Prognostic value of kallikrein-related peptidase 12 (KLK12) mRNA expression in triple-negative breast cancer patients

Gong, Weiwei; Liu, Yueyang; Preis, Sarah; Geng, Xiaocong; Petit‐Courty, Agnès; Kiechle, Marion; Muckenhuber, Alexander; Dreyer, Tobias; Dorn, Julia; Courty, Yves; Magdolen, Viktor

doi:10.1186/s10020-020-0145-7

Cited by 10 publications

(5 citation statements)

References 46 publications

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“…119 Moreover, although no significant effect of miR-378a was found on KLK4 expression, both miR-378a and KLK4 represent unfavorable prognostic markers in TNBC patients. 120…”

Section: Breast Cancermentioning

confidence: 99%

Depicting the Implication of miR-378a in Cancers

Qin

Liang

et al. 2022

Technol Cancer Res Treat

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MicroRNA-378a (miR-378a), including miR-378a-3p and miR-378a-5p, are encoded in PPARGC1B gene. miR-378a is essential for tumorigenesis and is an independent prognostic biomarker for various malignant tumors. Aberrant expression of miR-378a affects several physiological and pathological processes, including proliferation, apoptosis, tumorigenesis, cancer invasion, metastasis, and therapeutic resistance. Interestingly, miR-378a has a dual functional role in either promoting or inhibiting tumorigenesis, independent of the cancer type. In this review, we comprehensively summarized the role and regulatory mechanisms of miR-378a in cancer development, hoping to provide a direction for its potential use in cancer therapy.

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“…119 Moreover, although no significant effect of miR-378a was found on KLK4 expression, both miR-378a and KLK4 represent unfavorable prognostic markers in TNBC patients. 120…”

Section: Breast Cancermentioning

confidence: 99%

Depicting the Implication of miR-378a in Cancers

Qin

Liang

et al. 2022

Technol Cancer Res Treat

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“…4 C). This module included genes reportedly involved in tumor progression, invasion and chemoresistance, such as Uroplakin 1B ( UPK1B ) and Kallikrein-related peptidases ( KLK7 , 8 and 12 ) ( Dong et al 2010 ; Kryza et al 2016 ; Wang et al 2018 ; Gong et al 2020 ). To explore oncogenic pathways correlated with the SmCC-like gene module activity (i.e., average of 10 module gene expression levels; see Methods), we performed gene set enrichment analysis (GSEA) using the TCGA HPV-positive OPSqCC data set.…”

Section: Resultsmentioning

confidence: 99%

Genetic and transcriptomic analyses in a rare case of human papillomavirus–related oropharyngeal squamous-cell carcinoma combined with small-cell carcinoma

Sato

Nishiyama

Taguchi

et al. 2021

Cold Spring Harb Mol Case Stud

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Human papillomavirus (HPV)-related oropharyngeal small cell carcinoma (OPSmCC) is a rare malignancy with aggressive behavior, whereas HPV-related oropharyngeal squamous cell carcinoma (OPSqCC) displays a favorable prognosis. Notably, these two malignancies occasionally arise in an identical tumor. In this case study, we explored the molecular characteristics that distinguishes these two carcinomas employing a rare case of HPV-related oropharyngeal carcinoma (OPC) with the combined histology of SmCC and SqCC. Immunohistochemical analysis and HPV-RNA in situ hybridization (ISH) suggested that both SmCC and SqCC were HPV-related malignancies. Targeted exome sequencing revealed that SmCC and SqCC had no significant difference in mutations of known driver genes. In contrast, RNA sequencing followed by bioinformatic analyses suggested that aberrant transcriptional programs may be responsible for the neuroendocrine differentiation of HPV-related OPC. Compared to SqCC, genes upregulated in SmCC were functionally enriched in inflammatory and immune responses (e.g., arachidonic acid metabolism). We then developed a SmCC-like gene module (top 10 upregulated genes) and found that OPC patients with high module activity showed poor prognosis in The Cancer Genome Atlas (TCGA) and GSE65858 cohort. Gene set enrichment analysis of the SmCC-like gene module suggested its link to MYC proto-oncogene in the TCGA dataset. Taken together, these findings suggest that the SmCC-like gene module may contribute to acquisition of aggressive phenotypes and tumor heterogeneity of HPV-related OPC. The present case study is the first report of genetic and transcriptomic aberrations in HPV-related OPSmCC combined with SqCC.

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“…Many members of the kallikrein-related peptidase family, which encompasses 15 closely related serine proteases [ 9 ], are dysregulated and implicated in biologically relevant processes in various cancer types, including ovarian, breast, and prostate cancer [ 10 ]. Several KLKs are expressed in normal breast tissue, and most of them (KLK4–8 and KLK12) have been recognized as potential diagnostic and/or prognostic markers in breast cancer, particularly in TNBC [ 11 , 12 , 13 , 14 , 15 ]. Moreover, the dysregulated expression pattern of distinct KLKs during carcinogenesis strongly points towards a functional role of these proteases for breast cancer progression.…”

Section: Introductionmentioning

confidence: 99%

A Pair of Prognostic Biomarkers in Triple-Negative Breast Cancer: KLK10 and KLK11 mRNA Expression

Liu

Gong

Preis

et al. 2022

Life

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Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with poor patient prognosis and limited therapeutic options. A lack of prognostic biomarkers and therapeutic targets fuels the need for new approaches to tackle this severe disease. Extracellular matrix degradation, release, and modulation of the activity of growth factors/cytokines/chemokines, and the initiation of signaling pathways by extracellular proteolytic networks, have been identified as major processes in the carcinogenesis of breast cancer. Members of the kallikrein-related peptidase (KLK) family contribute to these tumor-relevant processes, and are associated with breast cancer progression and metastasis. In this study, the clinical relevance of mRNA expression of two members of this family, KLK10 and KLK11, has been evaluated in TNBC. For this, their expression levels were quantified in tumor tissue of a large, well-characterized patient cohort (n = 123) via qPCR. Although, in general, the overall expression of both factors are lower in tumor tissue of breast cancer patients (encompassing all subtypes) compared to normal tissue of healthy donors, in the TNBC subtype, expression is even increased. In our cohort, a significant, positive correlation between the expression levels of both KLKs was detected, indicating a coordinate expression mode of these proteases. Elevated KLK10 and KLK11 mRNA levels were associated with poor patient prognosis. Moreover, both factors were found to be independent of other established clinical factors such as age, lymph node status, or residual tumor mass, as determined by multivariable Cox regression analysis. Thus, both proteases, KLK10 and KLK11, may represent unfavorable prognostic factors for TNBC patients and, furthermore, appear as promising potential targets for therapy in TNBC.

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Prognostic value of kallikrein-related peptidase 12 (KLK12) mRNA expression in triple-negative breast cancer patients

Cited by 10 publications

References 46 publications

Depicting the Implication of miR-378a in Cancers

Depicting the Implication of miR-378a in Cancers

Genetic and transcriptomic analyses in a rare case of human papillomavirus–related oropharyngeal squamous-cell carcinoma combined with small-cell carcinoma

A Pair of Prognostic Biomarkers in Triple-Negative Breast Cancer: KLK10 and KLK11 mRNA Expression

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