Limits...
A 3q gene signature associated with triple negative breast cancer organ specific metastasis and response to neoadjuvant chemotherapy

View Article: PubMed Central - PubMed

ABSTRACT

Triple negative breast cancers (TNBC) are aggressive tumors, with high rates of metastatic spread and targeted therapies are critically needed. We aimed to assess the prognostic and predictive value of a 3q 19-gene signature identified previously from lung cancer in a collection of 4,801 breast tumor gene expression data. The 3q gene signature had a strong association with features of aggressiveness such as high grade, hormone receptor negativity, presence of a basal-like or TNBC phenotype and reduced distant metastasis free survival. The 3q gene signature was strongly associated with lung metastasis only in TNBC (P < 0.0001, Hazard ratio (HR) 1.44, 95% confidence interval (CI), 1.31–1.60), significantly associated with brain but not bone metastasis regardless of TNBC status. The association of one 3q driver gene FXR1 with distant metastasis in TNBC (P = 0.01) was further validated by immunohistochemistry. In addition, the 3q gene signature was associated with better response to neoadjuvant chemotherapy in TNBC (P < 0.0001) but not in non-TNBC patients. Our study suggests that the 3q gene signature is a novel prognostic marker for lung and/or brain metastasis and a predictive marker for the response to neoadjuvant chemotherapy in TNBC, implying a potential role for 3q genes in the mechanism of organ-specific metastasis.

No MeSH data available.


Related in: MedlinePlus

The 3q 19-gene signature is associated with Basal-like and Luminal B subtypes of breast cancer.PAM50 subtypes of 4801 tumors were calculated using genefu R package. P value was calculated using Kruskal–Wallis analysis of variance analysis (ANOVA).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5384279&req=5

f1: The 3q 19-gene signature is associated with Basal-like and Luminal B subtypes of breast cancer.PAM50 subtypes of 4801 tumors were calculated using genefu R package. P value was calculated using Kruskal–Wallis analysis of variance analysis (ANOVA).

Mentions: Among the 4,801 patients with breast cancer, we tested the association between the 3q 19-gene signature and established prognostic variables including age, grade, tumor size, lymph node status, and the expression status of ER, PR and HER2. The 3q gene signature was significantly associated with higher grade (P < 2.2e-16), larger tumor size (P = 0.005), ER- (P = 1.42e-08) and PR- status (P = 4.75e-10), but not associated with age (P = 0.07), HER2 status (P = 0.53) or lymph node involvement (P = 0.26) (Table 1 and Supplemental Fig. 1). The 3q gene signature was significantly associated with basal-like and luminal B subtypes of breast tumors (P < 2.2e-16, Fig. 1) or TNBC (P = 3.06e-12, Supplemental Fig. 1). Moreover, both univariable Cox analysis and a meta-analysis indicated that the high 3q gene signature was significantly associated with worse distant metastasis–free survival (DMFS) (P = 3.25e-05), but not recurrence-free survival (RFS) (P = 0.07), OS (P = 0.29) or DSS (P = 0.24) (Table 1 and Supplemental Figs 2 and 3).


A 3q gene signature associated with triple negative breast cancer organ specific metastasis and response to neoadjuvant chemotherapy
The 3q 19-gene signature is associated with Basal-like and Luminal B subtypes of breast cancer.PAM50 subtypes of 4801 tumors were calculated using genefu R package. P value was calculated using Kruskal–Wallis analysis of variance analysis (ANOVA).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5384279&req=5

f1: The 3q 19-gene signature is associated with Basal-like and Luminal B subtypes of breast cancer.PAM50 subtypes of 4801 tumors were calculated using genefu R package. P value was calculated using Kruskal–Wallis analysis of variance analysis (ANOVA).
Mentions: Among the 4,801 patients with breast cancer, we tested the association between the 3q 19-gene signature and established prognostic variables including age, grade, tumor size, lymph node status, and the expression status of ER, PR and HER2. The 3q gene signature was significantly associated with higher grade (P < 2.2e-16), larger tumor size (P = 0.005), ER- (P = 1.42e-08) and PR- status (P = 4.75e-10), but not associated with age (P = 0.07), HER2 status (P = 0.53) or lymph node involvement (P = 0.26) (Table 1 and Supplemental Fig. 1). The 3q gene signature was significantly associated with basal-like and luminal B subtypes of breast tumors (P < 2.2e-16, Fig. 1) or TNBC (P = 3.06e-12, Supplemental Fig. 1). Moreover, both univariable Cox analysis and a meta-analysis indicated that the high 3q gene signature was significantly associated with worse distant metastasis–free survival (DMFS) (P = 3.25e-05), but not recurrence-free survival (RFS) (P = 0.07), OS (P = 0.29) or DSS (P = 0.24) (Table 1 and Supplemental Figs 2 and 3).

View Article: PubMed Central - PubMed

ABSTRACT

Triple negative breast cancers (TNBC) are aggressive tumors, with high rates of metastatic spread and targeted therapies are critically needed. We aimed to assess the prognostic and predictive value of a 3q 19-gene signature identified previously from lung cancer in a collection of 4,801 breast tumor gene expression data. The 3q gene signature had a strong association with features of aggressiveness such as high grade, hormone receptor negativity, presence of a basal-like or TNBC phenotype and reduced distant metastasis free survival. The 3q gene signature was strongly associated with lung metastasis only in TNBC (P&thinsp;&lt;&thinsp;0.0001, Hazard ratio (HR) 1.44, 95% confidence interval (CI), 1.31&ndash;1.60), significantly associated with brain but not bone metastasis regardless of TNBC status. The association of one 3q driver gene FXR1 with distant metastasis in TNBC (P&thinsp;=&thinsp;0.01) was further validated by immunohistochemistry. In addition, the 3q gene signature was associated with better response to neoadjuvant chemotherapy in TNBC (P&thinsp;&lt;&thinsp;0.0001) but not in non-TNBC patients. Our study suggests that the 3q gene signature is a novel prognostic marker for lung and/or brain metastasis and a predictive marker for the response to neoadjuvant chemotherapy in TNBC, implying a potential role for 3q genes in the mechanism of organ-specific metastasis.

No MeSH data available.


Related in: MedlinePlus