Downregulation of miR-106b induced breast cancer cell invasion and motility in association with overexpression of matrix metalloproteinase 2.

Breast cancer (BC) is one of the most common cancers in women, and it can often metastasize to the bone. The mechanism of BC bone metastasis remains unclear and requires in-depth investigation. In a previous study, we found the expression of matrix metalloproteinase 2 (MMP2) to be significantly more pronounced at metastatic bone sites than at orthotopic sites. MicroRNA expression profiling showed miR-106b to be markedly downregulated during BC bone metastasis. However, the specific manner in which MMP2 and miR-106b are involved in the BC bone metastasis is still unclear. In the present study, we found MMP2 expression in orthotopic tumor tissue to be related to the risk of bone metastasis in BC patients. MiR-106b levels in orthotopic tumor tissue showed a negative correlation with MMP2 expression and breast cancer bone metastasis. MMP2 was shown to be a direct target of miR-106b. Both gain- and loss-of-function studies showed that MMP2 could promote the migration and invasion of BC cells and that miR-106b could suppress both. The blockage of MMP2 by RNA interference mimicked the anti-migration and anti-invasion effects of miR-106b, and introduction of MMP2 antagonized the function of miR-106b. MMP2 was also found to regulate the ERK signaling cascade and so adjust the bone microenvironment to favor osteoclastogenesis and bone metastasis. These results suggest that MMP2 upregulation plays an important role in BC bone metastasis through ERK pathways, and miR-106b directly regulates MMP2 expression. The miR-106b/MMP2/ERK pathway may be a promising therapeutic target for inhibiting BC bone metastasis.

Association between bone mineral density and type 1 diabetes mellitus: a meta-analysis of cross-sectional studies.

A few studies have investigated the relationship between type 1 diabetes mellitus (T1DM) and bone mineral density (BMD) values. This meta-analysis was performed to explore differences between T1DM and healthy individuals in BMD values measured at five bone sites.We searched the database of PubMed for cross-sectional studies about the association of T1DM and BMD, and a meta-analysis was conducted.The results suggested significant association between T1DM and decreased BMD values of total body. The pooled mean differences (MDs) were -0.06 [95% confidence interval (CI): -0.11, -0.01] for all people. As for the association between T1DM and spine BMD values, the pooled MDs were -0.04 (95% CI: -0.07, -0.01) for males and -0.03 (95% CI: -0.06, 0.00) for females <20 years old. As for femur BMD values, the pooled MDs were -0.06 (95% CI: -0.13, 0.00) for all people, -0.03 (95% CI: -0.06, -0.01) for females and -0.04(95% CI: -0.05, -0.02) for males. As for hip BMD values, the pooled MDs were -0.06 (95% CI: -0.08, -0.04) for females. As for forearm BMD values, the pooled MDs were -0.01 (95% CI: -0.02, 0.00) for females.The results of this meta-analysis suggest the overall association between T1DM and reduced BMD values. Notably, the influence of T1DM on BMD seems to depend on gender or patient's age. Reduced BMD values may occur early after T1DM diagnosis. Future clinical and basic research studies are needed to further understand the mechanisms of decreased BMD values in T1DM patients.

Risk of breast cancer and family history of other cancers in first-degree relatives in Chinese women: a case control study.

BACKGROUND: Few studies have systematically reported the relationship between the risk of breast cancer and family history of other cancers. This study was designed to systematically determine the relationship between breast cancer risk and family history of other cancers in first-degree relatives. METHODS: Between January 2006 and June 2011, 823 women diagnosed with breast cancer were included, and age-matched women diagnosed with benign breast disease were selected as controls. Family history of other cancers in first-degree relatives was recorded by trained reviewers. Multivariate logistic regression was applied to analyze the relationships. RESULTS: A family history of esophagus cancer (OR: 2.70, 95% CI: 1.11 - 6.57), lung cancer (OR: 2.49 95% CI: 1.10 - 5.65), digestive system cancer (OR: 1.79, 95% CI: 1.14 - 2.79) and any cancer (OR: 2.13, 95% CI: 1.49 - 3.04) in first-degree relatives was directly associated with increased breast cancer risk. In subgroup analysis, the risk of hormone receptor positive breast cancer was increased in subjects with a family history of lung cancer (OR: 3.37, 95% CI: 1.45 - 7.82), while the risk of hormone receptor negative breast cancer was increased in subjects with a family history of esophagus cancer (OR: 6.19, 95% CI: 2.30 - 16.71), uterus cancer (OR: 6.92, 95% CI: 1.12 - 42.89), digestive tract cancer (OR: 2.05, 95% CI: 1.03 - 4.10) and gynecology cancer (OR: 6.79, 95% CI: 1.46 - 31.65). Additionally, a significant increase in breast cancer was observed with a family history of digestive system cancer for subjects 50 y and younger (OR: 1.88, 95% CI: 1.03 - 3.43), not for subjects 50 y older (OR: 1.67, 95% CI: 0.86 - 3.25). CONCLUSIONS: Breast cancer aggregates in families with several types of cancer especially for digestive system cancer. The influence of a family history of other cancers seems more likely to be limited to hormone receptor negative breast cancer.

FTO promotes the progression of bladder cancer via demethylating m6A modifications in PTPN6 mRNA.

Bladder cancer (BC), a highly prevalent malignancy of the urinary system, necessitates further investigation into its progression mechanisms. N6-methyladenosine (m6A) RNA methylation, a prevalent modification in cellular RNA, has been implicated in the tumorigenesis and metastasis of various cancers. In this study, the upregulation of FTO in human BC samples and its association with poor prognosis were demonstrated using immunohistochemistry (IHC) on tissue sections collected from BC patients. The functional role of FTO in promoting the proliferation and metastasis abilities of BC cells was determined using a combination of in vitro and in vivo assays. In vitro, we conducted cell proliferation assays, such as the Cell Counting Kit-8 (CCK-8) assay, and metastasis assays, including the wound healing assay and transwell invasion assay. In vivo, we employed xenograft models to assess tumor growth and metastasis. Furthermore, our investigation into potential FTO targets in BC cells revealed that FTO modifies PTPN6 mRNA, leading to increased stability and expression of PTPN6, thereby enhancing proliferation and metastasis abilities. In conclusion, our findings indicate that FTO serves as an oncogenic factor in BC, suggesting its potential utility as a diagnostic or prognostic biomarker for bladder cancer.

Aldehyde dehydrogenase 1 expression correlates with the invasion of breast cancer.

BACKGROUND: Aldehyde dehydrogenase 1 (ALDH1) is an important marker of tumor-initiating cells. We aimed to investigate ALDH1 expression in benign breast disease and human breast cancer of different histologic stages. METHODS: Immunohistochemical staining of ALDH1 was applied to 21 cases with benign breast diseases, 47 ductal carcinoma in situ (DCIS) cases, 62 cases diagnosed with invasive cancer with extensive intraductal component (EIC), and 58 cases diagnosed with invasive cancer without EIC. RESULTS: ALDH1 was expressed in tumor cells in 61.0% of 164 breast cancer cases, which was higher than that in benign breast disease (3/21) (P < 0.001). Of these 167 breast cancer cases, a significantly higher rate (54/58) of intratumoral ALDH1 expression was observed in invasive cancer without EIC cases than that in DCIS cases (19/46, one case not available) and invasive cancer with EIC cases (27/60, two cases not available) (P < 0.001). Interestingly, a significantly higher rate (22/48) of intratumoral ALDH1 expression in invasive component was observed than that in in situ component (7/48) in the same tumor (P = 0.001). In 47 DCIS cases, no significant association was observed between ALDH1 positivity and any clinicopathological parameter (all P > 0.05). However, ALDH1 positive invasive breast cancers were significantly more likely to be with large tumor size (P = 0.001), high grade (P < 0.001), and high Ki67 expression (P = 0.009). CONCLUSIONS: ALDH1 may play an important role in the invasion of breast cancer, and may be associated with aggressive phenotypes of breast cancer. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1608671725154947 .

Intraoperative ultrasound guidance is associated with clear lumpectomy margins for breast cancer: a systematic review and meta-analysis.

PURPOSE: Margin status is one of the most important predictors of local recurrence after breast conserving surgery (BCS). Intraoperative ultrasound guidance (IOUS) has the potential to improve surgical accuracy for breast cancer. The purpose of the present meta-analysis was to determine the efficacy of IOUS in breast cancer surgery and to compare the margin status to that of the more traditional Guide wire localization (GWL) or palpation-guidance. METHODS: We searched the database of PubMed for prospective and retrospective studies about the impact of IOUS on margin status of breast cancer, and a meta-analysis was conducted. RESULTS: Of the 13 studies included, 8 were eligible for the impact of IOUS on margin status of non-palpable breast cancers, 4 were eligible for palpable breast cancers, and 1 was for both non-palpable and palpable breast cancers. The rate of negative margins of breast cancers in IOUS group was significantly higher than that in control group without IOUS (risk ratio (RR)  = 1.37, 95% confidence interval (CI)  = 1.18-1.59 from 7 prospective studies, odds ratio (OR)  = 2.75, 95% CI  = 1.66-4.55 from 4 retrospective studies). For non-palpable breast cancers, IOUS-guidance enabled a significantly higher rate of negative margins than that of GWL-guidance (RR  = 1.26, 95% CI  = 1.09-1.46 from 6 prospective studies; OR  = 1.45, 95% CI  = 0.86-2.43 from 2 retrospective studies). For palpable breast cancers, relative to control group without IOUS, the RR for IOUS associated negative margins was 2.36 (95% CI  = 1.26-4.43) from 2 prospective studies, the OR was 2.71 (95% CI  = 1.25-5.87) from 2 retrospective studies. CONCLUSION: This study strongly suggests that IOUS is an accurate method for localization of non-palpable and palpable breast cancers. It is an efficient method of obtaining high proportion of negative margins and optimum resection volumes in patients undergoing BCS.

Low serum creatine kinase levels in breast cancer patients: a case-control study.

BACKGROUND: Previous studies provide an ambiguous picture of creatine kinase (CK) expression and activities in malignancy. The aim of this study was to investigate the role of serum CK level in breast cancer patients. PATIENTS AND METHODS: 823 female patients diagnosed with breast cancer were consecutively recruited as cases, and 823 age-match patients with benign breast disease were selected as controls. Serum CK was analyzed by commercially available standardized methods. RESULTS: Serum CK level was significantly associated with breast cancer (P = 0.005) and subtypes of breast cancer, including breast cancer with diameter>2 cm (P = 0.031) and stage IIIbreast cancer (P = 0.025). The mean serum CK level in patients with>2 cm tumor was significantly lower than that in≤2 cm (P = 0.0475), and the mean serum CK level of stage III breast cancer patients was significantly lower than that of stage I and II breast cancer patients (P = 0.0246). Furthermore, a significant difference (P = 0.004) was observed between serum CK level and ERBB2+breast cancer not other molecular subtypes. CONCLUSIONS: Serum CK levels in cases was significantly lower compared with controls. Notably, our results indicated for the first time that there was a negative correlation between serum CK levels and breast cancer stage. Serum CK level, which may reflect the status of host immunity, may be an important factor in determining breast cancer development and progression.