CD44v9 as a poor prognostic factor of triple-negative breast cancer treated with neoadjuvant chemotherapy

Tokunaga, Eriko; Fujita, Akio; Takizawa, Kenji; Baba, Kimiko; Akiyoshi, Sayuri; Nakamura, Yoshiaki; Ijichi, Hideki; Masuda, Takanobu; Koga, Chinami; Tajiri, Wakako; Ohno, Shinji; Taguchi, Kenichi; Ishida, M.

doi:10.1007/s12282-018-0888-y

Cited by 9 publications

(15 citation statements)

References 32 publications

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“…Regarding to countries, 10 studies were conducted in Japan, [ 17 , 20 – 25 , 27 , 30 , 31 ] 2 studies in China, [ 26 , 29 ] 1 study in Austria, [ 18 ] 1 study in Korea, [ 19 ] and 1 study in India. [ 28 ] With respect to types of cancer, 11 types of cancer were investigated, including head and neck cancer, [ 17 ] multiple myeloma, [ 18 ] gastric cancer, [ 19 , 21 , 25 , 31 ] upper tract urothelial cancer, [ 20 ] hepatocellular carcinoma, [ 22 ] colorectal cancer, [ 23 ] bladder cancer, [ 24 ] pancreatic cancer, [ 26 ] gallbladder cancer, [ 27 ] breast cancer, [ 28 , 30 ] and laryngeal cancer. [ 29 ] Besides, 11 studies reported the clinical stage of patients, [ 17 , 19 , 20 , 22 , 23 , 25 , 26 , 28 – 31 ] while 4 studies did not report the information about the clinical stage.…”

Section: Resultsmentioning

confidence: 99%

“…[ 23 , 26 – 28 ] As for clinical outcomes, 12 studies reported clinicopathological parameters, [ 18 – 26 , 28 , 29 , 31 ] 6 studies reported OS, [ 18 , 19 , 22 , 23 , 26 , 27 ] 2 studies reported DSS, [ 17 , 25 ] 2 studies reported CSS, [ 20 , 24 ] 4 studies reported RFS, [ 20 – 22 , 31 ] 1 study reported PFS [ 24 ] and 1 study reported DMFS. [ 30 ] Additionally, regarding to the analysis model of survival, 7 studies used the multivariate analysis model [ 17 , 18 , 20 , 22 , 23 , 25 , 26 ] and 3 studies used the univariate analysis model. [ 19 , 24 , 27 ] NOS score was ≥6 in all studies, which suggested that all studies were with relatively high quality.…”

Section: Resultsmentioning

confidence: 99%

“…4 , 4 studies reported RFS, [ 20 – 22 , 31 ] 1 study reported PFS, [ 24 ] and 1 study reported DMFS. [ 30 ] Compared with negative CD44v9 expression, positive CD44v9 expression was obviously associated with shorter RFS (HR = 3.60, 95% CI, 1.52–8.53, P < .01; I 2 = 82%, P heterogeneity < .01) and PFS (HR = 3.35, 95% CI, 1.08–10.40, P = .04; I 2 = 76%, P heterogeneity = .04). However, no distinct relationship between CD44v9 expression and DMFS was observed (HR = 2.23, 95% CI, 0.22–22.60, P = .50).…”

Section: Resultsmentioning

confidence: 99%

“…Many publications have explored the underlying mechanisms of prognostic significance of CD44v9 expression in cancers. [ 19 , 22 , 24 , 25 , 30 , 34 , 35 ] Yamakawa et al [ 34 ] found CD44v9 might enhance pentose phosphate pathway flux and maintain glutathione levels in gastric cancer cell. Kobayashi et al [ 24 ] discovered CD44v9 promoted the tumor invasion and induced the worse prognosis via epithelial-mesenchymal transition in bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

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Prognostic value of CD44v9 expression in human cancers: Retraction

Zeng¹,

Chen

et al. 2020

Medicine

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Background: The prognostic significance of CD44 variant-9 (CD44v9) expression in human cancers has been investigated in several studies, however, definite conclusion has not be reached. The aim of this systematic review and meta-analysis was to evaluate the prognostic significance of CD44v9 expression in various cancers. Methods: Three common databases were searched and retrieved studies were assessed using the inclusion and exclusion criteria. The further analyses for overall survival (OS), recurrence-free survival (RFS), and clinicopathological parameters were performed. Results: Fifteen studies containing 1633 cancer patients were included into this research. Patients with positive CD44v9 expression tended to have shorter OS (hazard ratio [HR] = 1.93, 95% confidence interval [CI] = 1.48–2.52, P < .01) and RFS (HR = 3.60, 95% CI = 1.52–8.53, P < .01) when compared with patients with negative CD44v9 expression. Positive CD44v9 expression was associated with larger tumor size ( P = .04), deeper tumor invasion ( P < .01), earlier lymph node metastasis ( P < .01), and more advanced clinical stage ( P < .01) when compared with negative CD44v9 expression. Conclusion: Positive CD44v9 expression predicted worse prognosis in human cancers compared with negative CD44v9 expression. CD44v9 expression could serve as a prognostic factor of human cancers.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Prognostic value of CD44v9 expression in human cancers: Retraction

Zeng¹,

Chen

et al. 2020

Medicine

View full text Add to dashboard Cite

show abstract

“…The CD44v9 + group had a poor prognosis for hepatocellular carcinoma, breast cancer, plasmacytoma, gastric cancer, bladder cancer, gallbladder cancer and ICC (15,21,(30)(31)(32)(33). There was, however, no signi cant difference in the PFS and OS between the CD44v9 + and CD44v9 − groups by the Kaplan-Meier method (log-rank test) and Cox proportional hazards model in the present study (Tables 3 & 4, Fig.…”

Section: Discussionmentioning

confidence: 44%

Cancer stem cell marker-positive tumour nests in intrahepatic cholangiocarcinoma are related to epithelial type CD1a-positive dendritic cell infiltration and to high Sox9 expression

Utsunomiya

Ohe²,

Kabasawa³

et al. 2020

Preprint

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Background It is yet a mystery whether dendritic cells (DCs) contact cancer stem cells (CSCs) and uptake CSC antigens in intrahepatic cholangiocarcinoma (ICC). The aim of this study was to examine the histological relationship between tumour cells expressing CSC markers and DCs infiltrating ICC. In addition, clinicopathological factors, including progression-free survival (PFS) and overall survival (OS), were compared between cases with many and few CSC marker-positive cells. Materials and methods Resected tissue sections of 22 cases with ICC were used for immunostaining to detect DC infiltration into ICC tumour nests positive for CD1a, DC-SIGN, DEC205, DC-LAMP, and CD123 and to detect ICC tumour cells positive for CSC markers such as CD44v9, EpCAM, and Sox9. The relationship between the number of CSC marker-positive cells and ICC clinicopathological factors was examined by Kaplan-Meier method and univariate and multivariate analyses using the Cox proportional hazards model. Results CD1a+ immature DCs infiltrated ICC tumour nests significantly more than the other types of DCs. Furthermore, they were frequently localized within CD44v9− and EpCAMhigh ICC tumour nests. According to Kaplan-Meier method, PFS and OS were longer in the Sox9high group than in the Sox9low group, and according to both univariate and multivariate analyses, Sox9 expression was an independent factor. Conclusion The present study first demonstrated that CD1a+ immature DCs frequently infiltrated CD44v9− and EpCAMhigh ICC tumour nests, suggesting the possibility of cell-to-cell contact between epithelial type immature DCs and CSCs in ICC. Furthermore, it was suggested that Sox9 expression in ICC may be a prognostic factor.

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TDP43 promotes stemness of breast cancer stem cells through CD44 variant splicing isoforms

et al. 2022

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Alternative splicing (AS) is a promising clinical target for cancer treatment at the post-transcriptional level. We previously identified a unique AS profile in triple-negative breast cancer (TNBC), which is regulated by the splicing regulator TAR DNA-binding protein-43 (TDP43), thus indicating the crucial role of TDP43 in heterogeneous TNBC. Cluster of differentiation 44 (CD44), a widely recognized marker for breast cancer stem cells (BCSCs), is extensively spliced into CD44 variant AS isoforms (CD44v) during the development of breast cancer. At present, however, the regulatory mechanism of CD44v is not fully understood. In the current study, we found that loss of TDP43 inhibits BCSC stemness by reducing the abundance of CD44v. In addition, serine-arginine-rich splicing factor 3 (SRSF3), another splicing factor and partner of TDP43, acts as an upstream regulator of TDP43 to maintain CD44v isoforms and thereafter BCSC stemness. Mechanistically, SRSF3 stabilizes the mRNA of TDP43 by inhibiting nonsense-mediated decay (NMD). These findings illustrate the important role of complicated regulatory networks formed by splicing factors in TNBC progression, thus providing potential therapeutic targets from an AS perspective.

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CD44v9 as a poor prognostic factor of triple-negative breast cancer treated with neoadjuvant chemotherapy

Abstract: High CD44v9 expression in pre-NAC samples was associated with poor prognosis in TNBC patients treated with NAC, especially for those in whom pCR was not achieved.

Cited by 9 publications

References 32 publications

Prognostic value of CD44v9 expression in human cancers: Retraction

Prognostic value of CD44v9 expression in human cancers: Retraction

Cancer stem cell marker-positive tumour nests in intrahepatic cholangiocarcinoma are related to epithelial type CD1a-positive dendritic cell infiltration and to high Sox9 expression

TDP43 promotes stemness of breast cancer stem cells through CD44 variant splicing isoforms

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