Prognostic values of proliferating cell nuclear antigen (PCNA) and Ki-67 for radiotherapy of oesophageal squamous cell carcinomas

Okuno, Yoshishige; Nishimura, Yasumasa; Kashu, Ippei; Ono, Koji; Hiraoka, Masahiro

doi:10.1038/sj.bjc.6690368

Cited by 16 publications

(6 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The total cell proliferative activity was elevated by Ki-67 expression, which was strongest in the S phase, and which is observed in cell cycle phases other than G0. Generally, the CRT response cases had a high Ki-67 index, and therefore a larger population of cycling cells than cases with a low Ki-67 index (8)(9)(10)33). However, the difference was not statistically significant in our study (data not shown).…”

Section: Discussioncontrasting

confidence: 55%

“…Moreover, chemotherapy and radiotherapy are generally effective against tumor cells that have a high proliferative index. Indeed, tumors that respond best to radiation have a high Ki-67 index, a proliferation-associated marker (8)(9)(10). Furthermore, cyclinD1 overexpression is thought to accelerate the cell cycle, and is correlated with an increased cell proliferative index in esophageal cancer (11).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Expression of the prolyl isomerase Pin1 is a useful indicator of sensitivity to chemoradiotherapy in advanced esophageal squamous cell carcinoma

Fukuchi

Fukai²,

Sohda³

et al. 2009

Oncol Rep

View full text Add to dashboard Cite

Abstract. Cell cycle regulators, such as cyclinD1 and p53, play major roles in the tumor response to radiation and chemotherapy in esophageal squamous cell carcinoma (SCC). Pin1-mediated prolyl-isomerization potentiates cell cycle progression and cell proliferation, including the regulation of cyclinD1 and p53. Herein, we investigated the effect of Pin1 in association with cyclinD1 and p53 on the sensitivity of esophageal SCC to chemoradiotherapy (CRT). The expression levels of Pin1, cyclinD1 and p53 were examined immunohistochemically in endoscopic biopsy specimens from 68 advanced esophageal SCC patients before CRT to determine whether their expression levels predicted the clinical effectiveness of CRT in individual cancers. Fortysix of the 68 patients (67.6%) had an effective response to CRT, whereas 22 patients (32.4%) had an ineffective response. There was no significant correlation between clinical responses and expression levels of cyclinD1 or p53. However, the clinical response of the high Pin1 expression group was significantly higher than that of the low expression group (P=0.0200). Moreover, our data indicate that the combined immunohistochemical evaluation of Pin1, cyclinD1 and p53 expression in pretreatment biopsy samples is a useful indicator of sensitivity to CRT in advanced esophageal SCC. Thus, Pin1 may influence cyclinD1 and p53 functions and predict CRT sensitivity.

show abstract

Section: Discussioncontrasting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Expression of the prolyl isomerase Pin1 is a useful indicator of sensitivity to chemoradiotherapy in advanced esophageal squamous cell carcinoma

Fukuchi

Fukai²,

Sohda³

et al. 2009

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…For patients treated with radiotherapy, the tumors with a high Ki-67 labeling index demonstrated good local control in squamous cell carcinomas of the head and neck (17), esophageal cancer (18) and uterine cervical cancer (19). However, no such correlation was found between the Ki-67 labeling index and locoregional control of hypopharyngeal cancer treated with chemoradiotherapy in our results.…”

Section: Discussioncontrasting

confidence: 54%

Analysis and results of Ku and XRCC4 expression in hypopharyngeal cancer tissues treated with chemoradiotherapy

et al. 2012

View full text Add to dashboard Cite

Abstract. DNA double-strand break (DSB) is one of the most serious forms of damage induced by ionizing irradiation. Non-homologous end-joining (NHEJ) is a key mechanism of DNA DSB repair. The immunohistochemical analysis of proteins involved in NHEJ may have potential as a predictive assay for tumor radiosensitivity. We examined the correlation between the expression of proteins involved in DNA DSB in biopsy specimens and the results of chemoradiotherapy in hypopharyngeal cancers. Fifty-seven patients with previously untreated squamous cell carcinoma of the hypopharynx were treated between March 2002 and December 2009. Most patients (75%) had stage III or IV disease. The chemotherapy consisted of cisplatin plus 5FU or S-1. A tumor dose of 50 Gy was usually administered to the primary tumor and regional lymph nodes. Doses of 10-20 Gy were usually added to the primary tumor with reduced fields after 50 Gy. The 5-year disease-free survival rate was 100% for patients in stage I, 90% in stage II, 64% in stage III and 50% in stage IV. In stages I-III, patients with a lower expression of Ku70 or XRCC4 tended to have better locoregional control. These results indicated that a lower expression of Ku70 or XRCC4 may be correlated with higher radiosensitivity. Two patients had distant metastasis alone, of which one had 0% expression of Ku70 and the other had 0% expression of Ku86. The absence of Ku70 or Ku86 expression indicates low DNA-PK activity. Low DNA-PK activity due to a low expression of Ku may result in the genetic alteration of cancer cells, leading to a higher tendency of distant metastasis. This finding suggests that proteins involved in NHEJ may have an impact on the treatment results of chemoradiotherapy in hypopharyngeal cancer.

show abstract

“…As reported previously, cyclin D1 expression is a common genetic alteration as well as a key driver of ESCC 25 . Furthermore, K14, EGFR, cyclin D1, PCNA, and Ki‐67 are upregulated both at RNA and protein levels, while HER2 is elevated only at the protein level in ESCC tissues 26–31 . In agreement with these previous findings, our RNA‐seq data demonstrated that KRT14 , EGFR , CCND1 , PCNA , and MKI67 , but not ERBB2 , were transcriptionally upregulated in ESCC tissues (Figure S4A).…”

Section: Resultssupporting

confidence: 92%

A multi‐omics study delineates new molecular features and therapeutic targets for esophageal squamous cell carcinoma

Jin

Liu

et al. 2021

Clinical & Translational Med

View full text Add to dashboard Cite

Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with inferior prognosis. Here, we conducted comprehensive transcriptomic, proteomic, phosphoproteomic, and metabolomic characterization of human, treatment‐naive ESCC and paired normal adjacent tissues (cohort 1, n = 24) in an effort to identify new molecular vulnerabilities for ESCC and potential therapeutic targets. Integrative analysis revealed a small group of genes that were related to the active posttranscriptional and posttranslational regulation of ESCC. By using proteomic, phosphoproteomic, and metabolomic data, networks of ESCC‐related signaling and metabolic pathways that were closely linked to cancer etiology were unraveled. Notably, integrative analysis of proteomic and phosphoproteomic data pinpointed that certain pathways involved in RNA transcription, processing, and metabolism were stimulated in ESCC. Importantly, proteins with close linkage to ESCC prognosis were identified. By enrolling an ESCC patient cohort 2 (n = 41), three top‐ranked prognostic proteins X‐prolyl aminopeptidase 3 (XPNPEP3), bromodomain PHD finger transcription factor (BPTF), and fibrillarin (FBL) were verified to have increased expression in ESCC. Among these prognostic proteins, only FBL, a well‐known nucleolar methyltransferase, was essential for ESCC cell growth in vitro and in vivo. Furthermore, a validation study using an ESCC patient cohort 3 (n = 100) demonstrated that high FBL expression predicted unfavorable patient survival. Finally, common cancer/testis antigens and established cancer drivers and kinases, all of which could direct therapeutic decisions, were characterized. Collectively, our multi‐omics analyses delineated new molecular features associated with ESCC pathobiology involving epigenetic, posttranscriptional, posttranslational, and metabolic characteristics, and unveiled new molecular vulnerabilities with therapeutic potential for ESCC.

show abstract

Prognostic values of proliferating cell nuclear antigen (PCNA) and Ki-67 for radiotherapy of oesophageal squamous cell carcinomas

Cited by 16 publications

References 35 publications

Expression of the prolyl isomerase Pin1 is a useful indicator of sensitivity to chemoradiotherapy in advanced esophageal squamous cell carcinoma

Expression of the prolyl isomerase Pin1 is a useful indicator of sensitivity to chemoradiotherapy in advanced esophageal squamous cell carcinoma

Analysis and results of Ku and XRCC4 expression in hypopharyngeal cancer tissues treated with chemoradiotherapy

A multi‐omics study delineates new molecular features and therapeutic targets for esophageal squamous cell carcinoma

Contact Info

Product

Resources

About