TMEM27 expression and clinical characteristics and survival in clear cell renal cell carcinoma

Abstract

Background

Transmembrane protein 27 (TMEM27/collectrin), a glycoprotein and homolog of angiotensin-converting enzyme 2 (ACE2), is a regulator of renal amino acid uptake in the proximal tubule and may have a protective role in hypertension. Two previous reports have shown that the absence of TMEM27 expression in clear cell renal cell carcinoma (ccRCC) correlates with poorer cancer-related survival. We report our findings of TMEM27 expression in ccRCC and clinical outcomes in an independent third cohort.

Material and Methods

We conducted a retrospective analysis to identify all 321 cases of ccRCC diagnosed between 2010 and 2015 at the University of Rochester Medical Center. The intensity of TMEM27 immunostaining on tumor tissue was semi-quantitatively graded on a scale of 0, 0.5, 1, 1.5, 2, 2.5, and 3 by a single pathologist, and correlated with tumor characteristics and survival.

Results

There was evidence of metastasis at time of nephrectomy in 36 (11.2%) cases, and at the latest follow-up in 70 (21.8%) cases. As of Spring 2021, 82 (25.5%) had died. TMEM27 staining intensity correlated inversely with various tumor characteristics. Kaplan-Meier survival analysis showed worse overall all-cause mortality (p = 0.02) and disease-free survival (p = 0.028) for tumors without any TMEM27 staining (0) compared to 0.5 or higher by log-rank test.

Conclusion

The absence of TMEM27 expression is associated with more aggressive tumor characteristics and poorer all-cause mortality and disease-free survival in ccRCC. TMEM27 may be a useful biomarker to assess cancer prognosis. Further studies are needed to better assess if TMEM27 is protective in RCC, and its potential role in active surveillance and prediction of response to target therapy.

Keywords:

• Transmembrane protein 27 (TMEM27)
• collectrin
• clear cell renal cell carcinoma

Acknowledgement

The authors are grateful to Sierra Kovar for her excellent technical support and guidance.

Ethical approval

This research was performed under approval of an institutional review board (STUDY00005344) and all ethical principles and guidelines for the protection of human subjects were followed.

Author contributions

THL conceived of and initiated the study. RG and LLR performed the chart review and data collection. HYGC assessed immunostaining and performed the pathology portion of the data collection. DXG performed statistical analysis. RG and THL wrote the first draft of the manuscript. RG, PMR, and THL critically revised the work. TB and LC assisted in slide collection and performed the immunostaining of all case slides. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author, [RG], upon reasonable request.