KRT17 as a prognostic biomarker for stage II colorectal cancer

Ujiie, Daisuke; Okayama, Hirokazu; Saito, Katsuharu; Ashizawa, Mai; Min, Aung Kyi Thar; Endo, Eisei; Kase, Koji; Yamada, Leo; Kikuchi, Tomohiro; Hanayama, Hiroyuki; Fujita, Shotaro; Sakamoto, Wataru; Endo, Hisahito; Saito, Motonobu; Mimura, Kosaku; Saze, Zenichiro; Momma, Tomoyuki; Ohki, Shinji; Kono, Koji

doi:10.1093/carcin/bgz192

Cited by 29 publications

(34 citation statements)

References 44 publications

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“…Keratin KRT17, belonging to type I keratin, was regenerated and highly expressed in many cancers [ 38 ], including gastric cancer [ 39 ], cervical cancer [ 40 ], oral squamous cell carcinoma [ 41 ], and breast cancer [ 42 ]. Moreover, KRT17 expression was proposed as a prognostic marker that can discriminate postoperative stage II patients with colorectal cancer with a high probability of disease recurrence, as support to available risk stratification factors [ 43 ]. Extracellular matrix protein 1 (ECM1), in turn, is a glycoprotein involved in cell proliferation, angiogenesis, migration, and metastases.…”

Section: Discussionmentioning

confidence: 99%

TERT Promoter Mutations and Their Impact on Gene Expression Profile in Papillary Thyroid Carcinoma

Rusinek

Pfeifer

Cieślicka

et al. 2020

Cancers

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Background: Telomerase reverse transcriptase promoter (TERTp) mutations are related to a worse prognosis in various malignancies, including papillary thyroid carcinoma (PTC). Since mechanisms responsible for the poorer outcome of TERTp(+) patients are still unknown, searching for molecular consequences of TERTp mutations in PTC was the aim of our study. Methods: The studied cohort consisted of 54 PTCs, among them 24 cases with distant metastases. BRAF V600E, RAS, and TERTp mutational status was evaluated in all cases. Differences in gene expression profile between TERTp(+) and TERTp(−) PTCs were examined using microarrays. The evaluation of signaling pathways and gene ontology was based on the Gene Set Enrichment Analysis. Results: Fifty-nine percent (32/54) of analyzed PTCs were positive for at least one mutation: 27 were BRAF(+), among them eight were TERTp(+), and 1 NRAS(+), whereas five other samples harbored RAS mutations. Expression of four genes significantly differed in BRAF(+)TERTp(+) and BRAF(+)TERTp(−) PTCs. Deregulation of pathways involved in key cell processes was observed. Conclusions: TERTp mutations are related to higher PTC aggressiveness. CRABP2 gene was validated as associated with TERTp mutations. However, its potential use in diagnostics or risk stratification in PTC patients needs further studies.

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Section: Discussionmentioning

confidence: 99%

TERT Promoter Mutations and Their Impact on Gene Expression Profile in Papillary Thyroid Carcinoma

Rusinek

Pfeifer

Cieślicka

et al. 2020

Cancers

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“…The tumors with a score of 0 or 1 were classified as TIPE1 low-expression tumors, while those with a score of 2–4 were classified as TIPE1 high-expression tumors. The analysis of the association between TIPE1 expression and patient prognosis was performed as previously described ( 20 ).…”

Section: Methodsmentioning

confidence: 99%

TIPE1 impairs ovarian tumor growth by promoting caspase-dependent apoptosis

Deng

et al. 2020

Oncol Lett

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Tumor necrosis factor-α-induced protein 8-like 1 (TIPE1) functions as a tumor suppressor in several types of cancer, including lung and breast cancer. The present study aimed to determine the level of expression and the function of TIPE1 in ovarian cancer. TIPE1 expression was determined in tissue microarrays and ovarian cancer cells, and these data were analyzed to assess the association between TIPE1 expression and prognosis in patients with ovarian cancer. The potential antitumor effects of TIPE1 were investigated in vitro and in a xenograft mouse model. Furthermore, the underlying molecular mechanism by which TIPE1 regulates ovarian cancer growth was determined via flow cytometric analysis, western blotting and rescue experiments. The results of the present study indicated that TIPE1 levels were markedly decreased in ovarian cancer tissues, and its level of expression was associated with a favorable prognosis of patients with ovarian cancer. In addition, ectopic TIPE1 expression significantly impaired A2780 and SKOV3 cell proliferation and colony formation in vitro , which was accompanied by efficient inhibition of xenograft tumor growth in mice. Investigations into the underlying molecular mechanism demonstrated that TIPE1 induced ovarian cancer cell apoptosis by promoting caspase protein expression. Inhibition of caspase-dependent apoptosis by z-VAD blocked TIPE1-mediated inhibition of the proliferation and induction of apoptosis in ovarian cancer cells. Collectively, the results of the present study suggest that TIPE1 may be a potential prognostic predictor and therapeutic target for patients with ovarian cancer.

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“…GC cell lines were obtained from the American Type Culture Collection (Manassas, VA, USA) and RIKEN BioResource Center (Ibaraki, Japan). These cells lines were authenticated by short tandem repeat analysis in April 2020 (Promega) [21]. Cells were cultured in RPMI-1640 medium (Sigma-Aldrich; Merck KGaA, Darmstadt, Germany).…”

Section: Cell Culturementioning

confidence: 99%

Selective sensitivity of EZH2 inhibitors based on synthetic lethality in ARID1A-deficient gastric cancer

et al. 2020

Self Cite

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Background AT-rich interactive domain 1A (ARID1A) is a tumor suppressor gene that is frequently mutated in gastric cancer (GC). Although ARID1A mutations are not a druggable target for conventional treatments, novel therapeutic strategies based on a synthetic lethal approach are effective for ARID1A-deficient cancers. The histone methyltransferase EZH2 acts in a synthetic lethal manner in ARID1A-mutated ovarian cancer, although its role in GC remains unknown. Methods The selective sensitivity of the EZH2 inhibitors for ARID1A-deficient GC cells was evaluated using cell viability and colony formation assays. The expression of PI3K/AKT signaling genes were investigated using TCGA's cBioPortal database to determine whether the homeostasis between ARID1A and EZH2 is related to cell proliferation and survival via the PI3K/AKT signaling pathway. We also evaluated the phosphorylation of PI3K/AKT signaling proteins in ARID1A knock downed ARID1A-WT GC cells. Results EZH2 inhibitors decreased the viability of ARID1A-deficient cells in a dose-dependent manner and demonstrated the selective sensitivity to ARID1A-deficient cells in vitro experiment system. Bioinformatics approach revealed that the PI3K/AKT signaling was tended to be activated in ARID1A-deficient GC enhancing cell viability and, furthermore, downregulation of EZH2 in ARID1A-deficient GC was related to normalization of PI3K/AKT signaling pathway. The cell experiment revealed that phosphorylated AKT was upregulated in ARID1A-deficent GC cells. Conclusions The present findings provide a rationale for the selective sensitivity of EZH2 inhibitors against ARID1Adeficient GC and suggest the potential efficacy of targeted therapy using EZH2 inhibitors in this patient population.

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KRT17 as a prognostic biomarker for stage II colorectal cancer

Cited by 29 publications

References 44 publications

TERT Promoter Mutations and Their Impact on Gene Expression Profile in Papillary Thyroid Carcinoma

TERT Promoter Mutations and Their Impact on Gene Expression Profile in Papillary Thyroid Carcinoma

TIPE1 impairs ovarian tumor growth by promoting caspase-dependent apoptosis

Selective sensitivity of EZH2 inhibitors based on synthetic lethality in ARID1A-deficient gastric cancer

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