Tissue and urinary KIM-1 relate to tumor characteristics in patients with clear renal cell carcinoma

Abstract

The objective of this prospective follow-up trial was to ascertain whether the urinary kidney injury molecule-1 (uKIM-1) associates with tumor tissue (tKIM-1) expression and with the pathological characteristics of clear renal cell carcinoma (cRCC) in radically nephrectomized (RN) and/or in partially nephrectomized (PN) patients with cRCC, pre- and postoperatively. This clinical study included 40 patients subjected to RN/PN (cRCC group) and 30 healthy volunteers (control group). Urinary KIM-1 was determined by ELISA TIM-1/KIM-1 kit and normalized by urinary creatinine. Immunohistochemical staining (monoclonal anti-human anti-TIM-1/KIM-1/HAVCR antibody) was used for semiquantitative analysis of the tKIM-1 expression and expressed as a score (% KIM-1 positively stained tubules). Both markers were interpreted in terms of the tumor characteristics comprising tumor size, Fuhrman grade, pathological (pT) stage, tumor/nodes/metastasis (TNM) stage, lymphovascular invasion and type of surgery RN/PN. Preoperative uKIM-1 was significantly higher in the cRCC group compared to controls, such as uKIM-1 was statistically higher in RN than in PN patients. Postoperatively, uKIM-1 decreased to control values. Expression of tKIM-1 was documented in all nephrectomized patients. Significant associations were achieved between uKIM-1 and tKIM-1 and with considered tumor characteristics, especially with tumor size and grade. Based on the accomplished associations, we found uKIM-1 as a highly sensitive marker for cRCC diagnosis. The clinical trial registration number: 1110-2012.

Prognostic value of TIM-1 expression in human non-small-cell lung cancer

“…Of note, some data also demonstrate that TIM-1 may have a novel function as part of the regulatory apparatus for tight junction of endothelial cells [28]. Moreover, increased TIM-1 expression is also found in certain human cancer tissues, such as gastric cancer, clear renal cell carcinoma, LCS, primary central nervous system lymphoma, colorectal cancer and so on, and the expression level of TIM-1 in cancer tissues or cancer cells is significantly correlated with cancer progression and survival of the patients [19–21, 29, 30]. Interestingly, some data have also reported that activation of TIM-1 signaling by using TIM-4 fusion protein can lead to the cell apoptosis in colon cancer cells, suggesting a different role of TIM-1 in defining cell fate of cancer cells [31].…”

“…Liu et al [20] have also reported that increased TIM-1 expression is found in human gastric cancer tissues compared with the normal gastric tissues at both the mRNA and protein levels, and high expression of TIM-1 can serve as a novel prognostic factor for gastric cancer. Moreover, urinary TIM-1 can also be found in patients with clear renal cell carcinoma, and its expression is significantly correlated with tumor characteristics [21].…”

KIM-1 as a potential serological/urinological tumor-associated marker of renal cell carcinoma and chemotherapy nephrotoxicity

“…Опыт использования KIM-1 как опухолеассоциированного маркера почечноклеточного рака В ряде исследований было показано, что при ПКР определенных гистологических типов уровни KIM-1 в моче и / или плазме крови (uKIM-1 и pKIM-1 соответственно) возрастают [15,16,[41][42][43]. Количество таких работ пока невелико, однако они обусловливают актуальность изучения маркера в аспекте активного выявления, уточняющей диагностики и мониторинга эффективности лечения больных с этим заболеванием.…”

“…Подтверждение повышенной экспрессии uKIM-1 у больных ПКР продемонстрировано еще в одном исследовании, включившем 40 больных ПКР с планируемой нефрэктомией или резекцией почки, а также 30 здоровых добровольцев (контрольная группа) [42]. Уровень uKIM-1 также нормализовали по концентрации креатинина.…”

“…Концентрации uKIM-1 статистически значимо коррелировали с размером опухоли и ее степенью дифференцировки. Таким образом, авторы сделали вывод о том, что uKIM-1 является высокочувствительным маркером, который может быть использован в клинической практике, в уточняющей диагностике ПКР, а также для определения прогноза заболевания [42].…”