Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer

Abstract

SUMMARY To provide a detailed analysis of the molecular components and underlying mechanisms associated with ovarian cancer, we performed a comprehensive mass spectrometry-based proteomic characterization of 174 ovarian tumors previously analyzed by The Cancer Genome Atlas (TCGA), of which 169 were high-grade serous carcinomas (HGSC). Integrating our proteomic measurements with the genomic data yielded a number of insights into disease such as how different copy number alternations influence the proteome, the proteins associated with chromosomal instability, the sets of signaling pathways that diverse genome rearrangements converge on, as well as the ones most associated with short overall survival. Specific protein acetylations associated with homologous recombination deficiency suggest a potential means for stratifying patients for therapy. In addition to providing a valuable resource, these findings provide a view of how the somatic genome drives the cancer proteome and associations between protein and post-translational modification levels and clinical outcomes in HGSC.

Deconstruction of a Metastatic Tumor Microenvironment Reveals a Common Matrix Response in Human Cancers

“…We found a strong association between the density of α-SMA and α-FAP positive cells, two markers commonly associated with activation of cancer associated fibroblasts, and disease score and there are several examples in the literature of poor prognostic fibroblast, desmoplastic, wound healing and stromal signatures in individual cancer types e.g. (39,59). As fibroblasts are the predominant matrix producing cells in many tissues this may, at least partially, explain the commonality of the matrix index in different cancers.…”

Recurrent ubiquitin B silencing in gynecological cancers establishes dependence on ubiquitin C

“…The mainstay treatment for women with high-grade serous ovarian cancer (HGSOC) remains cisplatin, which was introduced in the late 1970s (8), and while survival rates have largely unchanged since then (9), emerging therapeutic strategies that include surgical improvements, use of anti-VEGF antibodies, and recent approvals for PARP inhibitors indicate that significant progress is being made (10)(11)(12). While profiling in HGSOC has led to important insights for the molecular classification of ovarian cancer subtypes, there persists a gap at the level of finding lesions that act as oncogenic drivers and are validated as clinically relevant targets in these patients (13)(14)(15). Synthetic lethality, commonly based on tumor suppressor loss, emerges as an alternative approach.…”

Responses of Dynamic Proteome Changes in Zizania Latifolia to Fresh-Cut Operation during Room Temperature (25 °C) Storage

“…20 As a signaling element, small ras-related GTP-binding proteins meditate various external stimuli to intracellular signaling pathways. 21,22 All of them decreased during the storage of whole Z. latifolia; however, spot 10 and spot 38 were up-regulated by fresh-cut operation, suggesting that signal transduction was enhanced.…”