Title: Phosphoserine Phosphatase as a prognostic biomarker in patients with gastric cancer and
its potential association with immune cells
Version: 0 Date: 20 Sep 2021
Reviewer:  Maikel Peppelenbosch
Reviewer's report:
- Although well intelligible, the text could do with a (further) proofread.
- The introduction would benefit from a short summary of current clinical management
on the development and prevention/treatment  of [early] gastric cancer, before noting that
gastric cancer is still a leading cause of cancer-related death, e.g, by refering to a recent
guideline (Shah SC, Piazuelo MB, Kuipers EJ, Li D. AGA Clinical Practice Update on the
Diagnosis and Management of Atrophic Gastritis: Expert Review. Gastroenterology. 2021
Aug 25:S0016-5085(21)03236-4. doi: 10.1053/j.gastro.2021.06.078) and review  (Waddingham
W, Nieuwenburg SAV, Carlson S, Rodriguez-Justo M, Spaander M, Kuipers EJ, Jansen M,
Graham DG, Banks M. Recent advances in the detection and management of early gastric
cancer and its precursors. Frontline Gastroenterol. 2020 Jul 30;12(4):322-331. doi: 10.1136/
flgastro-2018-101089).
- How specificity of PSPH staining was ascertained is not clear from the manuscript.
- It is unclear whether wether one-sided or two-sided statistical testing was performed
- Discussion: specific types of gastric cancer are characterised by differential sensitivity to
immunotherapy (Kodach LL, Peppelenbosch MP. Targeting the Myeloid-Derived Suppressor
Cell Compartment for Inducing Responsiveness to Immune Checkpoint Blockade Is Best
Limited to Specific Subtypes of Gastric Cancers. Gastroenterology. 2021 Aug;161(2):727. doi:
10.1053/j.gastro.2021.03.047) and may also display different levels of PSPH expression. This
should be discussed.
- Discussion: mechanistic discussion on how PSPH interacts with gastric cancer cell
physioliology should be included. PSPH is clearly implicated in autophagy (Zhang J, Wang E,
Zhang L, Zhou B.. PSPH induces cell autophagy and promotes cell proliferation and invasion
in the hepatocellular carcinoma cell line Huh7 via the AMPK/mTOR/ULK1 signaling pathway.
Cell Biol Int. 2021 Feb;45(2):305-31) which is important in gastric cell physiology and the
interaction with Helicobacter, as evident from genetic polymorphisms in the population that
predispose to the disease (Mommersteeg MC, Yu J, Peppelenbosch MP, Fuhler GM. Genetic
host factors in Helicobacter pylori-induced carcinogenesis: Emerging new paradigms. Biochim
Biophys Acta Rev Cancer. 2018 Jan;1869(1):42-52. doi: 10.1016/j.bbcan.2017.11.00).
Title: Phosphoserine Phosphatase as a prognostic biomarker in patients with gastric cancer and
its potential association with immune cells
Version: 0 Date: 20 Sep 2021
Reviewer:  Maikel Peppelenbosch
Reviewer's report:
- Although well intelligible, the text could do with a (further) proofread.
- The introduction would benefit from a short summary of current clinical management
on the development and prevention/treatment  of [early] gastric cancer, before noting that
gastric cancer is still a leading cause of cancer-related death, e.g, by refering to a recent
guideline (Shah SC, Piazuelo MB, Kuipers EJ, Li D. AGA Clinical Practice Update on the
Diagnosis and Management of Atrophic Gastritis: Expert Review. Gastroenterology. 2021
Aug 25:S0016-5085(21)03236-4. doi: 10.1053/j.gastro.2021.06.078) and review  (Waddingham
W, Nieuwenburg SAV, Carlson S, Rodriguez-Justo M, Spaander M, Kuipers EJ, Jansen M,
Graham DG, Banks M. Recent advances in the detection and management of early gastric
cancer and its precursors. Frontline Gastroenterol. 2020 Jul 30;12(4):322-331. doi: 10.1136/
flgastro-2018-101089).
- How specificity of PSPH staining was ascertained is not clear from the manuscript.
- It is unclear whether wether one-sided or two-sided statistical testing was performed
- Discussion: specific types of gastric cancer are characterised by differential sensitivity to
immunotherapy (Kodach LL, Peppelenbosch MP. Targeting the Myeloid-Derived Suppressor
Cell Compartment for Inducing Responsiveness to Immune Checkpoint Blockade Is Best
Limited to Specific Subtypes of Gastric Cancers. Gastroenterology. 2021 Aug;161(2):727. doi:
10.1053/j.gastro.2021.03.047) and may also display different levels of PSPH expression. This
should be discussed.
- Discussion: mechanistic discussion on how PSPH interacts with gastric cancer cell
physioliology should be included. PSPH is clearly implicated in autophagy (Zhang J, Wang E,
Zhang L, Zhou B.. PSPH induces cell autophagy and promotes cell proliferation and invasion
in the hepatocellular carcinoma cell line Huh7 via the AMPK/mTOR/ULK1 signaling pathway.
Cell Biol Int. 2021 Feb;45(2):305-31) which is important in gastric cell physiology and the
interaction with Helicobacter, as evident from genetic polymorphisms in the population that
predispose to the disease (Mommersteeg MC, Yu J, Peppelenbosch MP, Fuhler GM. Genetic
host factors in Helicobacter pylori-induced carcinogenesis: Emerging new paradigms. Biochim
Biophys Acta Rev Cancer. 2018 Jan;1869(1):42-52. doi: 10.1016/j.bbcan.2017.11.00).
Please review this paper.
user
Title: Phosphoserine Phosphatase as a prognostic biomarker in patients with gastric cancer and
its potential association with immune cells
Version: 0 Date: 20 Sep 2021
Reviewer:  Maikel Peppelenbosch
Reviewer's report:
- Although well intelligible, the text could do with a (further) proofread.
- The introduction would benefit from a short summary of current clinical management
on the development and prevention/treatment  of [early] gastric cancer, before noting that
gastric cancer is still a leading cause of cancer-related death, e.g, by refering to a recent
guideline (Shah SC, Piazuelo MB, Kuipers EJ, Li D. AGA Clinical Practice Update on the
Diagnosis and Management of Atrophic Gastritis: Expert Review. Gastroenterology. 2021
Aug 25:S0016-5085(21)03236-4. doi: 10.1053/j.gastro.2021.06.078) and review  (Waddingham
W, Nieuwenburg SAV, Carlson S, Rodriguez-Justo M, Spaander M, Kuipers EJ, Jansen M,
Graham DG, Banks M. Recent advances in the detection and management of early gastric
cancer and its precursors. Frontline Gastroenterol. 2020 Jul 30;12(4):322-331. doi: 10.1136/
flgastro-2018-101089).
- How specificity of PSPH staining was ascertained is not clear from the manuscript.
- It is unclear whether wether one-sided or two-sided statistical testing was performed
- Discussion: specific types of gastric cancer are characterised by differential sensitivity to
immunotherapy (Kodach LL, Peppelenbosch MP. Targeting the Myeloid-Derived Suppressor
Cell Compartment for Inducing Responsiveness to Immune Checkpoint Blockade Is Best
Limited to Specific Subtypes of Gastric Cancers. Gastroenterology. 2021 Aug;161(2):727. doi:
10.1053/j.gastro.2021.03.047) and may also display different levels of PSPH expression. This
should be discussed.
- Discussion: mechanistic discussion on how PSPH interacts with gastric cancer cell
physioliology should be included. PSPH is clearly implicated in autophagy (Zhang J, Wang E,
Zhang L, Zhou B.. PSPH induces cell autophagy and promotes cell proliferation and invasion
in the hepatocellular carcinoma cell line Huh7 via the AMPK/mTOR/ULK1 signaling pathway.
Cell Biol Int. 2021 Feb;45(2):305-31) which is important in gastric cell physiology and the
interaction with Helicobacter, as evident from genetic polymorphisms in the population that
predispose to the disease (Mommersteeg MC, Yu J, Peppelenbosch MP, Fuhler GM. Genetic
host factors in Helicobacter pylori-induced carcinogenesis: Emerging new paradigms. Biochim
Biophys Acta Rev Cancer. 2018 Jan;1869(1):42-52. doi: 10.1016/j.bbcan.2017.11.00).
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