Matrix Metalloproteinase-9 as Prognostic Factor for the Treatment of HER-2 Enriched Breast Cancer.

BACKGROUND: MMP-9 plays a significant role in invasion and migration of tumor cells and metastasis. A combination MMP-9 biomarker with HER2 and Ki-67 is expected to provide more specificity in prognosis for better breast cancer (BC) treatment options. METHODS: A retrospective cohort of 34 patients with HER2 enriched breast cancer were studied from January 2016 until December 2020. Assessment MMP-9 by IHC using Monoclonal Mouse Anti-Human MMP-9 Antigen with semiquantitative immunoreactive scores methods was done. RESULTS: The samples included patients aged 29 to 66 years. Patients' educational level was mostly high school graduation (n=17; 50%). Distant metastases occurred in 10 (29.4%) patients,  histopathological Grade II was found in 29 (85.7%) patients, positive LVI was found in 18 (52.9%) patients, and high proliferation rate (Ki67 > 20%) was found in 32 (94.1%) patients. All the patients underwent MRM with a history of chemotherapy in 29 (85.3%) patients, radiotherapy in 14 (41.2%) patients, and targeted therapy in only seven (20.6%) patients. Most of the patients had locally advanced stage III (n=21; 61.8%). The MMP-9 High expression was found in 20 (58.8%) patients and 14 (41.2%) patients had a low expression. A significant relationship was found between MMP-9 expression and DFS (p=0.023); while a significant relationship was found with OS (p=0.093). The mean DFS for High expression MMP-9 was 37.3 months and 45.3 months for low expression. The mean OS was 37.6 months for High-intensity MMP-9 and 42.7 months for Low-intensity. CONCLUSIONS: The MMP-9 expression (p=0.037), age group<40 years old (p=0.024), and the history of radiotherapy (p=0.035) were significantly related to he occurrence of distant metastases. The MMP-9 High expression had a 7.5 times greater risk of distant metastases. IMPACTS: The MMP-9 can be used as a prognostic factor for distant metastasis in HER2 Enriched BC.

Cancer-associated fibroblast (CAF) secretomes-induced epithelial-mesenchymal transition on HT-29 colorectal carcinoma cells associated with hepatocyte growth factor (HGF) signalling.

OBJECTIVE: The aim of this study was to investigate the effect of cancer-associated fibroblasts (CAF) secretomes on the epithelial-mesenchymal transition (EMT) of colorectal carcinoma (CRC) cells and its association with hepatocyte growth factor (HGF) signalling focussing on the HGF receptor, c-Mesenchymal epithelial transition (c-Met), and the EMT markers, vimentin and e-cadherin, in CRC cells. METHODS: Conditioned mediums (CM) containing secretomes from colorectal CAFs and their counterpart normal fibroblasts (NFs) of three CRC patients were collected and supplemented to the HT-29 CRC cells. The mRNA levels of a-smooth muscle actin (a-SMA) and HGF in both fibroblasts, as well as c-Met, vimentin, and e-cadherin in HT-29 cells after supplemented with CAF- and NF-CM were determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). HGF protein level in the CM of CAFs and NFs was measured using enzyme-linked immunosorbent assay (ELISA). Vimentin and e-cadherin protein expressions were observed in HT-29 cells using immunofluorescent (IF) staining. RESULTS: Compared to the non-cancerous colon, fibroblasts from cancerous area of CRC substantially expressed higher mRNA levels of a-SMA, a CAF marker. The HGF mRNA expressions in CAFs and NFs were in line with the HGF protein level in the secretomes of both cells. CAF-CM increased c-Met and vimentin mRNA levels in HT-29 cells. Surprisingly, e-cadherin mRNA level in HT-29 cells was increased following CAF-CM supplementation. We also demonstrated the co-localization of e-cadherin and vimentin in the HT-29 cell cytoplasm. CONCLUSIONS: CAF secretomes of CRC promote a hybrid type of EMT associated with HGF signalling.