scholarly journals Identification of SPRR3 as a novel diagnostic/prognostic biomarker for oral squamous cell carcinoma via RNA sequencing and bioinformatic analyses

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9393
Author(s):  
Lu Yu ◽  
Zongcheng Yang ◽  
Yingjiao Liu ◽  
Fen Liu ◽  
Wenjing Shang ◽  
...  

Oral squamous cell carcinoma (OSCC) has always been one of the most aggressive and invasive cancers among oral and maxillofacial malignancies. As the morbidity and mortality of the disease have increased year by year, the search for a promising diagnostic and prognostic biomarker for the disease is becoming increasingly urgent. Tumorous and adjacent tissues were collected from three OSCC sufferers and we obtained 229 differentially expressed genes (DEGs) between tumor and normal tissues via high-throughput RNA sequence. Function and pathway enrichment analyses for DEGs were conducted to find a correlation between tumorigenesis status and DEGs. Protein interaction network and molecular complex detection (MCODE) were constructed to detect core modules. Two modules were enriched in MCODE. The diagnostic and prognostic values of the candidate genes were analyzed, which provided evidence for the candidate genes as new tumor markers. Small Proline Rich Protein 3 (SPRR3), a potential tumor marker that may be useful for the diagnosis of OSCC, was screened out. The survival analysis showed that SPRR3 under expression predicted the poor prognosis of OSCC patients. Further experiments have also shown that the expression of SPRR3 decreased as the malignancy of OSCC increased. Therefore, we believe that SPRR3 could be used as a novel diagnostic and prognostic tumor marker.

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1842
Author(s):  
Yawei Sun ◽  
Shuai Wang ◽  
Xingwei Zhang ◽  
Zhuhao Wu ◽  
Zihui Li ◽  
...  

Background: Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a key enzyme that catalyzes the hydroxylation of lysine, plays a crucial role in the progression of several solid tumors. However, its spatial expression profile and prognostic significance in oral squamous cell carcinoma (OSCC) have not been revealed. Materials: Mass spectrometry was used to explore amino acid perturbations between OSCC tumor tissues and paired normal tissues of 28 patients. Then, PLOD2 mRNA and protein levels were assessed using several public databases and 18 pairs of OSCC patients’ tissues. Additionally, PLOD2 spatial expression profiles were investigated in 100 OSCC patients by immunohistochemistry and its diagnostic and prognostic values were also evaluated. Lastly, gene set enrichment analysis (GSEA) was used to investigate the potential functions of PLOD2 in OSCC. Results: Lysine was significantly elevated in OSCC tissues and could effectively distinguish tumor from normal tissues (AUC = 0.859, p = 0.0035). PLOD2 mRNA and protein levels were highly increased in tumor tissues of head and neck squamous cell carcinoma (HNSCC) (p < 0.001) and OSCC compared with those in nontumor tissues (p < 0.001). Histopathologically, PLOD2 was ubiquitously expressed in tumor cells (TCs) and fibroblast-like cells (FLCs) of OSCC patients but absent in tumor-infiltrating lymphocytes (TILs). Patients with highly expressed PLOD2 in TCs (PLOD2TCs) and FLCs (PLOD2FLCs) showed poor differentiation, a worse pattern of invasion (WPOI) and more lymph node metastasis (LNM), contributing to higher postoperative metastasis risk and poor survival time. However, PLOD2FLCs rather than PLOD2TCs was an independent risk factor for survival outcomes in OSCC patients. Molecularly, GSEA demonstrated highly expressed PLOD2 was mainly enriched in epithelial–mesenchymal transformation (EMT), TGF-beta signaling and hypoxia pathway, which are associated with poor clinical outcomes of OSCC patients. Conclusions: PLOD2 was a poor prognostic biomarker for OSCC patients and may affect the metastasis of OSCC through EMT pathway. These findings might shed novel sights for future research in PLOD2 targeted OSCC therapy.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samapika Routray ◽  
Ravindra Kumar ◽  
Keshava K. Datta ◽  
Vinuth N. Puttamallesh ◽  
Aditi Chatterjee ◽  
...  

AbstractOral squamous cell carcinoma (OSCC) is known for its aggressiveness associated with poor prognosis. The molecular mechanisms underlying the invasion and metastasis are still poorly understood. An improved understanding of these mechanisms shall precede the development of new diagnostic tools and targeted therapies. We report an integrated approach using bioinformatics to predict candidate genes, coupled with proteomics and immunohistochemistry for validating their presence and involvement in OSCC pathways heralding invasion and metastasis. Four genes POSTN, TNC, CAV1 and FSCN1 were identified. A protein–protein interaction network analysis teamed with pathway analysis led us to propose the role of the identified genes in invasion and metastasis in OSCC. Further analyses of archived FFPE blocks of various grades of oral cancer was carried out using TMT-based mass spectrometry and immunohistochemistry. Results of this study expressed a strong communiqué and interrelationship between these candidate genes. This study emphasizes the significance of a molecular biomarker panel as a diagnostic tool and its correlation with the invasion and metastatic pathway of OSCC. An insight into the probable association of CAF's and these biomarkers in the evolution and malignant transformation of OSCC further magnifies the molecular-biological spectrum of OSCC tumour microenvironment.


Author(s):  
Yongzhi XU ◽  
Fang FANG ◽  
Jinghui WANG ◽  
Chunli ZHAO ◽  
Jingyang ZHAO ◽  
...  

Background: Expression of miR‑92b in oral squamous cell carcinoma (OSCC) rat tissue and its effect on the OSCC CAL‑27 cells were investigated. Methods: The study was performed in Qingdao Stomatological Hospital, Qingdao, China on December 2018. Thirty Wistar rats were used to construct models of oral squamous cell carcinoma. CAL‑27 cells trascfected by Lipofectamine 2000 were divided into miR‑92b inhibitor, miR‑NC and blank groups. RT‑qPCR was used for the detection of the expression level of miR‑92b, and MTT and flow cytometry were carried out for the detection of the effect of miR‑92b on the proliferation and apoptosis of CAL‑27 cells, respectively. Results: The expression level of miR‑92b was significantly higher in tumor tissues than that in normal tissues (P<0.001). The miR‑92b inhibitor group had significantly lower proliferation ability but higher apoptosis rate of CAL‑27 cells than the miR‑NC and blank groups. After miR‑92b was downregulated by trans-fecting cells, the expression level of miR‑92b was significantly lower in the miR‑92b inhibitor group than that in the miR‑NC and blank groups. Conclusion: miR‑92b inhibitor can inhibit the proliferation of CAL‑27 cells and promote apoptosis, which provides certain references for clinical treatment. It is expected to be a potential target for treating OSCC.


2008 ◽  
Vol 99 (4) ◽  
pp. 655-662 ◽  
Author(s):  
K Ota ◽  
H Fujimori ◽  
M Ueda ◽  
S Shiniriki ◽  
M Kudo ◽  
...  

2021 ◽  
Author(s):  
Jingjing Dong ◽  
Jingquan He ◽  
Zeyu Zhang ◽  
Wei Zhang ◽  
Yixi Li ◽  
...  

Abstract Background Lysine acetylation (Kac) favors gene transcription and activates various genes involved in the regulation of oncogenesis, whereas the acetylation profiling of oral squamous cell carcinoma (OSCC) is unknown. We performed lysine acetylation analyses to achieve a comprehensive profile and revealed the specific pathogenesis in patients with OSCC. Methods Liquid chromatography − tandem mass spectrometry (LC-MS/MS) was utilized to investigate lysine acetylation features of tumor tissues and adjacent normal tissues from 9 patients with OCSS. Results Among the upregulated different acetylation proteins (DAPs), the biological process of GO analysis was closely related to cellular response to regulation of apoptotic process, and regulation of programmed cell death. KEGG enrichment analysis was associated with HIF-1 signaling pathway, ferroptosis, and JAK-STAT signaling pathway. In PPI network, seven differently Kac proteins (SRSF1, HNPNPM, PRPF8, DHX9, DHX15, RBMX, SNRPG) in MCODE1 and the top 30 hub gene involved in mRNA splicing process and spliceosome pathway. Six differently Kac modified proteins of RPS15A, RPL11, RPS11, RPS3, RPL24, RPL19 in MCODE1 was enriched in ribosome pathway, particular lower expression of RPS3, RPL24 and RPL19 were related to the overall survival of OSCC. Conclusion This study contributes a foundation for understanding the functions of Kac modification in OSCC and investigates lysine acetylation on proteins involved in ribosome pathway, particularly the ones that acted as hub genes and related to the OSCC survival, which may be a potential therapeutic direction of OSCC in the future.


2019 ◽  
Author(s):  
Jain Anu ◽  
Mallupattu Sumanth Kumar ◽  
Thakur Reetu ◽  
Mohindra Satyawati ◽  
Bal Amanjit ◽  
...  

AbstractPURPOSECR-1 (CR-1) is an oncofetal protein with its role as a key factor in early process of carcinoma has been evaluated in cases of various cancers. However, very few studies have reported its role in oral cancers, which is the sixth most common cancer around the world, particularly with high prevalence in developing countries. Oral squamous cell carcinoma (OSCC) is the most predominant (90%) of all the histological types of oral cancer. Late detection, associated with increased morbidity and mortality, is mainly attributed to non-availability of a suitable biomarker for the disease. In the present pilot study we have evaluated the role of soluble CR-1, in serum as a potential tumor marker for OSCC.METHODSCR-1 was estimated using sandwich ELISA in serum samples of 50 biopsy proven OSCC patients (pre and post treatment) along with age and gender matched healthy controls. Immunohistochemistry was also done in corresponding tumor tissue sections to check the expression of CR-1.RESULTSPre-treatment CR-1 was found to be 2.25 fold higher in serum of OSCC patients as compared to control (p<0.0001***), which was reduced to 1.6 folds post treatment (p=0.0006***). CR-1 levels were comparatively higher in early stage of disease. Upon IHC 80% of the cases were found to be positive for CR-1.CONCLUSIONThis study provides evidence that serum levels of CR-1 are elevated in patients of Oral Squamous Cell Carcinoma, which decrease post treatment. Also, the association of expression of protein with tumor progression predicts CR-1 as a molecule that can be further evaluated as a potential tumor maker in OSCC.


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