 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Oct 15, 2020 |
| Title |
Assessing biosimilarity of Trastuzumab monoclonal antibody therapeutics using RNA sequencing |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Patents of some therapeutic monoclonal antibodies (mAb) used for cancer treatment are ending soon, allowing for the entry of similar analogs (biosimilars) onto the market. To have a biosimilar approved by health agencies, the manufacturer must typically demonstrate functional and physicochemical similarity between the biosimilar and the approved reference product. Functional similarity is often validated with cell-based assays, but the information gained is limited. In contrast, RNA-seq methods enable a sensitive transcriptomic analysis, providing detailed information on pathways and cellular responses. Trastuzumab inhibits signaling of the cell-surface receptor HER2, which is overexpressed in approximately 30% of all breast cancer patients. Here, we compare the functional effect of the mAb Trastuzumab and a corresponding biosimilar. The BT-474 breast cancer cell line was treated with the reference product, Trastuzumab (Herceptin®), or a proposed biosimilar (ApoTras), and the cellular transcriptomes were analyzed by RNA-seq. Functional similarity was assessed using two statistical contrasts. One contrast evaluated the mechanism of action by comparing treated samples (Her and ApoTras, n = 19) vs. untreated controls (n = 10), which identified 2623 differentially expressed genes (DEG) at a minimum fold change of 1.25. The other contrast directly compared ApoTras (n = 9) vs. Her (n = 10) to determine differences in expression between treatments and identified 24 DEG using a 1.25 fold- change threshold. This low DEG number reveals a very high similarity of effect of both mAb treatments on the cancer cells. A gene set overrepresentation analysis of DEG for mAb treatments revealed mechanisms of action, which were consistent with known trastuzumab effects. Supporting the small number of changes between both treatments, a post-hoc power analysis for the between-treatment comparison estimated power of 0.88 to detect a gene expression fold-changes of 2.0. To summarize these data, we introduce an overall similarity index (SI) to quantify treatment similarity based on changes in gene expression. Using statistical contrasts with RNA-seq analysis provides a powerful tool for the comparison of biological effects of biosimilar and originator compounds and can be broadly used for functional comparisons of drug treatments.
|
| |
|
| Overall design |
We compared changes in gene expression of mRNAs in BT-474 cells untreated or treated with Herceptin or a biosimilar of it by RNA-seq. Paired-End Sequencing of samples with Illumina HiSeq Sequencing
|
| |
|
| Contributor(s) |
Rinas K, McConkey B, Mooney S |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Oct 03, 2020 |
| Last update date |
Oct 06, 2020 |
| Contact name |
Karsten Rinas |
| E-mail(s) |
krinas@uwaterloo.ca
|
| Organization name |
University of Waterloo
|
| Department |
Biology
|
| Lab |
Brendan J McConkey
|
| Street address |
200 University Ave W
|
| City |
Waterloo |
| State/province |
ON |
| ZIP/Postal code |
N2L3G1 |
| Country |
Canada |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (30)
|
| GSM4816746 |
Untreated Control mRNA sample, replicate 1 |
| GSM4816747 |
Untreated Control mRNA sample, replicate 2 |
| GSM4816748 |
Untreated Control mRNA sample, replicate 3 |
| GSM4816749 |
Untreated Control mRNA sample, replicate 4 |
| GSM4816750 |
Untreated Control mRNA sample, replicate 5 |
| GSM4816751 |
Untreated Control mRNA sample, replicate 6 |
| GSM4816752 |
Untreated Control mRNA sample, replicate 7 |
| GSM4816753 |
Untreated Control mRNA sample, replicate 8 |
| GSM4816754 |
Untreated Control mRNA sample, replicate 9 |
| GSM4816755 |
Untreated Control mRNA sample, replicate 10 |
| GSM4816756 |
Herceptin treated mRNA sample, replicate 1 |
| GSM4816757 |
Herceptin treated mRNA sample, replicate 2 |
| GSM4816758 |
Herceptin treated mRNA sample, replicate 3 |
| GSM4816759 |
Herceptin treated mRNA sample, replicate 4 |
| GSM4816760 |
Herceptin treated mRNA sample, replicate 5 |
| GSM4816761 |
Herceptin treated mRNA sample, replicate 6 |
| GSM4816762 |
Herceptin treated mRNA sample, replicate 7 |
| GSM4816763 |
Herceptin treated mRNA sample, replicate 8 |
| GSM4816764 |
Herceptin treated mRNA sample, replicate 9 |
| GSM4816765 |
Herceptin treated mRNA sample, replicate 10 |
| GSM4816766 |
Biosimilar treated mRNA sample, replicate 1 |
| GSM4816767 |
Biosimilar treated mRNA sample, replicate 2 |
| GSM4816768 |
Biosimilar treated mRNA sample, replicate 3 |
| GSM4816769 |
Biosimilar treated mRNA sample, replicate 4 |
| GSM4816770 |
Biosimilar treated mRNA sample, replicate 5 |
| GSM4816771 |
Biosimilar treated mRNA sample, replicate 6 |
| GSM4816772 |
Biosimilar treated mRNA sample, replicate 7 |
| GSM4816773 |
Biosimilar treated mRNA sample, replicate 8 |
| GSM4816774 |
Biosimilar treated mRNA sample, replicate 9 |
| GSM4816775 |
Biosimilar treated mRNA sample, replicate 10 |
|
| Relations |
| BioProject |
PRJNA667165 |
| SRA |
SRP286256 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE158969_RSEM_expected_counts.xlsx |
7.0 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...