Multi-cohort validation: A comprehensive exploration of prognostic marker in clear cell renal cell carcinoma

Kidney cancer is among the top ten prevalent cancers and has seen a global rise in incidence, accounting for 400,000 new cancer cases and 175,000 annual deaths [1], [2]. Renal cell carcinoma (RCC) accounts for approximately 85 % of kidney cancers [3]. Clear cell RCC (ccRCC), the predominant subtype of RCC, constitutes nearly 70 % [4], [5]. According to prior researches, the initial diagnosis reveals that around 70 % of RCC cases present as either local or advanced stages [6]. Despite the effective surgical treatment available for early-stage ccRCC, it is important to note that a substantial portion of cases (approximately 30–50 %) ultimately progress to metachronous distant metastasis, resulting in detrimental outcomes [7]. Moreover, it is well-established that ccRCC exhibits a high resistance to radio- and cytotoxic chemotherapy [8], [9]. Thus, the metastatic nature and treatment limitations of ccRCC lead to a poor prognosis [10], [11], [12]. Consequently, there is a crucial need for new biomarkers for cancer prognosis and treatment.

TYMP, which encodes adenosine phosphorylase, is a cytosolic metabolic enzyme [13], [14]. Notably, TYMP has been shown to play a crucial role in cell proliferation and angiogenesis. It is also considered as a rate-limiting enzyme in chemotherapy drug metabolism [15], [16]. Increasing studies have associated TYMP with tumor development owing to its capability to inhibit neoplastic cell apoptosis [17]. Yanagihara et al. reported that TYMP is highly expressed in liver, lung and breast tumors [18]. Additionally, TYMP has been demonstrated to exert favourable prognostic value in gastric and colorectal cancers [19], [20]. However, the value of TYMP in ccRCC remains unclear.

Herein, the potential of TYMP in ccRCC was investigated in multiple aspects (transcription level, clinical implications, immune infiltration, immune checkpoints, drug susceptibility, and biological function). The elevated expression of TYMP in ccRCC was found via mining the data of public databases. Integrating clinicopathologic data revealed that high TYMP expression was correlated with worse clinicopathologic grading and prognosis. The knockdown of TYMP impedes proliferation, invasion and migration of RCC cells. Collectively, this study highlights that TYMP may serve as a viable prognostic target for ccRCC.

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