Genetic landscape of prognostic value in pancreas ductal adenocarcinoma microenvironment—reply
Letter to the Editor

Genetic landscape of prognostic value in pancreas ductal adenocarcinoma microenvironment—reply

Ning Pu1,2, Jun Yu2*, Wenchuan Wu1*

1Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; 2Department of Surgery and The Pancreatic Cancer Precision Medicine Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA

*These authors shared the co-senior authors.

Correspondence to: Wenchuan Wu, MD, PhD. Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China. Email: wu.wenchuan@zs-hospital.sh.cn; Jun Yu, MD, PhD. Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD, 21287, USA. Email: jyu41@jhmi.edu.

Provenance and Peer Review: This article was commissioned by the editorial office, Annals of Translational Medicine. The article did not undergo external peer review.

Response to: Williams MH, Mahadevan D. In Silico analyses of host immunity and stroma provide prognostic factors in early stage pancreatic ductal adenocarcinoma (PDAC). Ann Transl Med 2020;8:259.
Mishra NK, Southekal S, Guda C. Prognostic value of biomarkers in the tumor microenvironment of pancreatic ductal adenocarcinoma. Ann Transl Med 2020. doi: 10.21037/atm.2020.03.59


Submitted Mar 17, 2020. Accepted for publication Apr 01, 2020.

doi: 10.21037/atm.2020.04.30


Thank you for the constructive editorial commentaries on our recently published research, “Genetic landscape of prognostic value in pancreatic ductal adenocarcinoma microenvironment” (1).

In the editorial commentary “Prognostic value of biomarkers in the tumor microenvironment of pancreatic ductal adenocarcinoma”, Mishra et al., showed the experiences of their previous researches and other publications, which was consistent with our research. They also did great work on identifying the novel and potential prognostic markers of pancreatic ductal adenocarcinoma (PDAC), such as three genes (B3GNT3, DMBT1, and DEPDC1B), two long non-coding RNA (PVT1 and GATA6-AS), and 406 promoter methylation target loci, which were strongly correlated with survival (2). Their results provided positive feedback to our novel findings, and hoped to apply data from other public cohorts to establish the role of genes associated with higher immune and stromal scores in in-vivo, in-vitro, and PDAC patient samples.

In another recent commentary, Williams et al., presented that “In Silico analyses of host immunity and stroma provide prognostic factors in early-stage pancreatic ductal adenocarcinoma (PDAC)”. We agree that CA19-9 may help stratify patients to immune/stroma subtypes. Previous publications have demonstrated that CA19-9 is considered as a prognostic indicator in pancreatic cancer patients (3-5). Regrettably, no CA19-9 data was able to be retrieved from the database. We want to collect our samples to validate our observations, and then we can further analyze the correlations with CA19-9. In addition, they mentioned that a major limitation of our study was the lack of tumor microenvironment (TME) data from patients with advanced disease, with only 5% of the study population having stage III or IV disease. That’s absolutely correct and the cases used in our cohort were all underwent surgical resection. Obvious advanced diseases confirmed by the image do not fit the criteria of the surgery. Furthermore, the first choice of the treatment for PDAC with metastatic disease is usually chemoradiotherapy (6). Locally advanced diseases or occasional occult metastatic disease underwent surgery, like those 5% of stage III/IV diseases in the cohort, does exist in clinic based on the surgeon with aggressive surgery, such as at our institution at Johns Hopkins Hospital. On the other hand, there was a bias for TME in resectable disease majorly. There is a need to investigate the TME data from patients with advanced disease using fine needle biopsies.

Another limitation was the lack of information regarding the cellularity of the tumor and its heterogeneity, contributions of genomic instability to disease heterogeneity, and the issue of low tumor cellularity when compared to the stroma, which were mentioned in the publication. It’s been published that cellular heterogeneity, fibroblast heterogeneity, immune heterogeneity, and genomic heterogeneity all play a vital role in pancreatic cancer progression and metastasis (7-10). Single-cell sequencing, on the other hand, can help conquer all the limitations listed above.

Our study listed numerous genes with prognostic value in the microenvironment of PDAC from functional enrichment analysis. These genes can become auxiliary prognostic biomarkers for PDAC, and further investigation may be valuable to understand the crosstalk between tumor and microenvironment.


Acknowledgments

Funding: None.


Footnote

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm.2020.04.30). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.


References

  1. Pu N, Chen Q, Gao S, et al. Genetic landscape of prognostic value in pancreatic ductal adenocarcinoma microenvironment. Ann Transl Med 2019;7:645. [Crossref] [PubMed]
  2. Mishra NK, Southekal S, Guda C. Survival Analysis of Multi-Omics Data Identifies Potential Prognostic Markers of Pancreatic Ductal Adenocarcinoma. Front Genet 2019;10:624. [Crossref] [PubMed]
  3. Pu N, Gao S, Xu Y, et al. Alkaline Phosphatase-To-Albumin Ratio as a Prognostic Indicator in Pancreatic Ductal Adenocarcinoma after Curative Resection. J Cancer 2017;8:3362-70. [Crossref] [PubMed]
  4. Tingle SJ, Severs GR, Goodfellow M, et al. NARCA: A novel prognostic scoring system using neutrophil-albumin ratio and Ca19-9 to predict overall survival in palliative pancreatic cancer. J Surg Oncol 2018;118:680-6. [Crossref] [PubMed]
  5. Asaoka T, Miyamoto A, Maeda S, et al. Prognostic impact of preoperative NLR and CA19-9 in pancreatic cancer. Pancreatology 2016;16:434-40. [Crossref] [PubMed]
  6. Diener MK, Combs SE, Büchler MW. Chemoradiotherapy for locally advanced pancreatic cancer. Lancet Oncol 2013;14:269-70. [Crossref] [PubMed]
  7. Helms E, Onate MK, Sherman MH. Fibroblast Heterogeneity in the Pancreatic Tumor Microenvironment. Cancer Discov 2020. [Epub ahead of print]. [Crossref] [PubMed]
  8. Li X, Bean A, Uehara M, et al. Immune heterogeneity of head and tail pancreatic lymph nodes in non-obese diabetic mice. Sci Rep 2019;9:9778. [Crossref] [PubMed]
  9. Lawlor N, Stitzel ML. (Epi)genomic heterogeneity of pancreatic islet function and failure in type 2 diabetes. Mol Metab 2019;27S:S15-24. [Crossref] [PubMed]
  10. Hosein AN, Huang H, Wang Z, et al. Cellular heterogeneity during mouse pancreatic ductal adenocarcinoma progression at single-cell resolution. JCI Insight 2019. [Crossref] [PubMed]
Cite this article as: Pu N, Yu J, Wu W. Genetic landscape of prognostic value in pancreas ductal adenocarcinoma microenvironment—reply. Ann Transl Med 2020;8(9):599. doi: 10.21037/atm.2020.04.30