Chromobox 2 Expression Predicts Prognosis After Curative Resection of Oesophageal Squamous Cell Carcinoma

Abstract

Background/Aim: To investigate the function of chromobox 2 (CBX2) in oesophageal squamous cell carcinoma (OSCC). Materials and Methods: We used real-time quantitative reverse transcription PCR (qRT-PCR) and immunohistochemistry to determine CBX2 expression levels in 13 human OSCC cell lines and clinical specimens of two independent cohorts of patients with OSCC. Results: PCR array analysis revealed that CBX2 was co-ordinately expressed with WNT5B in OSCC cell lines. RT-qPCR analysis of clinical samples revealed a high tumour-specific CBX2 expression compared with normal oesophageal tissues. High CBX2 expression was significantly associated with shorter disease-specific survival, hematogenous recurrence, and overall recurrence. Analysis of tissue microarrays of one cohort revealed that patients with higher CBX2 levels tended to have a shorter disease-specific survival. Conclusion: CBX2 overexpression in OSCC tissues may serve as a novel biomarker for predicting survival and hematogenous recurrence. The main histopathological subtypes of oesophageal carcinoma, the sixth leading cause of cancer-related mortality worldwide (1), are adenocarcinoma and oesophageal squamous cell carcinoma (OSCC). The latter is the predominant subtype in Asia and Africa (2). OSCC is generally associated with poor prognosis, mainly because of its high potential to metastasize, which accounts for its dismal overall survival rate of <40%, despite radical treatment (3). A primary goal of efforts to improve the management of OSCC and patients' outcomes is to develop methods that accurately predict the risk of recurrence and survival after curative oesophageal resection (4, 5). Specific biomarkers that predict the recurrence pattern of OSCC, particularly for hematogenous recurrence after radical treatment, will likely contribute to improving patients' outcomes and are therefore the focus of our research. We the aim to identify novel biomarkers, we first focused on the chromobox 2 (CBX2) gene, a member of the chromobox (CBX) gene family, because of its reported association with certain cancers (6-8). CBX2 encodes a subunit of the polycomb group (PcG), whose members form complexes that mediate homeostasis (9). These proteins regulate the expression of numerous genes that control the maintenance, differentiation and proliferation of adult stem cells and cancer cells (10). Biochemical characterization led to the categorization of PcG complexes into two subtypes: Polycomb repressive complex (PRC) 1 and PRC2 (6, 11, 12). The CBX gene family comprises CBX2, CBX4, CBX6, CBX7 and CBX8, which encode components of PRC1 (11). PRC1 members are associated with tumourigenesis. For example, CBX4 plays important roles in cellular proliferation and in the repair of DNA damage in certain human tumours (13, 14). CBX6 was identified as a susceptibility loci by a genome-wide association study on bladder cancer (15). Numerous studies have shown that CBX7 is specifically 391 This article is freely accessible online.

Knockdown of lncRNA DLEU1 inhibits the tumorigenesis of oral squamous cell carcinoma via regulation of miR‑149‑5p/CDK6 axis

“…Oral squamous cell carcinoma (OSCC) is one of the most frequent malignant tumors with a poor prognosis ( 1 , 2 ), and the incidence of OSCC is ~300,000 new cases per year worldwide ( 3 ). Recent reports revealed that betel quid chewing, smoking and human papillomavirus infections are the three biggest risk factors that contribute to the tumorigenesis of OSCC ( 4 , 5 ).…”

Increased STX3 transcript and protein levels were associated with poor prognosis in two independent cohorts of esophageal squamous cell carcinoma patients

“…A total of 21 ESCC cell lines, specifically KYSE30, KYSE70, KYSE140, KYSE150, KYSE180, KYSE270, KYSE410, KYSE450, KYSE510, KYSE590, KYSE890, KYSE1170, KYSE1260, KYSE1440, NUEC2, TE1, TE2, TE3, WSSC, TT, and TTn, along with Het‐1A, a non‐cancerous epithelial cell line, were purchased from the Japanese Collection of Research Bioresources Cell Bank (Osaka, Japan), the American Type Culture Collection (Manassas, VA, USA), or were established at Nagoya University 5 . The cells were cultured in a humidified incubator at 37°C with an atmosphere composition of 5% CO 2 using RPMI‐1640 (Sigma‐Aldrich, St. Louis, MO, USA) supplemented with 10% fetal bovine serum and antibiotics 24 …”

Chromobox proteins in cancer: Multifaceted functions and strategies for modulation (Review)

“…Expression of CBXs in cancers. Compared with normal tissues or paracancerous tissues, the expression of all or some of the CBX1/2/3/4/5/8 members is upregulated in most cancer tissues, including glioma (67-69), tongue squamous cell carcinoma (TSCC) (70), head and neck squamous cell carcinoma (HNSCC) (71), breast cancer (BC) (15,(72)(73)(74)(75)(76)(77)(78)(79)(80), non-small cell lung cancer (NSCLC) (81)(82)(83)(84)(85), esophageal cancer (EC) (86)(87)(88)(89)(90), gastric cancer (GC) (91)(92)(93)(94)(95)(96)(97)(98), pancreatic adenocarcinoma (PAAD) (99,100), colorectal cancer (CRC) (101-104), urinary bladder cancer (UBC) (105), sarcoma (106) and osteosarcoma (107,108). As a tumor suppressor, CBX7 is expressed at low levels in most tumors, such as glioma, HNSCC (71), EC (87,88), GC (93)(94)(95)(96)(97)(98), PAAD (109), CRC (103,104), clear cell r...…”

“…invasion↑ osteosarcoma ( 107) was reported to be associated with more robust metastatic characteristics, indicating that CBX3 has an important role in tumor metastasis. High expression of CBX2/3/8 in glioma (67,69), CBX2 in EC (89) and CBX1 in HCC (115) was indicated to lead to a high probability of tumor recurrence. In terms of other cancer characteristics, CBX2/6/7 is closely related to the isocitrate dehydrogenase mutation in glioma (68), CBX2 is related to a human epidermal growth factor receptor (EGFR)2-positive status of BC ( 74) and CBX3 is related to EGFR mutation in NSCLC (82).…”