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. 2023 Oct;52(9):849-859.
doi: 10.1111/jop.13467. Epub 2023 Aug 13.

Elevated translationally controlled tumour protein promotes oral cancer progression and poor outcome

Dipti Sharma  1   2 , Sagar N Pawar  1 , Prasad Sulkshane  1 , Rohit Waghole  1 , Mohd Yasser  1 , Sushil S Pawar  3 , Sadhana Kannan  4 , Nazia Chaudhary  2   5 , Anjali Kalwar  1 , Rahul Patil  3 , Sudhir Nair  6 , Sorab N Dalal  2   5 , Tanuja Teni  1   2
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Elevated translationally controlled tumour protein promotes oral cancer progression and poor outcome

Dipti Sharma et al. J Oral Pathol Med. 2023 Oct.

Abstract

Background: Translationally controlled tumour protein (TCTP) is a multifunctional protein elevated in multiple cancers. However, studies on its role in oral carcinogenesis and prognosis are rare. We recently reported the role of its interacting partner, MCL1, in oral cancer progression and outcome. Hence, the present study aimed to assess TCTP expression in oral tumorigenesis and its association with patient outcomes alone and in combination with MCL1.

Methods: TCTP expression was assessed by immunohistochemistry and immunoblotting in oral tissues and cells, respectively. Cell viability post siRNA/dihydroartemisinin treatment was analysed by tetrazolium salt assay. Cell survival, invasion and tumorigenic potential post TCTP knockdown were assessed by clonogenic, Matrigel and soft-agar assays, respectively. The association of TCTP with patient outcome was analysed by Kaplan-Meier and Cox regression.

Results: TCTP was significantly overexpressed in oral premalignant lesions (p < 0.0001), oral tumours (p < 0.0001) and oral dysplastic and cancer cells versus normal oral mucosa and also in recurrent (p < 0.05) versus non-recurrent oral tumours. Further, elevated TCTP was significantly (p < 0.05) associated with poor recurrence free survival (RFS) and poor overall survival (OS; hazard ratio = 2.29; p < 0.05). Intriguingly, the high co-expression of TCTP and MCL1 further reduced the RFS (p < 0.05) and OS (p < 0.05; hazard-ratio = 3.49; p < 0.05). Additionally, TCTP knockdown decreased survival (p < 0.05), invasion (p < 0.01) and in vitro tumorigenic potential (p < 0.0001). Dihydroartemisinin treatment reduced TCTP levels and viability of oral cancer cells.

Conclusion: Our studies demonstrate an oncogenic role of TCTP in oral cancer progression and poor outcome. Thus, TCTP may be a potential prognostic marker and therapeutic target in oral cancers.

Keywords: TCTP; invasion; oral squamous cell carcinoma; prognosis; recurrence.

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