Insights into E-Cadherin Impairment in CDH1-Unaltered Invasive Lobular Carcinoma: A Comprehensive Bioinformatic Study
Abstract
:1. Introduction
2. Results
2.1. Clinicopathological Features, Intrinsic Subtype, and Tumor Mutational Burden of CDH1-Altered and -Unaltered ILC
2.2. Genomic Landscape of Somatic Mutations and Comparison of Somatic Mutations and Amplification between CDH1-Altered and -Unaltered ILC
2.3. Identification of Differences in CDH1 mRNA, Protein, Methylation, and miRNA (hsa-mir-676) Levels between CDH1-Mutant and Non-Mutant Groups Using LinkedOmics
2.4. Gene Set Enrichment Analysis (GSEA) of Gene Ontology Annotations
3. Discussion
4. Materials and Methods
4.1. Data Collection of CDH1-Altered and -Unaltered ILC
4.2. Comparison of Clinicopathological Features and Molecular Subtypes between CDH1-Altered and -Unaltered ILC
4.3. TMB Estimation
4.4. CDH1 Alteration Analysis and Comparison of Mutation and Amplification Frequency of CDH1-Related Genes between CDH1-Altered and -Unaltered ILC
4.5. LinkedOmics Analysis
4.6. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Alteration Type | TCGA (n = 110) | METABRIC (n = 91) | Total (n = 201) |
---|---|---|---|
Mutation | |||
Missense, n (%) | 4 (3.6) | 9 (9.9) | 13 (6.5) |
In-frame, n (%) | 4 (3.6) | 1 (1.1) | 5 (2.5) |
Splice, n (%) | 11 (10.0) | 12 (13.2) | 23 (11.4) |
Truncating, n (%) | 82 (74.5) | 65 (71.4) | 147 (73.1) |
Homozygous deletion and mutation, n (%) | 3 (2.7) | 1 (1.1) | 4 (2.0) |
Homozygous deletion, n (%) | 4 (3.6) | 3 (3.3) | 7 (3.5) |
Structural variant, n (%) | 2 (1.8) | 0 (0) | 2 (1.0) |
Clinicopathological Feature | CDH1-Altered ILC (n = 201) | CDH1-Unaltered ILC (n = 192) | p-Value |
---|---|---|---|
Age | |||
Mean | 63.1 | 62.1 | 0.51 |
Minimum | 37 | 27 | |
Maximum | 90 | 71 | |
Site | |||
Left, n (%) | 89 (50.0) | 88 (55.3) | 0.38 |
Right, n (%) | 89 (50.0) | 71 (44.7) | |
N/A | 23 | 33 | |
Menopausal status | |||
Pre, n (%) | 20 (11.9) | 30 (19.9) | 0.07 |
Post, n (%) | 148 (88.1) | 121 (80.1) | |
N/A | 33 | 41 | |
T factor | |||
T1, n (%) | 42 (23.6) | 39 (25.2) | 0.99 |
T2, n (%) | 92 (51.7) | 79 (51.0) | |
T3, n (%) | 43 (24.2) | 36 (23.2) | |
T4, n (%) | 1 (0.6) | 1 (0.6) | |
N/A | 23 | 37 | |
N factor | |||
N0, n (%) | 58 (53.2) | 36 (40.0) | 0.07 |
N1, n (%) | 22 (20.2) | 33 (36.7) | |
N2, n (%) | 10 (9.2) | 8 (8.9) | |
N3, n (%) | 19 (17.4) | 13 (14.4) | |
N/A | 92 | 102 | |
Tumor grade | |||
Grade 1, n (%) | 6 (7.1) | 11 (11.5) | 0.38 |
Grade 2, n (%) | 54 (63.5) | 52 (54.2) | |
Grade 3, n (%) | 25 (29.4) | 33 (34.4) | |
N/A | 116 | 96 | |
TMB | |||
Mean | 5.6 | 4.2 | 0.05 |
SD | 9.5 | 44.8 | |
Median | 2.6 | 2.5 | |
Minimum | 0 | 0 | |
Maximum | 103.1 | 28.8 | |
TMB-low (<10) (%) | 169 (84.1) | 159 (88.3) | 0.29 |
TMB-high (≥10) (%) | 32 (15.9) | 21 (11.7) | |
N/A | 0 | 12 |
TCGA | METABRIC | |||||
---|---|---|---|---|---|---|
Subtype | CDH1-Altered (n = 110) | CDH1-Unaltered (n = 91) | p-Value | CDH1-Altered (n = 91) | CDH1-Unaltered (n = 101) | p-Value |
Luminal A, n (%) | 95 (88.8) | 39 (70.9) | 0.06 | 38 (53.5) | 26 (35.1) | <0.05 |
Luminal B, n (%) | 4 (3.7) | 7 (12.7) | 14 (19.7) | 8 (10.8) | ||
Her2, n (%) | 2 (1.9) | 1 (1.8) | 6 (8.6) | 8 (10.8) | ||
Basal, n (%) | 1 (0.9) | 1 (1.8) | 0 (0) | 4 (5.4) | ||
Normal-like, n (%) | 5 (4.7) | 7 (12.7) | 11 (15.5) | 15 (20.3) | ||
Claudin-low, n (%) | Blank | Blank | 2 (2.8) | 13 (17.6) | ||
N/A | 3 | 36 | 20 | 27 |
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Uchida, S.; Sugino, T. Insights into E-Cadherin Impairment in CDH1-Unaltered Invasive Lobular Carcinoma: A Comprehensive Bioinformatic Study. Int. J. Mol. Sci. 2024, 25, 8961. https://doi.org/10.3390/ijms25168961
Uchida S, Sugino T. Insights into E-Cadherin Impairment in CDH1-Unaltered Invasive Lobular Carcinoma: A Comprehensive Bioinformatic Study. International Journal of Molecular Sciences. 2024; 25(16):8961. https://doi.org/10.3390/ijms25168961
Chicago/Turabian StyleUchida, Shiro, and Takashi Sugino. 2024. "Insights into E-Cadherin Impairment in CDH1-Unaltered Invasive Lobular Carcinoma: A Comprehensive Bioinformatic Study" International Journal of Molecular Sciences 25, no. 16: 8961. https://doi.org/10.3390/ijms25168961