On 2014 Apr 29, Peter Wilson commented:

In the manuscript the authors incorrectly state that the function of the enzyme thymidylate synthase (TS) is the following:

"TS is a key enzyme that catalyzes the methylation of fluorod UMP, the precursor of DNA synthesis, into dTMP"

This is incorrect. Thymidylate synthase catalyzes the reductive methylation of dUMP (deoxyuridine) to dTMP (thymidine monophosphate; thymidylate). Fluoro-dUMP (or FdUMP as it is more commonly abbreviated to) is a potent fluoropyrimidine-derived irreversible inhibitor of TS and has nothing to do with the enzymatic mechanism of TS or the subject content of this manuscript.

The reference provided for the TS enzymatic mechanism is also not specific to TS whatsoever and the proper terms should be given as well as the abbreviations e.g. thymidine monophosphate (dTMP) and deoxyuridine monophosphate (dUMP).

Since the subject of this manuscript is centered around TS, the enzymatic function should be described accurately and precisely and this should be rectified.

The authors also state: "However, this is the first and initial meta-analysis of assessment whether TS expression is associated with objective response in patients with NSCLC treated with pemetrexed-containing chemotherapy."

This is also incorrect. This study is now the third to address this issue with two previous manuscripts published in 2013. According to the BMC Cancer pre-publication record, both previous manuscripts addressing this issue were published for a significant period of time before the final version of this current paper was submitted by March 5th, 2014 and therefore should have been referenced and discussed appropriately.

Liu Y, Yin TJ, Zhou R, Zhou S, Fan L, Zhang RG. Cancer Chemother Pharmacol. 2013 Nov;72(5):1125-32.

Wang T, Chuan Pan C, Rui Yu J, Long Y, Hong Cai X, De Yin X, Qiong Hao L, Li Luo L. PLoS One. 2013 Sep 10;8(9):e74284. doi: 10.1371/journal.pone.0074284.

On 2014 Apr 29, Peter Wilson commented:

In the manuscript the authors incorrectly state that the function of the enzyme thymidylate synthase (TS) is the following:

"TS is a key enzyme that catalyzes the methylation of fluorod UMP, the precursor of DNA synthesis, into dTMP"

This is incorrect. Thymidylate synthase catalyzes the reductive methylation of dUMP (deoxyuridine) to dTMP (thymidine monophosphate; thymidylate). Fluoro-dUMP (or FdUMP as it is more commonly abbreviated to) is a potent fluoropyrimidine-derived irreversible inhibitor of TS and has nothing to do with the enzymatic mechanism of TS or the subject content of this manuscript.

The reference provided for the TS enzymatic mechanism is also not specific to TS whatsoever and the proper terms should be given as well as the abbreviations e.g. thymidine monophosphate (dTMP) and deoxyuridine monophosphate (dUMP).

Since the subject of this manuscript is centered around TS, the enzymatic function should be described accurately and precisely and this should be rectified.

The authors also state: "However, this is the first and initial meta-analysis of assessment whether TS expression is associated with objective response in patients with NSCLC treated with pemetrexed-containing chemotherapy."

This is also incorrect. This study is now the third to address this issue with two previous manuscripts published in 2013. According to the BMC Cancer pre-publication record, both previous manuscripts addressing this issue were published for a significant period of time before the final version of this current paper was submitted by March 5th, 2014 and therefore should have been referenced and discussed appropriately.

Liu Y, Yin TJ, Zhou R, Zhou S, Fan L, Zhang RG. Cancer Chemother Pharmacol. 2013 Nov;72(5):1125-32.

Wang T, Chuan Pan C, Rui Yu J, Long Y, Hong Cai X, De Yin X, Qiong Hao L, Li Luo L. PLoS One. 2013 Sep 10;8(9):e74284. doi: 10.1371/journal.pone.0074284.