Differential expression of TIM-3 between primary and metastatic sites in renal cell carcinoma

Abstract

BackgroundDue to the significant heterogeneity of renal cell carcinoma (RCC), immune checkpoints may express differently between primary and metastatic tumor. We aimed to evaluate the differential expression of TIM-3 between the primary and metastatic sites of RCC.MethodsCases of RCC with metastases resected or biopsied at West China Hospital between January 2009 and November 2016 were included. Clinicopathological parameters were retrospectively extracted. SPPS 22.0, GraphPad Prism 6 and R statistical software were applied for data analysis.ResultsA total of 163 cases were included. Immunohistochemical results showed that the overall detection rate of TIM-3 was 56.4% (92/163). The detection rate of TIM-3 in the primary (53.0%, 44/83) was numerically higher than that of the metastasis (42.6%,79/174). Although the concordance rate of TIM-3 between the primary and metastasis was as high as 66.3% (55/83) in the paired cohort, a significant statistically difference of TIM-3 expression between the primary and metastasis was observed (χ2 = 4.664, p = 0.002), with a poor consistency (Kappa = 0.331, p = 0.002). Subsequent survival analysis suggested that TIM-3 expression either in the primary or metastatic tumor was associated with longer progression-free survival (PFS) (HR: 0.67, 95% CI 0.45–0.99, P = 0.02) and overall survival (OS) (HR: 0.52, 95% CI 0.33–0.82, P < 0.001). The expressions of TIM-3 in the primary, metastatic tumors and patients treated with targeted agents all played as favorable factors for PFS and OS. Further multivariate analysis showed that, in the whole cohort, TIM-3 expression in metastatic tumor increased the predicted accuracy (PA) of the whole model of PFS from 74.7 to 75.6% (P = 0.02). For OS, the PA of whole model was increased from 78.1 to 81.1% by adding TIM-3 expression in the metastasis (P = 0.005). The same trends were also observed in paired patients and patients treated with targeted agents. In conclusion, the expression difference between the primary and metastatic tumor of TIM-3 was significant. Biopsy or resection of the metastases may provide a more accurate biological information for clinician’s decision-making and the patient’s prognosis. What’s more, the role of TIM-3 in the RCC still remains controversy, further study are needed to verify the conclusion.

Precision Medical Sciences

“…It was reassuring that high‐level expression of TIM‐3 may be a general poor prognostic biomarker in osteosarcoma, gastric cancer, liver cancer, esophageal cancer and lymphoma. Although some findings suggested that high TIM‐3 expression indicated longer OS in breast cancer (HR = 0.11, 95% CI: 0.03‐0.39) 5 and renal cell carcinoma (HR = 0.54, 95% CI: 0.25‐1.17), 6 we found no relationship between TIM‐3 and breast cancer/kidney cancer/lung cancer. The possible reasons might include: (a) the function of TIM‐3 may vary depending upon tumor stages; (b) due to the heterogeneous nature of cancer 4‐6,55 .…”

“…As shown in Figure 1, the initial literature search obtained 2432 articles and a total of 33 studies, 4‐6,12‐18,26‐48 including 4223 patients were finally included after further examination.…”

“…T‐cell immunoglobulin mucin‐3 (TIM‐3) is mainly localized on the T‐cell surface as an immune checkpoint (co‐inhibitory signal receptor) 3 . Lots of studies demonstrated that TIM‐3 played a pivotal role in immune modulation of cancers 4‐6 . Moreover, previous research showed that aberrant TIM‐3 expression was central to carcinogenesis and progression 7 .…”

“…However, more and more researches have been published to explore the function of TIM‐3 in cancers over the past 5 years, and new evidences have been contrary to previously published studies. Specifically, Burugu et al found that high TIM‐3 expression cancer tissue was associated with good prognosis in patients 4‐6 . Meanwhile, previous research only discussed the prognostic significance of patients' overall survival (OS), 19 and so far, the relationship between high expression of TIM‐3 and certain tumor types remains unclear.…”

Tim-3 promotes cell aggressiveness and paclitaxel resistance through the NF-κB /STAT3 signaling pathway in breast cancer

“…T-cell immunoglobulin and mucin-domain containing molecule-3 (Tim-3), also known as hepatitis A of colorectal cancer cells [20], and low expression level of Tim-3 in prostate cancer tissues is associated with poor prognosis for metastatic prostate cancer patients [21].Tim-3 expression either in primary or metastatic renal cell carcinoma is associated with longer progression-free survival (PFS) and overall survival (OS) [22]. The diverse prognosis significance of Tim-3 suggests that the role of Tim-3 might be dependent on tumour types or Tim-3 distribution.…”