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- Israelsson, Pernilla, et al.
(författare)
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Immunoreactivity of LMO7 and other molecular markers as potential prognostic factors in oropharyngeal squamous cell carcinoma
- 2024
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Ingår i: BMC Oral Health. - : BioMed Central (BMC). - 1472-6831. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite the better prognosis associated with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), some patients experience relapse and succumb to the disease; thus, there is a need for biomarkers identifying these patients for intensified treatment. Leucine-rich repeats and immunoglobulin-like domain (LRIG) protein 1 is a negative regulator of receptor tyrosine kinase signaling and a positive prognostic factor in OPSCC. Studies indicate that LRIG1 interacts with the LIM domain 7 protein (LMO7), a stabilizer of adherence junctions. Its role in OPSCC has not been studied before.Methods: A total of 145 patients diagnosed with OPSCC were enrolled. Immunohistochemical LMO7 expression and staining intensity were evaluated in the tumors and correlated with known clinical and pathological prognostic factors, such as HPV status and LRIG1, CD44, Ki67, and p53 expression.Results: Our results show that high LMO7 expression is associated with significantly longer overall survival (OS) (p = 0.044). LMO7 was a positive prognostic factor for OS in univariate analysis (HR 0.515, 95% CI: 0.267–0.994, p = 0.048) but not in multivariate analysis. The LMO7 expression correlated with LRIG1 expression (p = 0.048), consistent with previous findings. Interestingly, strong LRIG1 staining intensity was an independent negative prognostic factor in the HPV-driven group of tumors (HR 2.847, 95% Cl: 1.036–7.825, p = 0.043).Conclusions: We show for the first time that high LMO7 expression is a positive prognostic factor in OPSCC, and we propose that LMO7 should be further explored as a biomarker. In contrast to previous reports, LRIG1 expression was shown to be an independent negative prognostic factor in HPV-driven OPSCC.
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| 2. |
- Oda, Husam, 1975-
(författare)
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Leucine-rich repeats and immunoglobulin-like domain (LRIG) proteins : possible prognostic markers in vulvar squamous cell carcinoma, endometrial carcinoma, and oropharymgeal squamous cell carcinoma
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The human leucine-rich repeats and immunoglobulin-like domain (LRIG) gene family comprises three genes, LRIG1, LRIG2 and LRIG3, which encode the LRIG1, LRIG2 and LRIG3 proteins, respectively. Previous stidies have revealed the different prognostic roles of these proteins in different cancers, and it has been shown that LRIG1 functions as a tumour suppressor in certain cancers via its negative regulation of several receptor tyrosine kinases. Much less is known about the functionof LRIG2 and LRIG3. The expression of all three LRIG genes has been studied with human papillomavirus (HPV). In particular, expression of LRIG1 has been associated with improved survival in cervical, vaginal, and oropharyngeal cancers. Since LRIG1 has been shown to predict sensitivity to paltinum-based chemotherapy when studied in different cell lines, the possible role of LRIG protein expression in HPV-associated and other cancers may be interesting to investigate furthur.The overall aim of this thesis was to evaluate the immunoreactivity of LRIGs in vulvar squamous cell carcinoma (VSCC), endometrial carcinoma (EC) and oropharyngeal squamous cell carcinoma (OPSCC) and to investigate the potential prognostic value of LRIG proteins in association with HPV and p16 status in VSCC and OPSCC and to investigate the possible prognostic value of LMO7 and other prognostic markers of interest. Expression of the LRIG proteins and other markers was evaluated with immunohistochemistry, and HPV status was determined by PCR.In VSCC, high immunoreactivity of LRIG2 and LMO7 was associated with good survival. LRIG1 was not a significant prognostic factor in VSCC. We also conducted a pilot study to evaluate the immunoreactivity of LRIG proteins in 75 women with EC. Most of the patients in this cohort had very high positivity for LRIG proteins. High expression of LRIG3 was associated with better survival. LRIG1 and LRIG2 expression in tumours had no impact on prognosis in this study, but this should be interpreted with great caution due to the limited size of the cohort. Finally, high expression of LMO7 was associated with improved survival in OPSCC. In this cohort of 143 patients, LRIG1 expression was associated with worse survival in HPV-driven tumours. This is in contrast to previous published work where high LRIG1 expression has been associated with good survival. Notably, in both the VSCC and OPSCC cohort, a new polyclonal LRIG1 antibody was used in contrast to that in a previous study of OPSCC.In conclusion, we report additional data on the prognosticvalue of LRIG proteins in smaller cohort of VSCC, EC and OPSCC and suggest that these molecular markers need to be investigated furthur to elucidate possible clinical implications. In addition, a new monoclonal antibody against LRIG1 needs to be developed to ensure the reproducibility of the data.
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