FGFR的4个基因在TCGA数据库的BRCA里面的生存情况

名词解释：
Cases completely negative (less than 1 % staining) for FGFR1 immunostaining
H-score of 100 or more immunostaining
FGFR is a receptor tyrosine kinase with four key members (FGFR1 to FGFR4)
disease-free survival (DFS) and overall survival (OS)

该研究对TNBC cell lines进行了免疫组化

Positive immunostaining threshold cut-offs for ER(estrogen receptor) and PR(progesterone receptor) are at least 1 % of cells with unequivocal nuclear staining of any intensity.

For the purpose of data analysis, both total percentage of cells stained and immunoreactive H-scores were derived. Immunoreactive H-score was calculated using the formula: (3 × percentage strong staining) +(2 × percentage moderate staining) +(1 × percentage weak staining).

并设置了阈值：Thresholds were defined as at least 1 % of cells stained and H-score of 100 or more .

Multivariate Cox regression analysis showed FGFR1 expression in TNBCs to be independently prognostic for overall survival (OS) at both thresholds.

发现 Cases completely negative (less than 1 % staining) for FGFR1 immunostaining showed improved OS, while those with H-score of 100 or more immunostaining had the worst OS.

FGFR (fibroblast growth factor receptor) 原文应该讲的很明白

FGFR is a receptor tyrosine kinase with four key members (FGFR1 to FGFR4) that play important roles in normal physiology and development. Their expression in different cell types and context gives rise to varying responses,ranging from promotion of cell survival, cell growth,motility and migration, to growth cessation and differentiation. FGFRs are believed to have a role in carcinogenesis,which may be induced by amplifications, point mutations, and/or translocations. FGFR1 and FGFR2 gene amplifications have been reported in some breast cancers, the former being more likely seen in ER-positive cancers, while the latter has been reported in TNBCs.

以下为分子等方面的解释：

The protein encoded by this gene is a member of the fibroblast growth factor receptor (FGFR) family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member binds both acidic and basic fibroblast growth factors and is involved in limb induction. Mutations in this gene have been associated with Pfeiffer syndrome, Jackson-Weiss syndrome, Antley-Bixler syndrome, osteoglophonic dysplasia, and autosomal dominant Kallmann syndrome 2. Chromosomal aberrations involving this gene are associated with stem cell myeloproliferative disorder and stem cell leukemia lymphoma syndrome. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized.

In cancer research, various types of survival rate can be relevant, depending on the cancer type and stage. There are 3 types：disease-free survival、the progression-free survival and the metastasis-free survival .Definition are as follows.

1.the disease-free survival (DFS) :the period after curative treatment [disease eliminated] when no disease can be detected.

2.the progression-free survival (PFS) :the period after treatment when disease [which could not be eliminated] remains stable, that is, does not progress.

3.the metastasis-free survival (MFS) or distant metastasis–free survival (DMFS) :the period until metastasis is detected.

Progression can be categorized as local progression, regional progression, locoregional progression, and metastatic progression.

Overall survival
Patients with a certain disease (for example, HCC) can die directly from that disease or from an unrelated cause (for example, a car accident). When the precise cause of death is not specified, this is called the overall survival rate or observed survival rate. Doctors often use mean overall survival rates to estimate the patient's prognosis. This is often expressed over standard time periods, like one, five, and ten years. For example, prostate cancer has a much higher one-year overall survival rate than pancreatic cancer, and thus has a better prognosis.

Sometimes the overall survival is reported as a death rate (%) without specifying the period the % applies to (possibly one year) or the period it is averaged over (possibly 5 years).

临床资料：
Clinicopathological parameters recorded comprised age, ethnicity, tumor size, histological grade and its constituent parameters (tubule formation, nuclear pleomorphism, and mitotic activity), tumor subtype, associated ductal carcinoma in situ (DCIS), presence of lymphovascular invasion, and axillary lymph node metastasis, as well as disease recurrence and death.

使用oncolnc工具画FGFR4个基因亚型在TCGA-BRCA的生存曲线