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. 2019 Dec 2;11(23):11124-11135.
doi: 10.18632/aging.102514. Epub 2019 Dec 2.

JAK1 as a prognostic marker and its correlation with immune infiltrates in breast cancer

Bo Chen  1 , Jianguo Lai  1 , Danian Dai  1 , Rong Chen  2 , Xuan Li  2 , Ning Liao  1
Affiliations

JAK1 as a prognostic marker and its correlation with immune infiltrates in breast cancer

Bo Chen et al. Aging (Albany NY). .

Abstract

Clinical trials testing Janus kinase-1 (JAK1) inhibitors in cancers are under way. Whether the JAK1 mRNA levels in breast tumors correlates with outcome has not been evaluated. JAK1 expression was analyzed via the Oncomine database and Tumor IMmune Estimation Resource site. Tumor tissues from 57 breast cancer patients were used for qRT-PCR and immune infiltration assessment. JAK1 expression was significantly lower in breast invasive carcinoma compared with adjacent normal tissues. Public databases (Kaplan-Meier plotter and PrognoScan) showed that low JAK1 expression was associated with poorer survival. Data from The Cancer Genome Atlas (TCGA) showed that high JAK1 expression was associated with increased survival in both TNM I-II and TNM III-IV patients. JAK1 was inversely correlated with tumor size status, lymph node status, and TNM of breast cancer patients. JAK1 levels were correlated with the T cell transcript-enriched LYM metagene signature and was significantly lower in the low tumor infiltrating lymphocytes (TILs) group. JAK1 expression levels had significant positive correlations with infiltrating levels of CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in breast cancer and not with other B cells. In conclusion, JAK1 mRNA levels were correlated with prognosis and immune infiltrating levels in breast cancer.

Keywords: JAK1; TIL; breast cancer; immune infiltrates; prognosis.

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Conflict of interest statement

CONFLICTS OF INTEREST: No potential conflicts of interest were disclosed.

Figures

Figure 1
Figure 1
JAK1 expression levels in human cancers. (A) JAK1 in data sets of different cancers in the Oncomine database. (B) JAK1 expression levels in different tumor types from TCGA database were determined by TIMER (*P < 0.05, **P <0.01, ***P < 0.001).
Figure 2
Figure 2
Kaplan-Meier survival curves comparing the high and low expression of JAK1 in breast cancer. In the Kaplan-Meier plotter database, high JAK1 expression was correlated with good. (A) RFS (HR[95% CI] = 0.75[0.67-0.85], P = 3e-06) (B) DMFS (HR[95% CI] = 0.6[0.49-0.74], P = 1.4e-06) and (C) OS (HR[95% CI] = 0.52[0.42-0.65], P = 1.5e-09). In TCGA data, high JAK1 expression was also correlated with good OS. (D) All breast cancers (P = 0.0030), (E) TNM I-II (P = 0.038) (F) TNM III-IV (P = 0.013).
Figure 3
Figure 3
JAK1 mRNA levels associated with tumor infiltrating lymphocytes. (A) The average expression of the LYM metagene signature (SASH3, CD53, NCKAP1L, LCP2, IL10RA, PTPRC, EVI2B, BIN2, WAS, and HAVCR2) in each breast cancer sample from TCGA is shown relative to JAK1 mRNA. (B) JAK1 mRNA levels are shown relative to levels of tumor infiltrating lymphocytes in 57 breast cancer samples.
Figure 4
Figure 4
Correlation of JAK1 expression with immune infiltration level in the TIMER database. (A) Other than B cells, JAK1 expression has a significant positive correlation with infiltrating levels of CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in breast cancer. TIMER database analysis in (B) basal, (C) HER2 and (D) luminal subtypes.
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