Abstract
Simple SummaryOral cancer is one of the most frequent malignancies in the world, with a poor prognosis. The absence of accurate biomarkers for predicting oral cancer progression is the primary cause of treatment failures. Multiple studies have shown that cancer stem cells play a critical role in tumor growth and chemo resistance. We uncovered, for the first time, the importance of combinatorial expression of stem cell related molecules CXCR-4 and CD-133 as possible biomarkers to predict poor prognosis of oral squamous cell carcinoma. The findings will aid in the identification of high-risk cases in order to provide appropriate therapy.The activation of the SDF-1/CXCR-4 pathway is crucial for the invasion and metastasis of oral cancer cells. The CXCR-4 positive cells possess stem cell characteristics and express the cancer stem cell marker, CD133, in tumors of colon and pancreas. Despite several studies, the co-expression of CXCR-4 and CD133 and its significance is still largely unknown in oral cancer. Therefore, we aimed to investigate the impact of CXCR-4 and CD133 double positivity in the prognosis of oral cancer. The significance of PKC-δ, one of the key signaling molecules that regulates CXCR-4, was also analyzed. Immunohistochemistry and double immunofluorescence was used to investigate the co-localization of CXCR-4, PKC-δ and CD133 in the human tissues and cell lines of oral squamous cell carcinoma. The expression of CXCR-4, PKC-δ and CD133 were found to be higher in poorly differentiated and lymph node metastasis-positive cases. Interestingly, CXCR-4 positive cells showed positive staining for PKC-δ and CD133 in oral cancer tissue and cell lines. Moreover, CXCR-4+/CD133+ and CXCR-4+/PKC-δ+ double positive cases have the worst survival. We discovered, for the first time, that patients with expression of both CXCR-4 and CD133 have a lower survival rate, and CXCR-4+/CD133+, as well as CXCR-4+/PKC-δ+ double positivity, can be utilized to predict poor prognosis. CXCR-4, PKC-δ and CD133 might regulate aggressiveness and invasion of oral cancer cells.
Highlights
Cancer is a complex heterogeneous disease that develops as a consequence of genetic and epigenetic alterations
Cancers 2021, 13, 5895 of CXCR-4, PKC-δ and CD133 in oral cancer tissues and cell line. We studied their correlation with clinicopathological factors and the possibility of using CXCR-4/CD133 as well as CXCR-4/PKC-δ double positivity to predict poor prognosis in oral cancer
Increased expression of CXCR-4, PKC-δ and CD133 indicates their role in the progression of oral cancer
Summary
Cancer is a complex heterogeneous disease that develops as a consequence of genetic and epigenetic alterations. Oncogene and tumor suppressor gene alterations were highly crucial for the development of cancer [1]. Several reports have pointed out the significance of using a combination of functionally related markers to predict poor prognosis of oral cancer. The re-expression of stemness markers such as Oct-4, c-Myc, Nanog and CD44 in oral cancer tissues and their association with recurrence provides a platform for Scientists to explore their significance in predicting poor prognosis [3,4]. We have investigated the expression pattern of CXCR4, PKC-δ and CD133 in oral squamous cell carcinoma. The CXCR-4+/CD133+ and CXCR-4+/PKC-δ+ double positivity was analyzed to predict poor prognosis
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
