Upregulated long non-coding RNA LINC00152 expression is associated with progression and poor prognosis of tongue squamous cell carcinoma

doi:10.7150/jca.17510

. 2017 Feb 11;8(4):523-530.

doi: 10.7150/jca.17510. eCollection 2017.

Upregulated long non-coding RNA LINC00152 expression is associated with progression and poor prognosis of tongue squamous cell carcinoma

Jianjun Yu¹, Yan Liu², Can Guo³, Shanshan Zhang⁴, Zhaojian Gong⁵, Yanyan Tang⁶, Liting Yang⁶, Yi He², Yu Lian⁶, Xiayu Li⁷, Hao Deng⁷, Qianjin Liao⁸, Xiaoling Li⁸, Yong Li⁹, Guiyuan Li⁸, Zhaoyang Zeng³, Wei Xiong⁸, Xinming Yang¹⁰

Affiliations

¹ Department of Head and Neck Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China;; Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China;; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Cancer Research Institute, Central South University, Changsha, Hunan, China.
² Department of Head and Neck Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China;; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Cancer Research Institute, Central South University, Changsha, Hunan, China.
³ The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Cancer Research Institute, Central South University, Changsha, Hunan, China;; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁴ The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁵ Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China;; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Cancer Research Institute, Central South University, Changsha, Hunan, China;; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁶ The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Cancer Research Institute, Central South University, Changsha, Hunan, China.
⁷ Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁸ Department of Head and Neck Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China;; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Cancer Research Institute, Central South University, Changsha, Hunan, China;; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁹ The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Cancer Research Institute, Central South University, Changsha, Hunan, China;; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China;; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
¹⁰ Department of Head and Neck Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China;; Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

PMID: 28367232
PMCID: PMC5370496
DOI: 10.7150/jca.17510

Upregulated long non-coding RNA LINC00152 expression is associated with progression and poor prognosis of tongue squamous cell carcinoma

Jianjun Yu et al. J Cancer. 2017.

. 2017 Feb 11;8(4):523-530.

doi: 10.7150/jca.17510. eCollection 2017.

Authors

Affiliations

¹ Department of Head and Neck Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China;; Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China;; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Cancer Research Institute, Central South University, Changsha, Hunan, China.
² Department of Head and Neck Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China;; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Cancer Research Institute, Central South University, Changsha, Hunan, China.
³ The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Cancer Research Institute, Central South University, Changsha, Hunan, China;; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁴ The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁵ Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China;; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Cancer Research Institute, Central South University, Changsha, Hunan, China;; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁶ The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Cancer Research Institute, Central South University, Changsha, Hunan, China.
⁷ Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁸ Department of Head and Neck Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China;; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Cancer Research Institute, Central South University, Changsha, Hunan, China;; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁹ The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Cancer Research Institute, Central South University, Changsha, Hunan, China;; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China;; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
¹⁰ Department of Head and Neck Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China;; Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

PMID: 28367232
PMCID: PMC5370496
DOI: 10.7150/jca.17510

Abstract

Altered expression of long non-coding RNAs (lncRNAs) associated with human carcinogenesis and might be used as diagnosis and prognosis biomarkers. However, the expression of lncRNAs in tongue squamous cell carcinoma (TSCC) and their relevance on the diagnosis, progression and prognosis of TSCC have not been thoroughly elucidated. To discover novel TSCC-related lncRNAs, we analyzed the lncRNA expression patterns in two sets of previously published TSCC gene expression profile data (GSE30784 and GSE9844), and found that long intergenic non-coding RNA 152 (LINC00152) was significantly upregulated in TSCC samples. We then detected LINC00152 expression in two other cohorts of TSCC samples. Quantitative Real time PCR (qRT-PCR) results indicated that LINC00152 was highly expressed in 15 primary TSCC biopsies when compared with 14 adjacent non-tumor tongue squamous cell epithelium samples. The expression of LINC00152 was also measured in 182 paraffin-embedded human TSCC tissues by in situ hybridization, increased expression of LINC00152 was significantly correlated with TSCC progression, such as T stage (p = 0.009), N stage (p = 0.036), TNM stage (p = 0.017), and associated with relapse (p < 0.001), and invasion (p < 0.001). Kaplan-Meier analysis demonstrated that increased LINC00152 expression contributed to both poor overall survival (p = 0.006) and disease-free survival (p = 0.007) of TSCC patients. These findings suggest that LINC00152 might serve as a potential biomarker for early detection and prognosis prediction of TSCC.

Keywords: Long non-coding RNA (LncRNA); long intergenic non-coding RNA 152 (LINC00152); metastasis; prognosis.; tongue squamous cell carcinoma (TSCC).

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

**Figure 1**
**Dysregulated lncRNA expression analysis using two independent TSCC cohorts and cDNA microarray analysis. A.** Schematic overview of the workflow used to identify dysregulated lncRNAs in two TSCC microarray data cohorts (GSE9844 and GSE30784). B. Heatmap of 12 dysregulated lncRNAs mined from the GEO data sets.

**Figure 2**
**LINC00152 expression was upregulated in three independent cohorts of TSCC biopsies.** T, tumor; N, non-tumor lingual mucous membrane. LINC00152 expression, as measured by Affymetrix microarray, was upregulated TSCC biopsies when compared with non-tumor lingual mucous membrane tissues in GSE30784 (A) and GSE9844 (B). C. LINC00152 mRNA expression was measured in 15 TSCC tissues and 14 adjacent non-tumor tissues using quantitative PCR (qRT-PCR).

**Figure 3**
**The relationship between LINC00152 and pathological clinical feature**. A. LINC00152 expression was measured by *in situ* hybridization in paraffin embedded non-tumor lingual mucous membrane (N, n = 46) and TSCC biopsies (T, n = 182). Representative cases of normal lingual mucous membrane (N) and TSCC biopsies were shown. B. LINC00152 expression in tumor compared to adjacent non-tumor lingual mucous membrane. C. Correlation of LINC00152 expression and tumor size in TSCC patients. D. Correlation of LINC00152 expression and lymph node metastasis in TSCC patients. E. Correlation of LINC00152 expression and TNM stage in TSCC patients. F. Correlation of LINC00152 expression and recurrence of TSCC patients. G. Correlation of LINC00152 expression and tongue muscle invasion in TSCC patients.

**Figure 4**
**Kaplan-Meier survival curves in TSCC patients according to LINC00152 expression levels.** The highly expressed LINC00152 was correlated with shorter overall survival (A) or Relapse free survival (B) of TSCC patients.

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References

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[1] Kimple AJ, Welch CM, Zevallos JP. et al. Oral cavity squamous cell carcinoma-an overview. Oral Health Dent Manag. 2014;13:877–82. - PubMed

[2] Kimple AJ, Welch CM, Zevallos JP. et al. Oral cavity squamous cell carcinoma-an overview. Oral Health Dent Manag. 2014;13:877–82. - PubMed

[3] Schwam ZG, Judson BL. Improved prognosis for patients with oral cavity squamous cell carcinoma: Analysis of the National Cancer Database 1998-2006. Oral Oncol. 2016;52:45–51. - PubMed

[4] Schwam ZG, Judson BL. Improved prognosis for patients with oral cavity squamous cell carcinoma: Analysis of the National Cancer Database 1998-2006. Oral Oncol. 2016;52:45–51. - PubMed

[5] Bagan J, Sarrion G, Jimenez Y. Oral cancer: clinical features. Oral Oncol. 2010;46:414–7. - PubMed

[6] Bagan J, Sarrion G, Jimenez Y. Oral cancer: clinical features. Oral Oncol. 2010;46:414–7. - PubMed

[7] Sciubba JJ. Oral cancer. The importance of early diagnosis and treatment. Am J Clin Dermatol. 2001;2:239–51. - PubMed

[8] Sciubba JJ. Oral cancer. The importance of early diagnosis and treatment. Am J Clin Dermatol. 2001;2:239–51. - PubMed

[9] Stransky N, Egloff AM, Tward AD. et al. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011;333:1157–60. - PMC - PubMed

[10] Stransky N, Egloff AM, Tward AD. et al. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011;333:1157–60. - PMC - PubMed

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Upregulated long non-coding RNA LINC00152 expression is associated with progression and poor prognosis of tongue squamous cell carcinoma

Affiliations

Upregulated long non-coding RNA LINC00152 expression is associated with progression and poor prognosis of tongue squamous cell carcinoma

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Abstract

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