Association of the expression levels of lncRNAs GAS5, HAND2-AS1, LINC00152 and LINC00339 and tumor size with lymphogenous metastasis in clear-cell renal-cell carcinoma

The frequency of clear-cell renal-cell carcinoma (ccRCC) metastasis has reached 25-30%, which makes the search for prognostic biomarkers urgent. Long non-coding RNAs (lncRNAs) regulate biological processes and may serve as prognostic markers. The aim of our study was to compare the expression levels of lncRNAs GAS5, HAND2-AS1, LINC00152 and LINC00339 in tumors and normal kidney tissue and analyze the association of their changes with clinicopathological parameters of ccRCC.

We used archival RNA samples (RIN>7) from 70 primary tumors with a confirmed diagnosis of ccRCC and 70 adjacent normal kidney tissues. Expression analysis was performed by RT-qPCR. Statistical analysis was performed using a multivariate ANOVA test (p ≤ 0.05).

A decrease in the expression of GAS5 by 5.25, HAND2-AS1 by 5.92, LINC00152 by 2.04 and LINC00339 by 2.34 times was revealed in the tumor tissues. The expression of LINC00152 did not change at T1, T2 and T3 (the TNM classification) and decreased by 33.43 times when the tumor grew beyond Gerota’s fascia (T4). LINC00152 expression was lower in T4 tumors compared to tumors of a smaller size: T1/T4—10.86 times; T2/T4—22.76 times; and T3/T4—27.11 times. LINC00152 expression decreased by 4.71 times in cases with multiple lesions of regional lymph nodes (normal/N2), including compared with tumors with no metastases in the lymph nodes (N0/N2) or one affected lymph node (N1/N2), by 4.36 and 7.26 times, respectively. HAND2-AS1 had a lower level of expression in tumors with multiple lesions of regional lymph nodes: normal/N2—15.02 times; N0/N2—5.84 times; N1/N2—4.04 times.

The significant decrease in the expression of HAND2-AS1 and LINC00152 when more than one regional lymph node is affected (N2 according to the TNM classification) in ccRCC allows us to propose them as prognostic markers of lymphogenous metastasis in the absence of the ability to evaluate regional lymph nodes (Nx).