Differential Spatial Gene and Protein Expression Associated with Recurrence Following Chemoradiation for Localized Anal Squamous Cell Cancer

Sharia Hernandez; Prajnan Das; Emma B. Holliday; Li Shen; Wei Lu; Benny Johnson; Craig A. Messick; Cullen M. Taniguchi; John Skibber; Ethan B. Ludmir; Y. Nancy You; Grace Li Smith; Brian Bednarski; Larisa Kostousov; Eugene J. Koay; Bruce D. Minsky; Matthew Tillman; Shaelynn Portier; Cathy Eng; Albert C. Koong; George J. Chang; Wai Chin Foo; Jing Wang; Luisa Solis Soto; Van K. Morris

doi:10.3390/cancers15061701

Differential Spatial Gene and Protein Expression Associated with Recurrence Following Chemoradiation for Localized Anal Squamous Cell Cancer

Sharia Hernandez, Prajnan Das, Emma B. Holliday, Li Shen, Wei Lu, Benny Johnson, Craig A. Messick, Cullen M. Taniguchi, John Skibber, Ethan B. Ludmir, Y. Nancy You, Grace Li Smith, Brian Bednarski, Larisa Kostousov, Eugene J. Koay, Bruce D. Minsky, Matthew Tillman, Shaelynn Portier, Cathy Eng, Albert C. KoongGeorge J. Chang, Wai Chin Foo, Jing Wang, Luisa Solis Soto, Van K. Morris

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4 Scopus citations

Abstract

The identification of transcriptomic and protein biomarkers prognosticating recurrence risk after chemoradiation of localized squamous cell carcinoma of the anus (SCCA) has been limited by a lack of available fresh tissue at initial presentation. We analyzed archival FFPE SCCA specimens from pretreatment biopsies prior to chemoradiation for protein and RNA biomarkers from patients with localized SCCA who recurred (N = 23) and who did not recur (N = 25). Tumor cells and the tumor microenvironment (TME) were analyzed separately to identify biomarkers with significantly different expression between the recurrent and non-recurrent groups. Recurrent patients had higher mean protein expression of FoxP3, MAPK-activation markers (BRAF, p38-MAPK) and PI3K/Akt activation (phospho-Akt) within the tumor regions. The TME was characterized by the higher protein expression of immune checkpoint biomarkers such as PD-1, OX40L and LAG3. For patients with recurrent SCCA, the higher mean protein expression of fibronectin was observed in the tumor and TME compartments. No significant differences in RNA expression were observed. The higher baseline expression of immune checkpoint biomarkers, together with markers of MAPK and PI3K/Akt signaling, are associated with recurrence following chemoradiation for patients with localized SCCA. These data provide a rationale towards the application of immune-based therapeutic strategies to improve curative-intent outcomes beyond conventional therapies for patients with SCCA.

Original language	English (US)
Article number	1701
Journal	Cancers
Volume	15
Issue number	6
DOIs	https://doi.org/10.3390/cancers15061701
State	Published - Mar 2023

Keywords

chemoradiation
digital spatial profiling
protein profiling
recurrence
squamous anal cell carcinoma

ASJC Scopus subject areas

Oncology
Cancer Research

MD Anderson CCSG core facilities

Bioinformatics Shared Resource

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10.3390/cancers15061701

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Hernandez, S., Das, P., Holliday, E. B., Shen, L., Lu, W., Johnson, B., Messick, C. A., Taniguchi, C. M., Skibber, J., Ludmir, E. B., You, Y. N., Smith, G. L., Bednarski, B., Kostousov, L., Koay, E. J., Minsky, B. D., Tillman, M., Portier, S., Eng, C., ... Morris, V. K. (2023). Differential Spatial Gene and Protein Expression Associated with Recurrence Following Chemoradiation for Localized Anal Squamous Cell Cancer. Cancers, 15(6), Article 1701. https://doi.org/10.3390/cancers15061701

Hernandez, S , Das, P , Holliday, EB , Shen, L , Lu, W, Johnson, B, Messick, CA, Taniguchi, CM, Skibber, J , Ludmir, EB , You, YN , Smith, GL , Bednarski, B, Kostousov, L, Koay, EJ, Minsky, BD, Tillman, M, Portier, S, Eng, C, Koong, AC , Chang, GJ , Foo, WC, Wang, J, Soto, LS & Morris, VK 2023, 'Differential Spatial Gene and Protein Expression Associated with Recurrence Following Chemoradiation for Localized Anal Squamous Cell Cancer', Cancers, vol. 15, no. 6, 1701. https://doi.org/10.3390/cancers15061701

@article{4aeb86669ede4d618e8bd462275af585,

title = "Differential Spatial Gene and Protein Expression Associated with Recurrence Following Chemoradiation for Localized Anal Squamous Cell Cancer",

abstract = "The identification of transcriptomic and protein biomarkers prognosticating recurrence risk after chemoradiation of localized squamous cell carcinoma of the anus (SCCA) has been limited by a lack of available fresh tissue at initial presentation. We analyzed archival FFPE SCCA specimens from pretreatment biopsies prior to chemoradiation for protein and RNA biomarkers from patients with localized SCCA who recurred (N = 23) and who did not recur (N = 25). Tumor cells and the tumor microenvironment (TME) were analyzed separately to identify biomarkers with significantly different expression between the recurrent and non-recurrent groups. Recurrent patients had higher mean protein expression of FoxP3, MAPK-activation markers (BRAF, p38-MAPK) and PI3K/Akt activation (phospho-Akt) within the tumor regions. The TME was characterized by the higher protein expression of immune checkpoint biomarkers such as PD-1, OX40L and LAG3. For patients with recurrent SCCA, the higher mean protein expression of fibronectin was observed in the tumor and TME compartments. No significant differences in RNA expression were observed. The higher baseline expression of immune checkpoint biomarkers, together with markers of MAPK and PI3K/Akt signaling, are associated with recurrence following chemoradiation for patients with localized SCCA. These data provide a rationale towards the application of immune-based therapeutic strategies to improve curative-intent outcomes beyond conventional therapies for patients with SCCA.",

keywords = "chemoradiation, digital spatial profiling, protein profiling, recurrence, squamous anal cell carcinoma",

author = "Sharia Hernandez and Prajnan Das and Holliday, {Emma B.} and Li Shen and Wei Lu and Benny Johnson and Messick, {Craig A.} and Taniguchi, {Cullen M.} and John Skibber and Ludmir, {Ethan B.} and You, {Y. Nancy} and Smith, {Grace Li} and Brian Bednarski and Larisa Kostousov and Koay, {Eugene J.} and Minsky, {Bruce D.} and Matthew Tillman and Shaelynn Portier and Cathy Eng and Koong, {Albert C.} and Chang, {George J.} and Foo, {Wai Chin} and Jing Wang and Soto, {Luisa Solis} and Morris, {Van K.}",

note = "Publisher Copyright: {\textcopyright} 2023 by the authors.",

year = "2023",

month = mar,

doi = "10.3390/cancers15061701",

language = "English (US)",

volume = "15",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "6",

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TY - JOUR

T1 - Differential Spatial Gene and Protein Expression Associated with Recurrence Following Chemoradiation for Localized Anal Squamous Cell Cancer

AU - Hernandez, Sharia

AU - Das, Prajnan

AU - Holliday, Emma B.

AU - Shen, Li

AU - Lu, Wei

AU - Johnson, Benny

AU - Messick, Craig A.

AU - Taniguchi, Cullen M.

AU - Skibber, John

AU - Ludmir, Ethan B.

AU - You, Y. Nancy

AU - Smith, Grace Li

AU - Bednarski, Brian

AU - Kostousov, Larisa

AU - Koay, Eugene J.

AU - Minsky, Bruce D.

AU - Tillman, Matthew

AU - Portier, Shaelynn

AU - Eng, Cathy

AU - Koong, Albert C.

AU - Chang, George J.

AU - Foo, Wai Chin

AU - Wang, Jing

AU - Soto, Luisa Solis

AU - Morris, Van K.

PY - 2023/3

Y1 - 2023/3

N2 - The identification of transcriptomic and protein biomarkers prognosticating recurrence risk after chemoradiation of localized squamous cell carcinoma of the anus (SCCA) has been limited by a lack of available fresh tissue at initial presentation. We analyzed archival FFPE SCCA specimens from pretreatment biopsies prior to chemoradiation for protein and RNA biomarkers from patients with localized SCCA who recurred (N = 23) and who did not recur (N = 25). Tumor cells and the tumor microenvironment (TME) were analyzed separately to identify biomarkers with significantly different expression between the recurrent and non-recurrent groups. Recurrent patients had higher mean protein expression of FoxP3, MAPK-activation markers (BRAF, p38-MAPK) and PI3K/Akt activation (phospho-Akt) within the tumor regions. The TME was characterized by the higher protein expression of immune checkpoint biomarkers such as PD-1, OX40L and LAG3. For patients with recurrent SCCA, the higher mean protein expression of fibronectin was observed in the tumor and TME compartments. No significant differences in RNA expression were observed. The higher baseline expression of immune checkpoint biomarkers, together with markers of MAPK and PI3K/Akt signaling, are associated with recurrence following chemoradiation for patients with localized SCCA. These data provide a rationale towards the application of immune-based therapeutic strategies to improve curative-intent outcomes beyond conventional therapies for patients with SCCA.

AB - The identification of transcriptomic and protein biomarkers prognosticating recurrence risk after chemoradiation of localized squamous cell carcinoma of the anus (SCCA) has been limited by a lack of available fresh tissue at initial presentation. We analyzed archival FFPE SCCA specimens from pretreatment biopsies prior to chemoradiation for protein and RNA biomarkers from patients with localized SCCA who recurred (N = 23) and who did not recur (N = 25). Tumor cells and the tumor microenvironment (TME) were analyzed separately to identify biomarkers with significantly different expression between the recurrent and non-recurrent groups. Recurrent patients had higher mean protein expression of FoxP3, MAPK-activation markers (BRAF, p38-MAPK) and PI3K/Akt activation (phospho-Akt) within the tumor regions. The TME was characterized by the higher protein expression of immune checkpoint biomarkers such as PD-1, OX40L and LAG3. For patients with recurrent SCCA, the higher mean protein expression of fibronectin was observed in the tumor and TME compartments. No significant differences in RNA expression were observed. The higher baseline expression of immune checkpoint biomarkers, together with markers of MAPK and PI3K/Akt signaling, are associated with recurrence following chemoradiation for patients with localized SCCA. These data provide a rationale towards the application of immune-based therapeutic strategies to improve curative-intent outcomes beyond conventional therapies for patients with SCCA.

KW - chemoradiation

KW - digital spatial profiling

KW - protein profiling

KW - recurrence

KW - squamous anal cell carcinoma

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UR - http://www.scopus.com/inward/citedby.url?scp=85151717176&partnerID=8YFLogxK

U2 - 10.3390/cancers15061701

DO - 10.3390/cancers15061701

M3 - Article

C2 - 36980587

AN - SCOPUS:85151717176

SN - 2072-6694

VL - 15

JO - Cancers

JF - Cancers

IS - 6

M1 - 1701

ER -

Differential Spatial Gene and Protein Expression Associated with Recurrence Following Chemoradiation for Localized Anal Squamous Cell Cancer

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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