High expression of p63 is correlated to poor prognosis in squamous cell carcinoma of the tongue

Loljung, Lotta; Coates, Philip J.; Nekulova, Marta; Laurell, Göran; Wahlgren, Magnus; Wilms, Torben; Widlöf, Mikael; Hansel, Anna; Nylander, Karin

doi:10.1111/jop.12074

Cited by 19 publications

(17 citation statements)

References 29 publications

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“…Although some studies had reported an influence of p63 expression in clinical–pathological characteristics (Lo Muzio et al , ; de Oliveira et al , ; Moergel et al , ; Loljung et al , ), we could not find any relationship of p63 with these parameters in our sample. This was true even on survival analysis.…”

Section: Discussioncontrasting

confidence: 75%

“…This was true even on survival analysis. This result is not unexpected as many studies had reported conflicting results on p63 expression in survival analysis using IHC (Lo Muzio et al , ; de Oliveira et al , ; Moergel et al , ; Loljung et al , ). These discrepancies could be related to the different functions of p63 isoforms perhaps in different tumours locations.…”

Section: Discussionmentioning

confidence: 61%

“…In cancer cells, p63 promotes cell proliferation and survival, being considered important for self‐renewal of cancer cells suggesting that this protein acts as a cancer stem cell (CSC) marker (Nylander et al , ). Overexpression of p63 has been found in several cancers including lung, skin, cervix and head and neck cancers and was associated with aggressiveness and prognosis (de Oliveira et al , ; Romano et al , ; Loljung et al , ).…”

Section: Introductionmentioning

confidence: 99%

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Prognostic significance of CD44v6, p63, podoplanin and MMP‐9 in oral squamous cell carcinomas

et al. 2016

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Section: Discussioncontrasting

confidence: 75%

Section: Discussionmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 99%

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Prognostic significance of CD44v6, p63, podoplanin and MMP‐9 in oral squamous cell carcinomas

et al. 2016

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“…The dysregulation of TP63 has been reported in various human malignancies and its overexpression is closely associated with clinical outcomes [18, 19, 37, 38]. Generally, OSCC patients with elevated TP63 levels have a poorer survival rate.…”

Section: Discussionmentioning

confidence: 99%

Interplay between ΔNp63 and miR-138-5p regulates growth, metastasis and stemness of oral squamous cell carcinoma

Zhuang

Xie²,

et al. 2017

Oncotarget

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TP63 acts as a master regulator in epithelia development and in the progression of various cancers, but its role in oral cancer pathogenesis remains unknown. This study aimed to explore the role of TP63 in the progression of oral squamous cell carcinoma (OSCC). This study shows that ΔNp63, the predominant isoform of TP63, is significantly upregulated in OSCC tissues and cell lines compared with their normal counterparts, and its expression is closely correlated with pathological differentiation, lymph node metastasis and clinical stage in patients with OSCC. The overexpression of ΔNp63 promotes growth, metastasis and stem-like properties in OSCC cells, and ΔNp63 depletion significantly represses OSCC cellular phenotypes in vitro and in vivo. The ΔNp63 isoform transcriptionally suppresses miR-138-5p expression; restoration of miR-138-5p expression partially abolishes the effect of upregulating ΔNp63. This study also demonstrates that miR-138-5p directly targets ΔNp63, resulting in crosstalk with ΔNp63. The correlation between ΔNp63 and miR-138-5p was further validated in OSCC tissues and was found to be significantly associated with the prognosis of patients with OSCC. Therefore, our data reveal that the interplay between ΔNp63 and miR-138-5p promotes OSCC progression by regulating cell growth, metastasis and stemness.

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“…Several studies have documented a link between the aberrant expression of TAp63 (22) and the pathogenesis/prognosis in several types of cancer (23,24). However, thus far, the expression and clinical significance of TAp63 in colorectal cancer (CRC) have not been explored.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-133b is regulated by TAp63 while no gene mutation is present in colorectal cancer

Chen

Zhang

et al. 2017

Oncology Reports

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Downregulation of miR-133b has been reported in multiple types of malignancies including colorectal cancer (CRC). We previously confirmed that TAp63 actively translates microRNA-133b (miR-133b) transcripts. While the presence of miRNA mutations have frequently been described in CRC, most CRCs do not show any variation in the miR‑133b coding sequence. Therefore, it is important to elucidate the relationship between TAp63 and miR-133b, and identify other mediators of miR-133b downregulation in CRC. The expression of TAp63 was detected by RT-qPCR, western blotting, immunohistochemistry (IHC) and densitometric analysis using Image-Pro Plus 6.0 software in 38 CRC and corresponding non-cancerous tissues (NCTs). The expression of mature miR‑133b was determined by RT-qPCR, in situ hybridization (ISH) and densitometric analysis using Image-Pro Plus 6.0 software. The DNA from 38 CRC tissues and NCTs were screened for miR-133b mutations through sequence analysis. Compared with the NCTs, TAp63 mRNA expression was significantly lower in 21 (55.27%) tumor tissues. Compared with the NCTs, the miR‑133b expression level was significantly lower in 31 (81.58%) tumor tissues. The expression of miR‑133b was found to be positively correlated with TAp63. Loss of TAp63 and miR-133b was associated with an increased likelihood of metastatic events. The area under the ROC curve (AUC) of TAp63 for CRC was 0.623 [95% confidence interval (CI), 0.497-0.748; P=0.046], with 73.7% sensitivity and 50% specificity, respectively. The AUC of miR-133b for CRC was 0.857 (95% CI, 0.774‑0.940; P<0.0001), with 78.9% sensitivity and 81.6% specificity, respectively. The combined AUC of TAp63 and miR-133b for CRC was 0.881 (95% CI, 0.805-0.956; P<0.0001), with 89.5% sensitivity and 71.1% specificity, respectively. Point mutations within the seed region of miR-133b were found in 1 patient, but the point mutation did not impact the secondary structure of the pre-miR-133b. Therefore, downregulation of TAp63 may be one reason for the dysregulation of miR‑133b in CRC. The expression analysis of TAp63 and miR-133b revealed that they may be used as valuable prognostic biomarkers for CRC.

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High expression of p63 is correlated to poor prognosis in squamous cell carcinoma of the tongue

Abstract: Based on the present data, we recommend using expression of p63 as an additional factor contributing prognostic information in analysis of SCC in the tongue.

Cited by 19 publications

References 29 publications

Prognostic significance of CD44v6, p63, podoplanin and MMP‐9 in oral squamous cell carcinomas

Prognostic significance of CD44v6, p63, podoplanin and MMP‐9 in oral squamous cell carcinomas

Interplay between ΔNp63 and miR-138-5p regulates growth, metastasis and stemness of oral squamous cell carcinoma

MicroRNA-133b is regulated by TAp63 while no gene mutation is present in colorectal cancer

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