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Table S3 from The Capacity of the Ovarian Cancer Tumor Microenvironment to Integrate Inflammation Signaling Conveys a Shorter Disease-free Interval

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posted on 2023-03-31, 22:13 authored by Kimberly R. Jordan, Matthew J. Sikora, Jill E. Slansky, Angela Minic, Jennifer K. Richer, Marisa R. Moroney, Junxiao Hu, Rebecca J. Wolsky, Zachary L. Watson, Tomomi M. Yamamoto, James C. Costello, Aaron Clauset, Kian Behbakht, T. Rajendra Kumar, Benjamin G. Bitler

Nanostring transcriptomic data for all genes include on the PanCancer IO 360 Panel and Reverse Protein Phase Array for GTFB 1064 and 1066 (pre and post-NACT).

Funding

Cancer League of Colorado

Colorado Clinical & Translational Sciences Institute

NIH

NCI

Department of Defense

MD Anderson Cancer Center

University of Colorado Cancer Center

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ARTICLE ABSTRACT

Ovarian cancer has one of the highest deaths to incidence ratios across all cancers. Initial chemotherapy is effective, but most patients develop chemoresistant disease. Mechanisms driving clinical chemo-response or -resistance are not well-understood. However, achieving optimal surgical cytoreduction improves survival, and cytoreduction is improved by neoadjuvant chemotherapy (NACT). NACT offers a window to profile pre- versus post-NACT tumors, which we used to identify chemotherapy-induced changes to the tumor microenvironment. We obtained matched pre- and post-NACT archival tumor tissues from patients with high-grade serous ovarian cancer (patient, n = 6). We measured mRNA levels of 770 genes (756 genes/14 housekeeping genes, NanoString Technologies), and performed reverse phase protein array (RPPA) on a subset of matched tumors. We examined cytokine levels in pre-NACT ascites samples (n = 39) by ELISAs. A tissue microarray with 128 annotated ovarian tumors expanded the transcriptional, RPPA, and cytokine data by multispectral IHC. The most upregulated gene post-NACT was IL6 (16.79-fold). RPPA data were concordant with mRNA, consistent with elevated immune infiltration. Elevated IL6 in pre-NACT ascites specimens correlated with a shorter time to recurrence. Integrating NanoString (n = 12), RPPA (n = 4), and cytokine (n = 39) studies identified an activated inflammatory signaling network and induced IL6 and IER3 (immediate early response 3) post-NACT, associated with poor chemo-response and time to recurrence. Multiomics profiling of ovarian tumor samples pre- and post-NACT provides unique insight into chemo-induced changes to the tumor microenvironment. We identified a novel IL6/IER3 signaling axis that may drive chemoresistance and disease recurrence.

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