Loss of ASRGL1 expression is an independent biomarker for disease-specific survival in endometrioid endometrial carcinoma

Edqvist, Per‐Henrik; Huvila, Jutta; Talve, Lauri; Carpén, Olli; Salvesen, Helga B.; Krakstad, Camilla; Grénman, Seija; Johannesson, Henrik; Ljungqvist, Oscar; Uhlén, Mathias; Pontén, Fredrik; Auranen, Annika

doi:10.1016/j.ygyno.2015.03.055

Cited by 24 publications

(28 citation statements)

References 33 publications

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“…To profile a range of biological functions including metabolism, enzyme ‘Asparaginase-Like 1’ (ASRGL1; aka ALP1) was chosen for immunofluorescence analysis. ASRGL1 is known to catalyze the hydrolysis of L-asparagine 40 and to clear protein-damaging isoaspartyl-peptides 41 , and while largely uncharacterized in the mouse, has been found to be highly expressed in the human cervix, fallopian tube, ovary, and testis 42 . Interestingly, ASRGL1 has been identified as a biomarker of endometrial cancer 42–45 , as well as an antigen in rodent sperm 46 .…”

Section: Resultsmentioning

confidence: 99%

Dynamic transcriptome profiles within spermatogonial and spermatocyte populations during postnatal testis maturation revealed by single-cell sequencing

Grive

Shu

et al. 2018

Preprint

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21Spermatogenesis is the process by which male gametes are formed from a self-22 high-resolution, single-cell depth. Not only does this analysis reveal previously unknown 44 transcriptional dynamics of a highly transitional cell population, it has also begun to 45 reveal critical differences in biological pathway utilization in developing spermatogonia 46 and spermatocytes, including response to DNA damage and double-strand breaks. 47 48 Author Summary 49Spermatogenesis is the process by which male gametes -mature spermatozoa 50 -are produced in the testis. This process requires exquisite control over many 51 developmental transitions, including the self-renewal of the germline stem cell 52 population, commitment to meiosis, and ultimately, spermiogenesis. While much is 53 known about molecular mechanisms regulating single transitions at single time points in 54 the mouse, much less is understood about how the spermatogenic progenitor cells, 55 spermatogonia, or the meiotic cells, spermatocytes, of the testis change over 56 developmental age. 57Our single-cell-mRNA-sequencing analysis is the first to profile both 58 spermatogonia and spermatocytes from neonatal mice through adulthood, revealing 59 novel gene expression dynamics and differential utilization of biological pathways. 60These discoveries help us to understand how the spermatogenic progenitors of this 61 population modulate their activity to adapt to a changing testicular environment. 62 Furthermore, they also begin to explain previously-observed differences -and 63 deficiencies -in spermatocytes that are derived from the first "wave" of 64 spermatogenesis. Overall, this dataset is the first of its kind to comprehensively profile 65 4 gene expression dynamics in male germ cell populations over time, enriching our 66 understanding of the complex and highly-orchestrated process of spermatogenesis. 67 68 Introduction 69 Mammalian spermatogenesis requires proper establishment of the 70 spermatogonial stem cell (SSC) pool, which resides within the seminiferous tubules of 71 testis and supports life-long germ cell development 1 . These progenitors give rise to all 72the differentiating germ cells of the mouse testis, ranging from spermatogonia to 73 spermatocytes to spermatids, and finally to mature spermatozoa. Despite the essential 74 nature of this process, the genetic regulatory mechanisms underlying the many complex 75 cellular transitions, and the maturation of this system during testis development, have 76 yet to be fully described. 77Gamete development in the mouse relies on a rare population of primordial germ 78 cells, the bi-potential progenitors of all gametes, which are specified in the developing 79 embryo at embryonic day (E) 6.25 2 . These cells migrate to and colonize the developing 80 gonad, arriving at the genital ridge from E10.5 3 , and undergo abundant proliferation 81 until E13.5. At this time, germ cells developing in an XX (female) gonad will enter the 82 meiotic program as oocytes, while germ cells developing in an XY (male) gonad w...

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Section: Resultsmentioning

confidence: 99%

Dynamic transcriptome profiles within spermatogonial and spermatocyte populations during postnatal testis maturation revealed by single-cell sequencing

Grive

Shu

et al. 2018

Preprint

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show abstract

“…Protein expression assessed by IHC staining is found to be relatively similar in curettage samples and corresponding hysterectomy specimens for several markers (concordance rates of 70–100%), suggesting that immunohistochemical evaluation of curettage specimens may aid in the identification of high‐risk cases before surgery . Loss of ASRGL1 expression in the hysterectomy specimen is found to independently predict aggressive disease and poor disease‐specific survival in women with endometrial carcinoma . Less is known about ASRGL1 expression in preoperative samples, but combined low expression of ASRGL1 and PR was recently reported to predict high FIGO stage (III–IV) among women with endometrioid endometrial carcinoma .…”

Section: Discussionmentioning

confidence: 98%

“…The optimal staining evaluation and cut‐off for ASRGL1 need to be standardised before clinical implementation. However, different methods (the staining index versus percentage of cells with positive staining) for evaluation of ASGRL1 expression have been published with very similar results, indicating that ASRGL1 might be a robust biomarker.…”

Section: Discussionmentioning

confidence: 99%

“…Slides were developed for 10 minutes with 3,3‐diaminobenzidine as substrate, before counterstaining with haematoxylin (Sigma‐Aldrich, St Louis, MO, USA). Positive ASRGL1 staining in tumour cells was scored without considering subcellular localisation, as separate analysis of nuclear and cytoplasmic signal is reported to have no additional value . For each woman, a staining index (SI) based on all three cylinders was calculated by multiplying staining intensity (range 0–3) and area of positive stained tumour cells (1 = < 10%, 2 = 10–50%, 3 = > 50%) .…”

Section: Methodsmentioning

confidence: 99%

“…High expression of ASRGL1 is reported in several tumours, including breast, ovarian and cervical cancers . In endometrial carcinoma, ASRGL1 is reported to be a strong biomarker, and loss of gene and protein expression of ASRGL1 has been found to associate with features of aggressive disease and poor survival . Still, the biological importance of ASRGL1 in normal tissues and during cancer development is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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Asparaginase‐like protein 1 expression in curettage independently predicts lymph node metastasis in endometrial carcinoma: a multicentre study

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ASRGL1: A potential therapeutic target in the treatment of hepatocellular carcinoma?

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Loss of ASRGL1 expression is an independent biomarker for disease-specific survival in endometrioid endometrial carcinoma

Cited by 24 publications

References 33 publications

Dynamic transcriptome profiles within spermatogonial and spermatocyte populations during postnatal testis maturation revealed by single-cell sequencing

Dynamic transcriptome profiles within spermatogonial and spermatocyte populations during postnatal testis maturation revealed by single-cell sequencing

Asparaginase‐like protein 1 expression in curettage independently predicts lymph node metastasis in endometrial carcinoma: a multicentre study

ASRGL1: A potential therapeutic target in the treatment of hepatocellular carcinoma?

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