FGFR的4個(gè)基因在TCGA數(shù)據(jù)庫的BRCA里面的生存情況

名詞解釋:
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)


該研究對TNBC cell lines進(jìn)行了免疫組化

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).

并設(shè)置了閾值: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.

發(fā)現(xiàn) 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) 原文應(yīng)該講的很明白

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.

以下為分子等方面的解釋:

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).

臨床資料:
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工具畫FGFR4個(gè)基因亞型在TCGA-BRCA的生存曲線


FGFR1

FGFR2

FGFR3

FGFR4

以上依次為FGFR1、2、3、4的生存曲線,可見與對照組相比,高表達(dá)FGFR1和2的病人在3000天之后生存率明顯降低,而FGFR3在接近4000天時(shí)生存率明顯下降,F(xiàn)GFR4明顯延伸到了6500天。
同樣使用,UCSC Xena等也可看到類似的情況。


使用SurvExpress看亞型間的生存曲線


FGFR1&FGFR2

參考來源:生信技能樹

友情鏈接:

課程分享
生信技能樹全球公益巡講
https://mp.weixin.qq.com/s/E9ykuIbc-2Ja9HOY0bn_6g
B站公益74小時(shí)生信工程師教學(xué)視頻合輯
https://mp.weixin.qq.com/s/IyFK7l_WBAiUgqQi8O7Hxw
招學(xué)徒:
https://mp.weixin.qq.com/s/KgbilzXnFjbKKunuw7NVfw

歡迎關(guān)注公眾號:青島生信菜鳥團(tuán)

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