Low expression of olfactomedin 4 correlates with poor prognosis in smoking patients with non–small cell lung cancer

Su, Wenmei; Luo, Liang; Wu, Fenping; Lai, Zhennan; Li, Xiaofang; Xie, Zhen; Zhi, Tian; Yang, Zhijian; Liang, Rong

doi:10.1016/j.humpath.2015.01.013

Cited by 12 publications

(9 citation statements)

References 24 publications

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“…20 The OLFM4 gene has been analyzed as a putative biomarker in many cancers, including gastrointestinal cancer, head and neck squamous cell carcinoma, cervical neoplasia, nonsmall cell lung cancer, triple-negative breast cancer and distant metastases in estrogen receptor-positive breast carcinoma. [20][21][22][23][24][25][26][27][28][29][30][31][32] In our study, we provide clinical evidence that reduced OLFM4 expression was associated with prostate cancer progression and with DNA methylation of CpG sites in the OLFM4 gene promoter region in human prostate adenocarcinoma. We also found that OLFM4 may play a role in regulating EMT, as well as tumor initiation and growth, in prostate cells.…”

mentioning

confidence: 53%

“…In addition, DNA methylation of the OLFM4 gene has been found to be associated with tumor aggressiveness and patient outcomes in gastric carcinoma . The OLFM4 gene has been analyzed as a putative biomarker in many cancers, including gastrointestinal cancer, head and neck squamous cell carcinoma, cervical neoplasia, nonsmall cell lung cancer, triple‐negative breast cancer and distant metastases in estrogen receptor‐positive breast carcinoma …”

Section: Introductionmentioning

confidence: 99%

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Olfactomedin 4 downregulation is associated with tumor initiation, growth and progression in human prostate cancer

Kim

Liu

et al. 2019

Intl Journal of Cancer

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The olfactomedin 4 (OLFM4) gene has been analyzed as a tumor‐suppressor gene and a putative biomarker in many cancers. In our study, we analyzed the relationship of OLFM4 expression with clinicopathological features and with CpG site methylation in the OLFM4 gene promoter region in human primary prostate adenocarcinoma. OLFM4 protein expression was significantly reduced in prostate cancer tissue compared to adjacent normal tissue and was further significantly reduced in more advanced cancers. Bioinformatic studies with clinical datasets revealed that primary prostate adenocarcinoma patients with reduced OLFM4 mRNA expression exhibited higher Gleason scores and higher preoperative serum prostate‐specific antigen levels, as well as lower recurrence‐free survival. Three of the eight CpG sites in the OLFM4 gene promoter region were hypermethylated in cancerous prostate cells compared to adjacent normal cells, and reduced methylation of eight CpG sites was associated with increased OLFM4 mRNA expression in RWPE1 and PC‐3 cells. Furthermore, knockdown of OLFM4 gene expression was associated with enhanced epithelial–mesenchymal transition (EMT)‐marker expression in RWPE immortalized normal prostate cells. In contrast, restoration of OLFM4 expression in PC‐3 and DU145 prostate cancer cells lacking OLFM4 significantly inhibited both EMT‐marker expression and tumor cell growth in in vitro and in vivo models, indicating that OLFM4 may play a tumor‐suppressor role in inhibiting the EMT program, as well as tumor initiation and growth, in prostate cells. Taken together, these findings suggest that OLFM4 plays an important tumor‐suppressor role in prostate cancer progression and might be useful as a novel candidate biomarker for prostate cancer.

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mentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Olfactomedin 4 downregulation is associated with tumor initiation, growth and progression in human prostate cancer

Kim

Liu

et al. 2019

Intl Journal of Cancer

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“…OLFM4 expression has been reported in several solid cancers and has been shown to be involved in prognosis [35][36][37][38][39][40][41][42][43][44][45]. However, high OLFM4 expression has been shown to be related to both poor and good prognoses in different studies, and no consensus has been reached.…”

Section: Clinicopathological Factorsmentioning

confidence: 99%

High expression of olfactomedin-4 is correlated with chemoresistance and poor prognosis in pancreatic cancer

et al. 2020

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Pancreatic cancer has an extremely poor prognosis, and identification of novel predictors of therapeutic efficacy and prognosis is urgently needed. Chemoresistance-related molecules are correlated with poor prognosis and may be effective targets for cancer treatment. Here, we aimed to identify novel molecules correlated with chemoresistance and poor prognosis in pancreatic cancer. We established 10 patient-derived xenograft (PDX) lines from patients with pancreatic cancer and performed next-generation sequencing (NGS) of tumor tissues from PDXs after treatment with standard drugs. We established a gene-transferred tumor cell line to express chemoresistance-related molecules and analyzed the chemoresistance of the established cell line against standard drugs. Finally, we performed immunohistochemical (IHC) analysis of chemoresistance-related molecules using 80 pancreatic cancer tissues. From NGS analysis, we identified olfactomedin-4 (OLFM4) as having high expression in the PDX group treated with anticancer drugs. In IHC analysis, OLFM4 expression was also high in PDXs administered anticancer drugs compared with that in untreated PDXs. Chemoresistance was observed by in vitro analysis of tumor cell lines with forced expression of OLFM4. In an assessment of tissue specimens from 80 patients with pancreatic cancer, Kaplan-Meier analysis showed that patients in the low OLFM4 expression group had a better survival rate than patients in the high OLFM4 expression group. Additionally, multivariate analysis showed that high expression of OLFM4 was an independent prognostic factor

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“…Our results were consistent with the findings of Guo et al (41), in that promoter methylation regulates the expression of OLFM4. OLFM4 may exert a cancer-promoting effect via apoptosis inhibition during the early stages, suggesting that OLFM4 inactivation may be crucial for tumor progression or metastasis (42). By contrast, OLFM4 was found to be highly expressed in normal prostate tissue, moderately expressed in benign prostatic hyperplasia tissues, and not expressed in prostate cancer tissues, indicating that OLFM4 acted as a tumor-suppressing gene (7).…”

Section: Genementioning

confidence: 99%

Altered DNA methylation is associated with aberrant stemness gene expression in early‑stage HNSCC

Suzuki

Yamazaki

Honda³

et al. 2019

Int J Oncol

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Low expression of olfactomedin 4 correlates with poor prognosis in smoking patients with non–small cell lung cancer

Cited by 12 publications

References 24 publications

Olfactomedin 4 downregulation is associated with tumor initiation, growth and progression in human prostate cancer

Olfactomedin 4 downregulation is associated with tumor initiation, growth and progression in human prostate cancer

High expression of olfactomedin-4 is correlated with chemoresistance and poor prognosis in pancreatic cancer

Altered DNA methylation is associated with aberrant stemness gene expression in early‑stage HNSCC

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