Piwi-like 1 and -2 protein expression levels are prognostic factors for muscle invasive urothelial bladder cancer patients

Eckstein, Markus; Jung, Rudolf; Weigelt, Katrin; Sikic, Danijel; Stöhr, Robert; Geppert, Carol I.; Agaimy, Abbas; Lieb, Verena; Hartmann, Arndt; Wullich, Bernd; Wach, Sven; Täubert, Helge

doi:10.1038/s41598-018-35637-4

Cited by 18 publications

(14 citation statements)

References 47 publications

(57 reference statements)

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“…Consistent with the proposed tumor-promoting role of PIWL1 during tumorigenesis and tumor progression, PIWIL1 can be overexpressed in many different types of tumor (Table 1), including gastric cancer (Liu et al, 2006;Wang et al, 2012;Gao et al, 2018), softtissue sarcoma (Taubert et al, 2007), esophageal squamous cell carcinoma (He et al, 2009), endometrial cancer (Liu et al, 2010b), colon cancer Litwin et al, 2015;Wang H.L. et al, 2015;Sun et al, 2017), cervical cancer (Li S. et al, 2010;Liu et al, 2010a), glioma (Sun et al, 2011), hepatocellular carcinoma (Jiang et al, 2011;Zhao et al, 2012), ovarian cancer (Li S. et al, 2010;Chen et al, 2013), breast cancer (Li S. et al, 2010;Wang D.W. et al, 2014;Cao et al, 2016;Litwin et al, 2018), bladder cancer (Eckstein et al, 2018), and renal cell carcinoma (Stöhr et al, 2019). However, real-time PCR analysis of renal cell carcinoma and non-tumor renal parenchyma tissues found a significant downregulation of PIWIL1 in renal cell carcinoma tissues (Iliev et al, 2016).…”

Section: Dysregulation Of Piwil1 In Tumormentioning

confidence: 99%

Critical Roles of PIWIL1 in Human Tumors: Expression, Functions, Mechanisms, and Potential Clinical Implications

Dong

Xiong

Konno

et al. 2021

Front. Cell Dev. Biol.

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P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a class of small non-coding RNA molecules that are 24–31 nucleotides in length. PiRNAs are thought to bind to PIWI proteins (PIWL1-4, a subfamily of Argonaute proteins), forming piRNA/PIWI complexes that influence gene expression at the transcriptional or post-transcriptional levels. However, it has been recently reported that the interaction of PIWI proteins with piRNAs does not encompass the entire function of PIWI proteins in human tumor cells. PIWIL1 (also called HIWI) is specifically expressed in the testis but not in other normal tissues. In tumor tissues, PIWIL1 is frequently overexpressed in tumor tissues compared with normal tissues. Its high expression is closely correlated with adverse clinicopathological features and shorter patient survival. Upregulation of PIWIL1 drastically induces tumor cell proliferation, epithelial-mesenchymal transition (EMT), invasion, cancer stem-like properties, tumorigenesis, metastasis and chemoresistance, probably via piRNA-independent mechanisms. In this article, we summarize the current existing literature on PIWIL1 in human tumors, including its expression, biological functions and regulatory mechanisms, providing new insights into how the dysregulation of PIWIL1 contributes to tumor initiation, development and chemoresistance through diverse signaling pathways. We also discuss the most recent findings on the potential clinical applications of PIWIL1 in cancer diagnosis and treatment.

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Section: Dysregulation Of Piwil1 In Tumormentioning

confidence: 99%

Critical Roles of PIWIL1 in Human Tumors: Expression, Functions, Mechanisms, and Potential Clinical Implications

Dong

Xiong

Konno

et al. 2021

Front. Cell Dev. Biol.

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“…PIWI-like 2 correlated with recurrence-free survival. Both proteins showed prognostic significance in bladder cancer subtypes [ 26 ]. PIWI-like 1 protein expression correlated with decreased cancer-specific survival, grading, tumor stage and distant metastases in renal cell carcinoma [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

PIWI-Like 1 and PIWI-Like 2 Expression in Breast Cancer

Erber

Meyer

Täubert

et al. 2020

Cancers

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PIWI-like 1 and PIWI-like 2 play a role in stem cell self-renewal, and enhanced expression has been reported for several tumor entities. However, few studies have investigated PIWI-like 1 and PIWI-like 2 expressions in breast cancer subtypes regarding prognosis. Therefore, we examined protein expression in a large consecutive cohort of breast cancer patients and correlated it to breast cancer subtypes and survival outcome. PIWI-like 1 and PIWI-like 2 expressions were evaluated using immunohistochemistry in a cohort of 894 breast cancer patients, of whom 363 were eligible for further analysis. Percentage and intensity of stained tumor cells were analyzed and an immunoreactive score (IRS) was calculated. The interaction of PIWI-like 1 and PIWI-like 2 showed a prognostic effect on survival. For the combination of high PIWI-like 1 and low PIWI-like 2 expressions, adjusted hazard ratios (HRs) were significantly higher with regard to overall survival (OS) (HR 2.92; 95% confidence interval (CI) 1.24, 6.90), disease-free survival (DFS) (HR 3.27; 95% CI 1.48, 7.20), and distant disease-free survival (DDFS) (HR 7.64; 95% CI 2.35, 24.82). Both proteins were significantly associated with molecular-like and PAM50 subgroups. Combining high PIWI-like 1 and low PIWI-like 2 expressions predicted poorer prognosis and both markers were associated with aggressive molecular subtypes.

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“…Ten randomly picked view fields from each slide were assessed. The staining intensity and proportion of positively stained cells were evaluated as described previously with minor modifications [7]. The intensity of Rab43 staining (brown color) was scored as follows: 0, negative; 1, weak; 2, moderate; 3, strong; And the percentage of positively stained cells was scored as follows: 0, < 5%; 1, 5–25%; 2, 26–50%; 3, 51–75%; 4, > 75%.…”

Section: Methodsmentioning

confidence: 99%

A germline mutation in Rab43 gene identified from a cancer family predisposes to a hereditary liver-colon cancer syndrome

Jiang

Sun

et al. 2019

BMC Cancer

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Background Hereditary cancer syndromes have inherited germline mutations which predispose to benign and malignant tumors. Understanding of the molecular causes in hereditary cancer syndromes has advanced cancer treatment and prevention. However, the causal genes of many hereditary cancer syndromes remain unknown due to their rare frequency of mutation. Methods A large Chinese family with a history of hereditary liver-colon cancer syndrome was studied. The genomic DNA was extracted from the blood samples of involved family members, whole-exome sequencing was performed to identify genetic variants. Functional validation of a candidate variant was carried out using gene expression, gene knockout and immunohistochemistry. Results The whole-exome of the proband diagnosed with colon cancer was sequenced in comparison with his mother. A total of 13 SNVs and 16 InDels were identified. Among these variants, we focused on a mutation of Rab43 gene, a GTPase family member involving in protein trafficking, for further validation. Sanger DNA sequencing confirmed a mutation (c: 128810106C > T, p: A158T) occurred in one allele of Rab43 gene from the proband, that heterozygous mutation also was verified in the genome of the proband’s deceased father with liver cancer, but not in his healthy mother and sister. Ectopic expression of the Rab43 A158T mutant in Huh7 cells led to more enhanced cell growth, proliferation and migration compared to the expression of wild type Rab43. Conversely, knockout of Rab43 in HepG2 cells resulted in slow cell growth and multiple nuclei formation and impaired activation of Akt. Finally, a positive correlation between the expression levels of Rab43 protein and cancer development in that family was confirmed. Conclusions A germline mutation of Rab43 gene is identified to be associated with the onset of a familial liver-colon cancer syndrome. Our finding points to a potential role of protein trafficking in the tumorigenesis of the familial cancer syndrome, and helps the genetic counseling to the affected family members. Electronic supplementary material The online version of this article (10.1186/s12885-019-5845-4) contains supplementary material, which is available to authorized users.

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Piwi-like 1 and -2 protein expression levels are prognostic factors for muscle invasive urothelial bladder cancer patients

Cited by 18 publications

References 47 publications

Critical Roles of PIWIL1 in Human Tumors: Expression, Functions, Mechanisms, and Potential Clinical Implications

Critical Roles of PIWIL1 in Human Tumors: Expression, Functions, Mechanisms, and Potential Clinical Implications

PIWI-Like 1 and PIWI-Like 2 Expression in Breast Cancer

A germline mutation in Rab43 gene identified from a cancer family predisposes to a hereditary liver-colon cancer syndrome

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