. Conclusion Our study demonstrated that LAG-3 expression in patients with OCCC may be a useful biomarker for the prognosis of OCCC and could serve as a new therapeutic target.

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Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8+T cells in hepatocellular carcinoma using Multiplex Quantitative Analysis

Cited by 3 publications

References 41 publications

Characteristics of Genomic Mutations and Signaling Pathway Alterations in Thymic Epithelial Tumors

Characteristics of Genomic Mutations and Signaling Pathway Alterations in Thymic Epithelial Tumors

Clinical and research applications of multiplexed immunohistochemistry and in situ hybridization

Lymphocyte-activation gene 3 protein expression in tumor-infiltrating lymphocytes is associated with a poor prognosis of ovarian clear cell carcinoma

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