Clinical trial NCT04137406: Role of SIRT1 in Regulation of Epithelial-to-mesenchymal Transition in Breast Cancer Lymph Nodes Metastasis
Official title: Role of SIRT1 in Regulation of Epithelial-to-mesenchymal Transition in Breast Cancer Lymph Nodes Metastasis for Luminal A Subtype
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Breast Cancer
Lymph Node Metastases
Keywords: Luminal A breast cancer
Sirt 1
lymph node metastasis
EMT
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2019-10-24
Enrollment: 160
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: all the patients have invasive breast cancer with luminal A subtype group 1: T1 and lymph node positve group 2: T2/T3 with negative lymph node

Brief summary: Luminal A breast cancer is a kind of breast cancer with low rate lymph node metastasis and good survival. But in clinical practice, Luminal A breast cancer can present with early, unexpected lymph node metastasis some time, indicates poor survival. Silent information regulator 2 homolog 1 (SIRT1) plays a different role in breast cancer with different molecular typing. Previous study supports a role of SIRT1 protein as tumor suppressor in Luminal A breast cancer, in association with apoptosis-related proteins. The epithelial-to-mesenchymal transition(EMT) process results in loss of cell-cell adhesion, increased cell mobility, and is crucial for enabling the metastasis of cancer cells. But no similar study in Luminal A breast cancer. Hence, this study will 1) investigate the expression pattern of SIRT1 in primary tumor and lymph node metastasis; 2) investigate the different expression pattern of SIRT1 in T2/T3 , lymph node negative tumor and T1, lymph node positive tumor; 3) investigate potential role of SIRT1 enzyme in regulating cell migration and invasion in Luminal A breast cancer cells.

Detailed description: The study has three parts.

1. In large specimens of human Luminal A breast cancer with T1 tumor and positive axillary lymph node, study the difference expression of SIRT1 and related p53, Bcl-2, autophagy-related protein caspase-3, apaf-1 between primary tumor and lymph node metastases. Collect 50 pairs of T1 primary tumors and corresponding metastatic lymph node specimens. Using immunohistochemistry, anti-SIRT1, p53, Bcl-2, caspase-3 and apaf-1 antibody staining to identify the expression of above proteins in the primary tumor and lymph node metastases.
2. Eighty patients with Luminal type A breast cancer (T1N+) were enrolled in this study. At the same time,eighty patients were enrolled in the paraffin-embedded specimens of the patients with T2N+ and T3N+,too. And all patients were followed up. Immunohistochemical staining with anti-SIRT1, p53, Bcl-2, caspase-3, apaf-1, E-cadherin, N-cadherin, Vimentin antibodies to determine the relationship between above protein expression and routine clinicopathological and survival.
3. Explore the involvement of SIRT1 in hormone receptor-positive human breast cancer cells at the cellular level. The molecular mechanism of EMT-related protein regulation, which affects the proliferation, invasion and metastasis of tumor cells.

Eligibility criteria: Inclusion Criteria:

* Invasive breast cancer Luminal A subtype T1 and lymph node positive or T2/T3 with negative lymph node

Exclusion Criteria:

* Missing clinical pathology data

Primary outcomes:
measure: Protein expression difference
timeFrame: 2020-2
Secondary outcomes:
measure: survival
timeFrame: 2021-2
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking university people's hospital
state: Beijing
Study officials:
affiliation: Peking University People's Hospital
name: shu wang, Doctor
role: STUDY_DIRECTOR
References: