The expression of Wnt-1 inducible signaling pathway protein-2 in astrocytoma: Correlation between pathological grade and clinical outcome
Authors: Zhi Tang
Zhiping Zhang
Xianrui Yuan
Gelei Xiao
Zhengwen He
Jian Yuan
Jie Zhao
Jingping Liu
Journal: Oncology Letters (2015)
Discipline: CLINICAL MEDICINE
Keywords: Wnt-1 inducible signaling pathway protein-2; astrocytoma; overall survival; progression-free survival.
Affiliations: The Institute of Skull Base Surgery and Neurooncology at Hunan, Xiangya Hospital, Changsha, Hunan 410008, P.R. China., Department of Neurosurgery, Hunan Provincial Tumor Hospital, The Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, P.R. China.

Abstract:  Wnt-1 inducible signaling pathway protein-2 (WISP-2) is a member of the CCN family, which is critical for the control of cell morphology, motion, adhesion and other processes involved in tumorigenesis. The expression pattern and clinical significance of WISP-2 in astrocytomas remains unclear. In this study, reverse transcription-polymerase chain reaction was performed to systematically investigate the expression of WISP-2 in 47 astrocytoma tissues of different pathological grades and 10 normal brain tissues. The mRNA expression levels of WISP-2 in the astrocytoma tissues were observed to be significantly higher than those in the normal brain tissues. Furthermore, the upregulation of WISP-2 was found to be associated with astrocytomas of higher pathological grades. Subsequently, 154 astrocytoma and 15 normal brain tissues were analyzed using immunohistochemistry and similar results were obtained. Univariate and multivariate survival analyses were used to determine the correlations between WISP-2 expression and overall survival (OS) and progression-free survival (PFS). The results indicated that the expression of WISP-2 was found to negatively correlate with patient PFS and OS. These results demonstrated that the WISP-2 protein is involved in the pathogenesis and progression of human astrocytomas and may serve as a malignant biomarker of this disease. 

Retracted: No

PubPeer comments:
 1. Materials and methods-Tissue samples said 14 normal brain paraffin-embedded samples used, but in Table I, it became 15 normal brain tissue. 2. In table I, the means of WHO I, II, III, IV tumor were all lower than the mean of Astrocytomas. But obviously Astrocytomas were composed by WHO I, II, III, IV tumors.... same happened in tumor size....... 3. In table I, there should be 23 grade I + 49 grade II + 57 grade III + 26 grade IV = 155 astrocytomas, but the table said it was 154...... 4. The WISP-2 product size given by primer-blast was 496bp. This study said 155, not sure if it is correct. 5. In table II, the mean calculation was not correct. 47*0.677-9*0.417-17*0.634-15*0.829-6*0.941=-0.793 , 
 Dear Gracila Albomarginatauff1a Thank you for your comments! We have replied the comments carefully and made corresponding correction. The main corrections in the paper and the responds to the comments are as flowing: 1.tMaterials and methods-Tissue samples said 14 normal brain paraffin-embedded samples used, but in Table I, it became 15 normal brain tissue. RESPONSE: Thank you! This is our transcription error. The actual number of specimens is 15, which is modified to 15 in the materials and methods. We have submitted Corrigendum to the magazine. 2.tIn table I, the means of WHO I, II, III, IV tumor were all lower than the mean of Astrocytomas. But obviously Astrocytomas were composed by WHO I, II, III, IV tumors.... same happened in tumor size....... RESPONSE: Thank you! This is our calculation error. The actual means of astrocytomas is 0.650 u00b1 0.138. We have submitted Corrigendum to the magazine. 3.tIn table I, there should be 23 grade I + 49 grade II + 57 grade III + 26 grade IV = 155 astrocytomas, but the table said it was 154...... RESPONSE: Thank you! This is our transcription error. The actual number of astrocytomas of WHO I is 22, which is modified to 22 in the table I. We have submitted Corrigendum to the magazine. 4.tThe WISP-2 product size given by primer-blast was 496bp. This study said 155, not sure if it is correct. RESPONSE: Thank you! The WISP-2 product size was 155bp, this is right. The following documents can be used for supporting: (1)tBanerjee S, Saxena N, Sengupta K, et al. WISP-2 gene in human breast cancer: estrogen and progesterone inducible expression and regulation of tumor cell proliferation. Neoplasia 2003;5:63-73. See in figure 1 u201cThe predictive PCR-product size of WISP-2 is 155 bpu201d 5.tIn table II, the mean calculation was not correct. 470.677-90.417-170.634-150.829-6*0.941=-0.793 RESPONSE: Thank you! This is our calculation error. The actual means of astrocytomas is 0.694 u00b1 0.445. We have submitted Corrigendum to the magazine. Best wishes! Gelei Xiao Email:xiaogelei@csu.edu.cn , 
 ![file] Figure 1 RT-PCR analyses of WISP-2 mRNA expression in normal and tumor samples of human breast. Lanes 1u20134, the representative biopsy samples of human breast tumor; Lanes 5 and 7, the representative biopsy samples of non-neoplastic breast adjacent to the tumors; Lanes 6 and 8, the representative biopsy samples of normal breast. Lane M, DNA markers. The representative RT-PCR of GAPDH mRNA exhibiting the quality of RNA. **The predictive PCR-product size of WISP-2 is 155 bp** and that of GAPDH is 114 bp. Reference: Banerjee S, Saxena N, Sengupta K, et al. WISP-2 gene in human breast cancer: estrogen and progesterone inducible expression and regulation of tumor cell proliferation. Neoplasia 2003;5:63-73. , 
 #2 Hello Dr. Xiao, thanks for quick response and letter to magazine. I am sorry for the late reply due to time zone problem. For question 4, there are some facts: 1. Your study used different primer with Banerjee s, the results were not comparable. Your WISP-2 primer was: Forward, TTTCTGGCCTTGTCTCTTCC-3u2032 and reverse, 5u2032-GTGTGTGTAGGCAGGGAGTG. Banerjee study was: 5u2032-CCTACACACACAGCCTATATC (Forward) and 5u2032-CCTTCTCTTCATCCTACCC-3u2032 (Reverse). Different primer would cause different PCR product. So this reference doesn t explain the problem. 2. The Primer-Blast result of Banerjee s study is 155bp, which is correlated with their statement. The Primer-Blast result of your study is 496bp, which is not correlated with your statement. You may use the Blast tool via link https: www.ncbi.nlm.nih.gov tools primer-blast index.cgi The gel result in my lab also showed different result. , 
 Also, as you mentioned in Banerjee s study, they stated:  The predictive PCR-product size of WISP-2 is 155 bp and that of GAPDH is 114 bp . In your study, the PRC-product size of GAPDH was 400bp. Would you mind explaining the difference? , 
 Corrigendum [10 May 2021] . ----------------------------- Subsequently to the publication of the above paper, an interested reader brought to the readersu2019 attention that some statements and primer sequences in the paper had apparently been presented incorrectly. The authors have considered the queries raised by the reader, and acknowledge that there were errors featured in the text of the paper and in the two Tables that are in need of correction; therefore, they wish to publish a corrigendum to rectify these issues. First, the opening sentence of the u201cTissue slidesu201d subsection of the Materials and methods section, in the left-hand column on p. 236, incorrectly stated that the number of normal brain paraffin-embedded samples was 14; the actual number of normal specimens was 15, in agreement with what was written in Table I. Secondly, in Table I on p. 237, the means of astrocytomas was calculated incorrectly, and the actual mean should have been written as 0.650 u00b1 0.138 (instead of 0.986u00b10.138); also, the actual number of astrocytomas of pathological grade WHO I in Table I should have been written as 22, not 23. Thirdly, in Table II on p. 238, the mean of astrocytomas was likewise presently incorrectly owing to a calculation error: This should have been written as 0.694 u00b1 0.445 (instead of 0.677 u00b1 0.445). Finally, the primer sequences for human WISP-2 cDNA were reported incorrectly on p. 236; these should have been written as follows: Forward primer, 5u2032-TTTCTGGCCTTGTCTCTTCC-3u2032 and reverse primer, 5u2032-GCACAGGCGGCGCTGGGTCTC-3u2032. Note that these errors do not affect the stated conclusions of the paper. The authors are grateful to the Editor of *Oncology Letters* for allowing them the opportunity to publish this corrigendum, thank the reader of their article for drawing these errors to their attention, and apologize to the readership for any confusion caused. ,