Prognostic value of meta-signature miRNAs in renal cell carcinoma: an integrated miRNA expression profiling analysis

Objective: To identify histopathological and immunophenotypical features with potential predictive or prognostic value in patients undergoing pulmonary metastasectomy from renal cell carcinoma (RCC). Methods: We retrospectively collected all consecutive patients undergoing pulmonary metastasectomy from RCC after prior nephrectomy. Paired samples of primary tumors and corresponding pulmonary metastases were analyzed, revising histopathological features and testing C-MET, mTOR, and PD-L1 by immunohistochemistry. Results: A total of 25 patients were included. Median overall survival (mOS) from metastasectomy was 5.5 years (95% CI = 1.9–9.1). The laterality of metastases had a significant predictive value, with median relapse-free survival (mRFS) from metastasectomy not reached (NR) at mean follow-up (FU) of 60.8 months for left lung involvement, mRFS of 52.9 months (95% CI = 0–145.5) for the right lung and 6.4 months (95% CI = 1.7–11) for bilateral metastases ( p = 0.028). Primary RCC with positive expression of mTOR had higher mOS after metastasectomy than negative cases ( p < 0.001), NR at mean FU of 4.3 years versus mOS of 2 years (95% CI = 0.7–3.3), respectively. PD-L1 positivity on intra-tumor (TILs) and peri-tumor (RILs) infiltrating lymphocytes of metastases was related to higher OS, NR versus 2 years (95% CI = 1.2–2.7, p = 0.003), and NR versus 1.4 years (95% CI = 0.2–2.6, p = 0.012), respectively. The shorter was the surgical interval, the more probably the metastases had high c-MET expression (>70%) ( p = 0.007) and PD-L1 expression >10% on TILs ( p = 0.024). Conclusions: mTOR positivity on primary RCC could be a favorable prognostic factor to select patients for pulmonary metastasectomy. The positive impact of PD-L1 expression on immune cells is opposite to the well-known negative prognostic value of PD-L1 on tumor cells in RCC.

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Prognostic Value of Plasma hPG80 (Circulating Progastrin) in Metastatic Renal Cell Carcinoma

Cancers ◽

10.3390/cancers13030375 ◽

2021 ◽

Vol 13 (3) ◽

pp. 375

Author(s):

Manish Kohli ◽

Winston Tan ◽

Bérengère Vire ◽

Pierre Liaud ◽

Mélina Blairvacq ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Prognostic Value ◽

Risk Model ◽

Predictive Accuracy ◽

Area Under The Curve ◽

Risk Groups ◽

Prognostic Impact ◽

Significant Difference

Precise management of kidney cancer requires the identification of prognostic factors. hPG80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including renal cell carcinoma (RCC). In this study, we evaluated the prognostic value of plasma hPG80 in 143 prospectively collected patients with metastatic RCC (mRCC). The prognostic impact of hPG80 levels on overall survival (OS) in mRCC patients after controlling for hPG80 levels in non-cancer age matched controls was determined and compared to the International Metastatic Database Consortium (IMDC) risk model (good, intermediate, poor). ROC curves were used to evaluate the diagnostic accuracy of hPG80 using the area under the curve (AUC). Our results showed that plasma hPG80 was detected in 94% of mRCC patients. hPG80 levels displayed high predictive accuracy with an AUC of 0.93 and 0.84 when compared to 18–25 year old controls and 50–80 year old controls, respectively. mRCC patients with high hPG80 levels (>4.5 pM) had significantly lower OS compared to patients with low hPG80 levels (<4.5 pM) (12 versus 31.2 months, respectively; p = 0.0031). Adding hPG80 levels (score of 1 for patients having hPG80 levels > 4.5 pM) to the six variables of the IMDC risk model showed a greater and significant difference in OS between the newly defined good-, intermediate- and poor-risk groups (p = 0.0003 compared to p = 0.0076). Finally, when patients with IMDC intermediate-risk group were further divided into two groups based on hPG80 levels within these subgroups, increased OS were observed in patients with low hPG80 levels (<4.5 pM). In conclusion, our data suggest that hPG80 could be used for prognosticating survival in mRCC alone or integrated to the IMDC score (by adding a variable to the IMDC score or by substratifying the IMDC risk groups), be a prognostic biomarker in mRCC patients.

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