Key words: cytokine; IL-8; protein arrays; breast cancer; estrogen receptor; tumor progressionCytokines, cell communication mediators, play important roles in a wide range of physiological processes, such as cell growth, differentiation, apoptosis, wound healing and homeostasis. 1 A wealth of evidences suggests that cytokines, growth factors, chemokines, angiogenic factors and proteases are involved in cancer progression. 2-5 A number of autocrine and paracrine cytokine loops influence tumor development. 6 -9 Cytokines not only provide defense against cancer cells, but also promote cancer cell growth at every stage of cancer development. 10 Alteration of cytokine levels is associated with cancer progression, 11,12 response to chemotherapy 13,14 and metastatic status. 15,16 Therefore, determination of these factors in human breast cancer cells will shed light on the development of human breast cancer, identify new molecular targets for developing effective agents against breast cancer, discover biomarkers to aid in diagnosis and to predict clinical outcome, and eventually provide guideline for individual therapy. Furthermore, despite recent improvements in curing breast cancer patients, breast cancer still remains a serious threat to women's lives. Therefore, it is imperative to identify new targets for the development of effective treatment strategy. Because of the limitation of technology, however, previous studies only measured single or few cytokines at once. This greatly limits our understanding of the roles of those factors in breast cancer and the potential application in clinical diagnosis and prediction of clinical outcome.We recently developed several novel cytokine antibody array systems, which allow investigators to detect multiple cytokine expression levels simultaneously with high specificity and sensitivity. [17][18][19][20] By using human cytokine antibody array technology, we have begun to analyze differential cytokine expression levels in various human cancers, including human breast cancer, with the goal to identify key factor(s) involved in human breast cancer progression. Human cytokine antibody arrays indicate that expression of IL-8 is linked to ER status, metastasis status and vimentin status. Tumor biology experiments suggest that IL-8 is involved in breast cancer cell invasion and angiogenesis. Furthermore, ER␣ directly downregulates IL-8 expression. Our results suggest a potential new pathway involved in ER␣ inaction and upregulation of IL-8, leading to the invasiveness and angiogenesis of human breast cancer.

Key Points Question Is the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to primary cytoreductive surgery (PCS) associated with better outcomes for patients with stage III epithelial ovarian cancer? Findings In this multicenter retrospective cohort study of 584 patients with stage III epithelial ovarian cancer, for patients undergoing PCS with HIPEC and those undergoing PCS alone, the median overall survival was 49.8 and 34.0 months, respectively, and the 3-year overall survival rates were 60.3% and 49.5%, respectively. Complete PCS with HIPEC was associated with the best survival outcomes, with a median overall survival of 53.9 months and a 3-year overall survival rate of 65.9%. Meaning In this study, the addition of HIPEC to PCS was associated with better survival outcomes for patients with stage III epithelial ovarian cancer.

Ovarian cancer is the most common and lethal gynecological tumor in women worldwide. High-grade serous ovarian carcinoma (HGSOC) is one of the histological subtypes of epithelial ovarian cancer, accounting for 70%. It often occurs at later stages associated with a more fatal prognosis than endometrioid carcinomas (EC), another subtype of epithelial ovarian cancer. However, the molecular mechanism and biology underlying the metastatic HGSOC (HG_M) immunophenotype remain poorly elusive. Here, we performed single-cell RNA sequencing analyses of primary HGSOC (HG_P) samples, metastatic HGSOC (HG_M) samples, and endometrioid carcinomas (EC) samples. We found that ERBB2 and HOXB-AS3 genes were more amplified in metastasis tumors than in primary tumors. Notably, high-grade serous ovarian cancer metastases are accompanied by dysregulation of multiple pathways. Malignant cells with features of epithelial-mesenchymal transition (EMT) affiliated with poor overall survival were identified. In addition, cancer-associated fibroblasts with EMT-program were enriched in HG_M, participating in angiogenesis and immune regulation, such as IL6/STAT3 pathway activity. Compared with ECs, HGSOCs exhibited higher T cell infiltration. PRDM1 regulators may be involved in T cell exhaustion in ovarian cancer. The CX3CR1_macro subpopulation may play a role in promoting tumor progression in ovarian cancer with high expression of BAG3, IL1B, and VEGFA. The new targets we discovered in this study will be useful in the future, providing guidance on the treatment of ovarian cancer.

No abstract