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Comprehensive subgroup analyses of survival outcomes between clear cell renal cell adenocarcinoma and papillary renal cell adenocarcinoma.

ABSTRACT: To comprehensively compare the survival outcomes of clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC), the study cohort included ccRCC and pRCC patients in 2004-2017 from the Surveillance, Epidemiology, and End Results (SEER) database, which comprises 18 registries. Primary outcomes including overall mortality (OM) and cancer-specific mortality (CSM) were evaluated. Subgroup analyses were conducted for different ages, race, and disease stages. A total of 112,270 cases were eligible for the current analysis, including 92,209 cases of ccRCC and 20,061 cases of pRCC. Univariate analyses suggested that pRCC has a more favorable outcome than ccRCC in terms of CSM (HR: 0.72, 95% CI: 0.68-0.75, p < 0.001) and OM (HR: 0.90, 95% CI: 0.88-0.93, p < 0.001). Multivariate-adjusted HRs suggested that pRCC has worse survival outcomes than ccRCC (adjusted HR: 1.08 for CSM and 1.05 for OM, both p < 0.05). Subgroup analyses showed that pRCC had a significantly poorer prognosis than ccRCC among patients ?45 years old (HR_CSM : 1.59, 95% CI: 1.31-1.93, p < 0.001; HR_OM : 1.63, 95% CI: 1.40-1.90, p < 0.001). Among patients with distant metastasis, those with pRCC had a higher risk of CSM and OM than those with ccRCC (HR_CSM : 1.28, 95% CI: 1.19-1.39, p < 0.001; HR_OM : 1.30, 95% CI: 1.21-1.40, p < 0.001). Propensity score analyses for patients ?45 years old and those with metastasis showed similar results. The lack of information on pRCC subtypes in the SEER database was a limitation. In conclusion, pRCC has poorer survival outcomes than ccRCC among patients younger than 45 years old and patients with distant metastasis.

SUBMITTER: Huang J

PROVIDER: S-EPMC7774724 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Comprehensive subgroup analyses of survival outcomes between clear cell renal cell adenocarcinoma and papillary renal cell adenocarcinoma.

Huang Jingyi J Huang Da D Yan Jiaqi J Chen Tianhe T Gao Yi Y Xu Danfeng D Na Rong R

Cancer medicine 20201103 24

To comprehensively compare the survival outcomes of clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC), the study cohort included ccRCC and pRCC patients in 2004-2017 from the Surveillance, Epidemiology, and End Results (SEER) database, which comprises 18 registries. Primary outcomes including overall mortality (OM) and cancer-specific mortality (CSM) were evaluated. Subgroup analyses were conducted for different ages, race, and disease stages. A total of 112,270 c ...[more]

PMID: 33141518

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Project description:ImportanceThere exists considerable biological and clinical variability between histologic variants of metastatic renal cell carcinoma (mRCC). Data reporting on patterns of metastasis in histologic variants of mRCC are sparse.ObjectiveTo characterize sites of metastasis and their association with survival across the 3 most common histologic variants of mRCC: clear cell (ccRCC), papillary (pRCC), and chromophobe (chrRCC).Design, setting, and participantsIn this multicenter, international cohort study, the International mRCC Database Consortium (IMDC) database was used to identify consecutive patients starting systemic therapy for mRCC between 2002 and 2019. Patients with mixed histologic subtype were excluded. Statistical analysis was performed from February to June 2020.ExposuresData regarding histologic subtype and sites of metastatic involvement at the time of first systemic therapy initiation were collected.Main outcomes and measuresThe primary outcomes were prevalence of metastatic site involvement and overall survival (OS) from time of systemic therapy initiation. Patients with multiple sites of metastatic involvement were included in analyses of all groups to which they had metastases.ResultsA total of 10 105 patients were eligible for analysis. Median (interquartile range) age at diagnosis was 60 (53-67) years, 7310 (72.4%) were men and 8526 (84.5%) underwent nephrectomy. Of these, 9252 (92%) had ccRCC, 667 (7%) had pRCC, and 186 (2%) had chrRCC. The median number of sites of metastasis was 2 (range, 0-7). In ccRCC, the most common sites of metastasis were lung (70%; 6189 of 8804 patients [448 missing]), lymph nodes (45%; 3874 of 8655 patients [597 missing]), bone (32%; 2847 of 8817 patients [435 missing]), liver (18%; 1560 of 8804 [448 missing]), and adrenal gland (10%; 678 of 6673 patients [2579 missing]). Sites of metastasis varied between subtypes. Lung, adrenal, brain, and pancreatic metastases were more frequent in ccRCC, lymph node involvement was more common in pRCC, and liver metastases were more frequent in chrRCC. Median OS for ccRCC varied by site of metastatic involvement, ranging between 16 months (95% CI, 13.7-18.8 months) for the pleura and 50 months (95% CI, 41.1-55.5 months) for the pancreas. Compared with ccRCC, patients with pRCC tended to have lower OS, regardless of metastatic site.Conclusions and relevanceSites of metastatic involvement differ according to histologic subtype in mRCC and are associated with OS. These data highlight the clinical and biological variability between histologic subtypes of mRCC. Patterns of metastatic spread may reflect differences in underlying disease biology. Further work to investigate differences in immune, molecular, and genetic profiles between metastatic sites and histologic subtypes is encouraged.

Project description:Background: Laminin subunit gamma 1 (LAMC1) protein is associated with tumor cell invasion and metastasis. However, its role in kidney cancer remains unclear. In this work, we sought to probe the expression as well as its carcinogenic mechanisms of LAMC1 in kidney renal papillary cell carcinoma (KIRP) and kidney renal clear cell carcinoma (KIRC). Methods: Public databases including TIMER, Oncomine, UALCAN, TISIDB, TCGA, Kaplan-Meier plotter, UCSC Xena, cBioPortal, SurvivalMeth, KEGG, GeneMANIA, Metascape, GSCALite and GDSC were adopted, and the expression, clinical pathological correlation, prognostic signatures, dominant factors influencing LAMC1 expression, DNA methylation levels, gene mutations, copy number variations, functional networks, and drug sensitivity were analyzed. Expression of LAMC1 protein in clinical KIRP and KIRC was validated using tissue array. Results: LAMC1 expression in KIRP and KIRC were significantly higher than those in normal tissues. High LAMC1 expression indicated poor overall survival in KIRP patients and better overall survival in KIRC patients. Through the univariate and multivariate Cox analysis, we found that high LAMC1 expression was a potential independent marker for poor prognosis in KIRP, however it implied a better prognosis in KIRC by univariate Cox analysis. In addition, the LAMC1 expression in KIRP and KIRC was negatively correlated with methylation levels of LAMC1 DNA. Interestingly, LAMC1 expression was positively correlated with the infiltration of CD8+ T cells, dendritic cells and neutrophils in KIRP; however, it was positively correlated with the infiltration of CD4+ T cells, macrophages and neutrophils but negatively correlated with B cells in KIRC. Moreover, high level of CD8+ T cells is beneficial for KIRC prognosis but opposite for KIRP. LAMC1 may participate in signaling pathways involved in formation of adherens junction and basement membrane in KIRP and KIRC, and the high expression of LAMC1 is resistant to most drugs or small molecules of the Genomics of Drug Sensitivity in Cancer database. Conclusion: Enhanced LAMC1 expression suggests a poor prognosis in KIRP while a better prognosis in KIRC, and these opposite prognostic signatures of LAMC1 may be related to different immune microenvironments.

Dataset Information

Comprehensive subgroup analyses of survival outcomes between clear cell renal cell adenocarcinoma and papillary renal cell adenocarcinoma.

Publications

Comprehensive subgroup analyses of survival outcomes between clear cell renal cell adenocarcinoma and papillary renal cell adenocarcinoma.

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